MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

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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.

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

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.

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.

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

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

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Uchiyama Masateru

2012-03-01

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

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

Cardiac allograft immune activation: current perspectives

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Chang D

2014-12-01

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

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

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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.

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...

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

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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

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.

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.

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

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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.

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

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

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

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’...

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.

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.

[Combined assay of soluble CD30 and hepatocyte growth factor for diagnosis of acute renal allograft rejection].

Science.gov (United States)

Li, Chuan-jiang; Yu, Li-xin; Xu, Jian; Fu, Shao-jie; Deng, Wen-feng; Du, Chuan-fu; Wang, Yi-bin

2008-02-01

To study the value of detection of both preoperative soluble CD30 (sCD30) and hepatocyte growth factor (HGF) level 5 days after transplantation in the diagnosis of acute rejection of renal allograft. Preoperative serum sCD30 levels and HGF level 5 days after transplantation were determined in 65 renal-transplant recipients using enzyme-linked immunosorbent assay. The recipients were divided according to the sCD30 levels positivity. Receiver operating characteristic (ROC) curves were used to assess the value of HGF level on day 5 posttransplantation for diagnosis of acute renal allograft rejection, and the value of combined assay of the sCD30 and HGF levels was also estimated. After transplantation, 26 recipients developed graft rejection and 39 had uneventful recovery without rejection. With the cut-off value of sCD30 of 120 U/ml, the positivity rate of sCD30 was significantly higher in recipients with graft rejection than in those without (61.5% vs 17.9%, Pacute rejection showed also significantly higher HGF levels on day 5 posttransplantation than those without rejection (Pacute renal allograft rejection, and at the cut-off value of 90 ug/L, the diagnostic sensitivity was 84.6% and specificity 76.9%. Evaluation of both the sCD30 and HGF levels significantly enhanced the diagnostic accuracy of acute graft rejection. Combined assay of serum sCD30 and HGF levels offers a useful means for diagnosis of acute renal allograft rejection.

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

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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

Acute Hepatic Allograft Rejection in Pediatric Recipients: Effective Factors.

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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.

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

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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.

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

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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.

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.

A model of acute renal allograft rejection in outbred Yorkshire piglets.

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Lassiter, Randi; Wang, Youli; Fang, Xuexiu; Winn, Matt; Ghaffari, Arina; Ho, Chak-Sum; Helman, Sandra; Jajosky, Ryan; Kleven, Daniel; Stanley Nahman, N; Merchen, Todd D

2017-06-01

Pigs represent a desirable animal model for the study of rejection in kidney transplantation with inbred Yucatan miniature swine (YMS) the most commonly studied strain due to well defined swine leukocyte antigen (SLA) genotypes. However, limitations to YMS may include cost and availability. Outbred Yorkshire pigs are widely available and significantly cheaper than YMS. Recent advances in SLA genotyping have allowed its application to outbred strains. On this basis, we theorized that Yorkshire pigs would be a viable alternative to YMS for the study of rejection in kidney transplantation. To address this question, we performed auto (Auto) and allotransplants (Allo) in 24 Yorkshire pigs, and assessed SLA genotypes and acute rejection after 72h. At sacrifice, and when compared to autotransplants, allotransplants had significant elevations in serum creatinine (8.4±1.3 vs 2.8±2.0mg/dL for Allo vs autotransplants, respectively) and BUN (61±9 vs 19.2±15mg/dL for Allo vs autotransplants, respectively). Warm ischemia times between the two groups did not differ (24±2.3 vs 26.4±1.4min for Auto vs Allo, respectively). There were 16 distinct SLA haplotypes identified from pigs undergoing allotransplantion, no matched donor-recipient pairs, and all allografts demonstrated rejection. Type IIA cellular rejection (Banff) was the most common. One allograft demonstrated hyperacute rejection due a blood group incompatibility. Histologically, the expression of regulatory Tcells and dendritic cells was increased in allografts. These data suggest that Yorkshire pigs may be a useful model for the study of acute rejection in experimental kidney transplantation. Copyright © 2017. Published by Elsevier B.V.

Acute and chronic rejection: compartmentalization and kinetics of counterbalancing signals in cardiac transplants.

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Kaul, A M K; Goparaju, S; Dvorina, N; Iida, S; Keslar, K S; de la Motte, C A; Valujskikh, A; Fairchild, R L; Baldwin, W M

2015-02-01

Acute and chronic rejection impact distinct compartments of cardiac allografts. Intramyocardial mononuclear cell infiltrates define acute rejection, whereas chronic rejection affects large arteries. Hearts transplanted from male to female C57BL/6 mice undergo acute rejection with interstitial infiltrates at 2 weeks that resolve by 6 weeks when large arteries develop arteriopathy. These processes are dependent on T cells because no infiltrates developed in T cell-deficient mice and transfer of CD4 T cells restored T cell as well as macrophage infiltrates and ultimately neointima formation. Markers of inflammatory macrophages were up-regulated in the interstitium acutely and decreased as markers of wound healing macrophages increased chronically. Programmed cell death protein, a negative costimulator, and its ligand PDL1 were up-regulated in the interstitium during resolution of acute rejection. Blocking PDL1:PD1 interactions in the acute phase increased interstitial T cell infiltrates. Toll-like receptor (TLR) 4 and its endogenous ligand hyaluronan were increased in arteries with neointimal expansion. Injection of hyaluronan fragments increased intragraft production of chemokines. Our data indicate that negative costimulatory pathways are critical for the resolution of acute interstitial infiltrates. In the arterial compartment recognition of endogenous ligands including hyaluronan by the innate TLRs may support the progression of arteriopathy. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

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

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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

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.).

Functional Outcomes and Return to Sports After Acute Repair, Chronic Repair, and Allograft Reconstruction for Proximal Hamstring Ruptures.

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Rust, David A; Giveans, M Russell; Stone, Rebecca M; Samuelson, Kathryn M; Larson, Christopher M

2014-06-01

There are limited data regarding outcomes and return to sports after surgery for acute versus chronic proximal hamstring ruptures. Surgery for chronic proximal hamstring ruptures leads to improved outcomes and return to sports but at a lower level than with acute repair. Proximal hamstring reconstruction with an Achilles allograft for chronic ruptures is successful when direct repair is not possible. Cohort study; Level of evidence, 3. Between 2002 and 2012, a total of 72 patients with a traumatic proximal hamstring rupture (51 acute, 21 chronic) underwent either direct tendon repair with suture anchors (n = 58) or Achilles allograft tendon reconstruction (n = 14). Results from the Single Assessment Numeric Evaluation (SANE) for activities of daily living (ADL) and sports-related activities, Short Form-12 (SF-12), visual analog scale (VAS), and a patient satisfaction questionnaire were obtained. The mean time to surgery in the chronic group was 441.4 days versus 17.8 days in the acute group. At a mean follow-up of 45 months, patients with chronic tears had inferior sports activity scores (70.2% vs 80.3%, respectively; P = .026) and a trend for decreased ADL scores (86.5% vs 93.3%, respectively; P = .085) compared with those with acute tears. Patients with chronic tears, however, reported significant improvements postoperatively for both sports activity scores (30.3% to 70.2%; P sports activity scores equal to those of chronic repair (P = .507 and P = .904, respectively). There were no significant differences between groups in SF-12, VAS, or patient satisfaction outcomes (mean, 85.2% satisfaction overall). Acute repair was superior to chronic surgery with regard to return to sports. Acute and chronic proximal hamstring repair and allograft reconstruction had favorable results for ADL. For low-demand patients or those with medical comorbidities, delayed repair or reconstruction might be considered with an expected 87% return to normal ADL. For patients who desire to

Acute leukaemoid reaction following cardiac surgery

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Webb Stephen T

2007-01-01

Full Text Available Abstract Chronic myelomonocytic leukaemia is an atypical myeloproliferative disorder with a natural history of progression to acute myeloid leukaemia, a complex and poorly understood response by the bone marrow to stress. Cardiac surgery activates many inflammatory cascades and may precipitate a systemic inflammatory response syndrome. We present a case of undiagnosed chronic myelomonocytic leukaemia who developed rapidly fatal multi-organ dysfunction following cardiac surgery due to an acute leukaemoid reaction.

A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

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Faikah Gueler

Full Text Available Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx. In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV, might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days was initiated 24 hours after IRI when acute kidney injury (AKI was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF and glomerular filtration rate (GFR at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

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Peter Moritz Becher

2017-01-01

Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

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

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

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

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

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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.

Pulsed-wave transmitral Doppler do not diagnose moderate acute rejection after heart transplantation

NARCIS (Netherlands)

Mannaerts, H. F.; Simoons, M. L.; Balk, A. H.; Tijssen, J.; van der Borden, S. G.; Zondervan, P. E.; Mochtar, B.; Weimar, W.; Roelandt, J. R.

1993-01-01

The value of pulsed-wave transmitral Doppler for the diagnosis of moderate acute rejection was examined in a total of 347 Doppler recordings obtained in 32 consecutive cardiac allograft recipients. Serial Doppler examinations (median, 11 per patient; range, 1 to 23) were performed simultaneously

PULSED-WAVE TRANSMITRAL DOPPLER DO NOT DIAGNOSE MODERATE ACUTE REJECTION AFTER HEART-TRANSPLANTATION

NARCIS (Netherlands)

MANNAERTS, HF; SIMOONS, ML; BALK, AH; TIJSSEN, J; VANDERBORDEN, SG; ZONDERVAN, PE; MOCHTAR, B; WEIMAR, W; ROELANDT, [No Value

1993-01-01

The value of pulsed-wave transmitral Doppler for the diagnosis of moderate acute rejection was examined in a total of 347 Doppler recordings obtained in 32 consecutive cardiac allograft recipients. Serial Doppler examinations (median, 11 per patient; range, 1 to 23) were performed simultaneously

Emergency room thoracotomy for acute traumatic cardiac tamponade caused by a blunt cardiac injury: A case report

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Kenichiro Ishida

2017-01-01

Conclusion: A prompt diagnosis using FAST and treatment can be lifesaving in traumatic acute cardiac tamponade. A pericardiotomy via a thoracotomy is mandatory for lifesaving cardiac decompression in acute traumatic cardiac tamponade in cases of ineffective drainage due to clot formation within the pericardial space.

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.

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.)

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...

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

Acute cardiac failure in neuroleptic malignant syndrome.

LENUS (Irish Health Repository)

Sparrow, Patrick

2012-02-03

We present a case of rapid onset acute cardiac failure developing as part of neuroleptic malignant syndrome in a 35-year-old woman following treatment with thioridazine and lithium. Post mortem histology of cardiac and skeletal muscle showed similar changes of focal cellular necrosis and vacuolation suggesting a common disease process.

[Acute cardiac failure in pheochromocytoma.

DEFF Research Database (Denmark)

Jønler, Morten; Munk, Kim

2008-01-01

Pheochromocytoma (P) is an endocrine catecholamine-secreting tumor. Classical symptoms like hypertension, attacks of sweating, palpitations, headache and palor are related to catecholamine discharge. We provide a case of P in a 71 year-old man presenting with acute cardiac failure, severe reduction...

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.

Octogenarians' post-acute care use after cardiac valve surgery and recovery: clinical implications.

Science.gov (United States)

Edmiston, Elizabeth; Dolansky, Mary A; Zullo, Melissa; Forman, Daniel E

2017-12-21

Octogenarians receiving cardiac valve surgery is increasing and recovery is challenging. Post-acute care (PAC) services assist with recovery, yet services provided in facilities do not provide adequate cardiac-focused care or long-term self-management support. The purpose of the paper was to report post-acute care discharge rates in octogenarians and propose clinical implications to improve PAC services. Using a 2003 Medicare Part A database, we studied post-acute care service use in octogenarians after cardiac valve surgery. We propose expansion of the Geriatric Cardiac Care model to include broader clinical therapy dynamics. The sample (n = 10,062) included patients over 80 years discharged from acute care following valve surgery. Post-acute care services were used by 68% of octagarians following cardiac valve surgery (1% intermediate rehabilitation, 35% skilled nursing facility, 32% home health). The large percentage of octagarians using PAC point to the importance of integrating geriatric cardiac care into post-acute services to optimize recovery outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiac computed tomography in patients with acute coronary syndrome

International Nuclear Information System (INIS)

Schlett, C.L.; Bamberg, F.

2014-01-01

Currently, cardiac computed tomography (CT) is increasingly being implemented into clinical algorithms, primarily due to substantial technical advances over the last decade. Its use in the setting of suspected acute coronary syndrome is of particular relevance, given the high degree of accumulating scientific evidence of improving patient outcomes. Performing cardiac CT requires specific knowledge on the available scan acquisitions and patient preparation. Also, expertise is required in order to interpret the coronary and extra-coronary findings adequately. The present article provides an overview of the different aspects on the use of cardiac CT in the setting of acute coronary syndrome.

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

Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation

Directory of Open Access Journals (Sweden)

Dai Yong

2008-01-01

Full Text Available At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved if rapid, noninvasive and reliable biomarkers of rejection were available. This study is designed to determine whether such protein biomarkers can be found in renal-graft tissue proteomic approach. Orthotopic kidney transplantations were performed using Fisher (F344 or Lewis rats as donors and Lewis rats as recipients. Hence, there were two groups of renal transplant models: one is allograft (from F344 to Lewis rats; another is syngrafts (from Lewis to Lewis rats serving as control. Renal tissues were collected 3, 7 and 14 days after transplantation. As many as 18 samples were analyzed by 2-D Electrophoresis and mass spectrometry (MALDI-TOF-TOF-MS. Eleven differentially expressed proteins were identified between groups. In conclusion, proteomic technology can detect renal tissue proteins associated with acute renal allograft rejection. Identification of these proteins as diagnostic markers for rejection in patients′ urine or sera may be useful and non-invasive, and these proteins might serve as novel therapeutic targets that also help to improve the understanding of mechanism of renal rejection.

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.

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

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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.)

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

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection.

Science.gov (United States)

Nafar, Mohsen; Farrokhi, Farhat; Vaezi, Mohammad; Entezari, Amir-Ebrahim; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Eniollahi, Behzad

2009-01-01

Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

Cardiac Arrythmias in Acute and Chronic Renal Failure

Directory of Open Access Journals (Sweden)

Ali A. Handjani

1966-01-01

Full Text Available Cardiac arrythmias are frequent complications in acute and chronic renal failure and they may well account for sudden unexplained death in these patients. Based upon our recent study, we strongly believe that among other causative factors, focal degeneration of myocardium is the commonest and the most potentially dangerous cause of cardiac arrythmias. We suggest in emergency instances, ouabain to be used instead of digitalis which appears to be quite safe with dramatic results in cardiac arrythmias of these group.

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.

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.

Posttransplant soluble CD30 as a predictor of acute renal allograft rejection.

Science.gov (United States)

Kamali, Koosha; Abbasi, Mohammad Amin; Farokhi, Babak; Abbasi, Ata; Fallah, Parvane; Seifee, Mohammad Hasan; Ghadimi, Naime; Rezaie, Alireza R

2009-12-01

Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. In this prospective study,we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. Preoperative sCD30 levels of 3 groups were 96.2 -/+ 32.5, 80.2 -/+ 28.3, and 76.8 -/+ 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 -/+ 5.2, 22.1 -/+ 3.2, and 19.8 -/+ 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period.

Plasma levels of soluble CD30 in kidney graft recipients as predictors of acute allograft rejection.

Science.gov (United States)

Ayed, K; Abdallah, T B; Bardi, R; Abderrahim, E; Kheder, A

2006-09-01

In renal transplant recipients elevated soluble serum CD30 levels are associated with increased rejection and graft loss. We sought to determine the sCD30 plasma levels before and after kidney transplantation and to assess whether sCD30 was a predictive factor of immunological risk. sCD30 plasma levels were determined by an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before as well as 7, 15, and 21 days after transplantation. Eighteen patients developed acute allograft rejection (group I) and 34 patients showed uneventful courses (group II). Before transplantation sCD30 plasma levels were elevated in both groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients with acute rejection showed higher relative levels of plasma sCD30 on days 7 and 15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a difference that was significant for group I (P = .0003) and not significant for group II (P = .09). On day 21, sCD30 decreased in the two groups but remained higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed acute rejection only (26.4%), a difference that was not significant (P > .05). If we consider 100 U/mL as the minimum predictive level for allograft rejection, our results suggested that levels of sCD30 should be taken into consideration with the presence of HLA-antibodies detectable before and after transplantation, especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 sCD30 is a useful procedure for the recognition of rejection in its earliest stages.

Radioimmunoassay of human cardiac tropomyosin in acute myocardial infarction

International Nuclear Information System (INIS)

Cummins, P.; McGurk, B.; Littler, W.A.

1981-01-01

Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac 125 I-labelled tropomyosin in human sera down to levels of 1 ng/ml. Values for human cardiac tropomyosin in normal patients ranged from less than 1 to 3 ng/ml. In 18 patients with acute myocardial infarction all had elevated tropomyosin levels ranging from 41 to above 200 ng/ml with a mean peak level of 101 ng/ml. In this study there were no false positive or false negative results. In the initial stages of infarction the time course of appearance and peak levels of cardiac tropomyosin, total creatine kinase and creatine kinase MB isoenzyme were similar. Although total creatine kinase and creatine kinase MB isoenzyme levels were normal after 72 h in patients with single, uncomplicated infarction, cardiac tropomyosin levels were still significantly elevated above normal after this time, being 30-60% of peak values. Radioimmunoassay of human cardiac tropomyosin may prove useful in the diagnosis and in the management of patients with acute myocardial infarction, particularly in the long-term postinfarction period. (author)

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

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.

HEart trAnsplantation Registry of piTie-Salpetriere University Hospital

Science.gov (United States)

2018-01-08

Cardiac Transplant Disorder; Cardiac Death; Heart Failure; Acute Cellular Graft Rejection; Antibody-Mediated Graft Rejection; Cardiac Allograft Vasculopathy; Heart Transplant Rejection; Immune Tolerance

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.

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

Sudden cardiac death and acute pathology of coronary arteries

NARCIS (Netherlands)

van Dantzig, J. M.; Becker, A. E.

1986-01-01

The pathology of sudden cardiac death still is a matter of controversy, particularly with respect to the state of the coronary arteries. A recent study has shown a high incidence of acute lesions and suggests a causal relationship. The present study has been designed to verify whether or not acute

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.

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

Cardiac Myosin Binding Protein-C Autoantibodies Are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome

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Thomas L. Lynch, IVPhD

2017-04-01

Full Text Available Summary: The degradation and release of cardiac myosin binding protein-C (cMyBP-C upon cardiac damage may stimulate an inflammatory response and autoantibody (AAb production. We determined whether the presence of cMyBP-C-AAbs associated with adverse cardiac function in cardiovascular disease patients. Importantly, cMyBP-C-AAbs were significantly detected in acute coronary syndrome patient sera upon arrival to the emergency department, particularly in ST-segment elevation myocardial infarction patients. Patients positive for cMyBP-C-AAbs had reduced left ventricular ejection fraction and elevated levels of clinical biomarkers of myocardial infarction. We conclude that cMyBP-C-AAbs may serve as early predictive indicators of deteriorating cardiac function and patient outcome in acute coronary syndrome patients prior to the infarction. Key Words: acute myocardial infarction, autoantibodies, cardiac myosin binding protein-c, cardiomyopathy

Proteomic profiling of renal allograft rejection in serum using magnetic bead-based sample fractionation and MALDI-TOF MS.

Science.gov (United States)

Sui, Weiguo; Huang, Liling; Dai, Yong; Chen, Jiejing; Yan, Qiang; Huang, He

2010-12-01

Proteomics is one of the emerging techniques for biomarker discovery. Biomarkers can be used for early noninvasive diagnosis and prognosis of diseases and treatment efficacy evaluation. In the present study, the well-established research systems of ClinProt Micro solution incorporated unique magnetic bead sample preparation technology, which, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), have become very successful in bioinformatics due to its outstanding performance and reproducibility for discovery disease-related biomarker. We collected fasting blood samples from patients with biopsy-confirmed acute renal allograft rejection (n = 12), chronic rejection (n = 12), stable graft function (n = 12) and also from healthy volunteers (n = 13) to study serum peptidome patterns. Specimens were purified with magnetic bead-based weak cation exchange chromatography and analyzed with a MALDI-TOF mass spectrometer. The results indicated that 18 differential peptide peaks were selected as potential biomarkers of acute renal allograft rejection, and 6 differential peptide peaks were selected as potential biomarkers of chronic rejection. A Quick Classifier Algorithm was used to set up the classification models for acute and chronic renal allograft rejection. The algorithm models recognize 82.64% of acute rejection and 98.96% of chronic rejection episodes, respectively. We were able to identify serum protein fingerprints in small sample sizes of recipients with renal allograft rejection and establish the models for diagnosis of renal allograft rejection. This preliminary study demonstrated that proteomics is an emerging tool for early diagnosis of renal allograft rejection and helps us to better understand the pathogenesis of disease process.

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

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

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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.)

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.)

Serum cardiac troponin I in acute stroke is related to serum cortisol and TNF-alpha

DEFF Research Database (Denmark)

Christensen, Hanne Krarup; Johannesen, Helle Hjorth; Christensen, Anders Fogh

2004-01-01

Serum cardiac troponin I (cTnI) is a specific marker of myocardial injury related to in-patient fatality and cardiac injury in acute stroke. We investigated whether cTnI in acute stroke is related to serum cortisol, acute inflammatory response, and insular damage. We also investigated whether c...

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.

Hypertrophic Cardiomyopathy Mimicking Acute Anterior Myocardial Infarction Associated with Sudden Cardiac Death

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Y. Daralammouri

2012-01-01

Full Text Available Hypertrophic cardiomyopathy is the most common genetic disease of the heart. We report a rare case of hypertrophic obstructive cardiomyopathy mimicking an acute anterior myocardial infarction associated with sudden cardiac death. The patient presented with acute ST elevation myocardial infarction and significant elevation of cardiac enzymes. Cardiac catheterization showed some atherosclerotic coronary artery disease, without significant stenosis. Echocardiography showed left ventricular hypertrophy with a left ventricular outflow tract obstruction; the pressure gradient at rest was 20 mmHg and became severe with the Valsalva maneuver (100 mmHg. There was no family history of sudden cardiac death. Six days later, the patient suffered a syncope on his way to magnetic resonance imaging. He was successfully resuscitated by ventricular fibrillation.

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

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

Synergistic effects of Isatis tinctoria L. and tacrolimus in the prevention of acute heart rejection in mice.

Science.gov (United States)

Wang, Yongzhi; Qin, Qing; Chen, Jibing; Kuang, Xiaocong; Xia, Junjie; Xie, Baiyi; Wang, Feng; Liang, Hua; Qi, Zhongquan

2009-12-01

Although immunosuppressive treatments are available for acute cardiac rejection no viable treatment exists for long-term cardiac graft failure. Moreover, the extended use of calcineurin inhibitor immunosuppressants, the mainstay of current treatment for cardiac transplantation, leads to significant side effects such as nephrotoxicity and an increased risk of cardiac disease. Because some agents used in Traditional Chinese Medicine (TCM) have strong immunosuppressive effects coupled with low toxicity, we investigated the effect of Compound K (K), the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., either as a single treatment or combined with tacrolimus (FK-506) on acute cardiac allograft rejection. We compared the ability of K alone, or in combination with FK-506, to inhibit acute heart transplant rejection both in vitro and in vivo. We found that the inhibition of lymphocyte proliferation was positively correlated with K concentration. K significantly reduced IL-2 and IFN-gamma expression levels and significantly inhibited lymphocyte proliferation in both a lymphocyte transformation test and a mixed lymphocyte reaction (MLR). We also found that the inhibitory effect of a combination of K and a sub-therapeutic dose of FK-506 (SubFK-506) was stronger than that of full-dose FK-506 alone. Oral administration of K reduced acute cardiac allograft rejection in mice and had no apparent toxicity. In vivo, the immunosuppressive effect of K combined with a half-dose of FK-506 was equivalent to that of a full-dose of FK-506 alone. K combined with a half-dose of FK-506 reduced the expression levels of IL-2 and IFN-gamma (both within the graft and in the recipients' serum) more effectively than a full-dose of FK-506. These results show that K has significant immunosuppressive effects both in vitro and in vivo. When used as a combination therapy with FK-506 we see a powerful inhibition of rejection with no obvious toxic side effects. The

High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant.

Science.gov (United States)

Patel, Parag C; Hill, Douglas A; Ayers, Colby R; Lavingia, Bhavna; Kaiser, Patricia; Dyer, Adrian K; Barnes, Aliessa P; Thibodeau, Jennifer T; Mishkin, Joseph D; Mammen, Pradeep P A; Markham, David W; Stastny, Peter; Ring, W Steves; de Lemos, James A; Drazner, Mark H

2014-05-01

A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (P(trend)<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76-0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance. © 2014 American Heart Association, Inc.

Detection of acute renal allograft rejection by analysis of Renal TissueProteomics in rat models of renal transplantation

International Nuclear Information System (INIS)

Dai, Y.; Lv, T.; Wang, K.; Li, D.; Huang, Y.; Liu, J.

2008-01-01

At present, the diagnosis of renal allograft rejection requires a renalbiopsy. Clinical management of renal transplant patients would be improved ifrapid, noninvasive and reliable biomarkers of rejection were available. Thisstudy is designed to determine whether such protein biomarkers can be foundin renal graft tissue proteomic approach. Orthotopic kidney transplantationswere performed using Fisher (F344) or Lewis rats as donors and Lewis rats asrecipients. Hence, there were two groups of renal transplant models: one isallograft (from F344 to Lewis rats); another is syngrafts (from Lewis toLewis rats) serving as control. Renal tissues were collected 3, 7 and 14 daysafter transplantation. As many 18 samples were analyzed by 2-DElectrophoresis and mass spectrometry (MALDI-TOF-TOF-MS). Elevendifferentially expressed proteins were identified between groups. Inconclusion, proteomic technology can detect renal tissue proteins associatedwith acute renal allograft rejection. Identification of these proteins asdiagnostic markers for rejection in patient's urine or sera may be useful andnon-invasive, and these proteins might serve as novel therapeutic targetsthat also help to improve the understanding of mechanisms of renal rejection.(author)

Does overprotection cause cardiac invalidism after acute myocardial infarction?

Science.gov (United States)

Riegel, B J; Dracup, K A

1992-01-01

To determine if overprotection on the part of the patient's family and friends contributes to the development of cardiac invalidism after acute myocardial infarction. Longitudinal survey. Nine hospitals in the southwestern United States. One hundred eleven patients who had experienced a first acute myocardial infarction. Subjects were predominantly male, older-aged, married, caucasian, and in functional class I. Eighty-one patients characterized themselves as being overprotected (i.e., receiving more social support from family and friends than desired), and 28 reported receiving inadequate support. Only two patients reported receiving as much support as they desired. Self-esteem, emotional distress, health perceptions, interpersonal dependency, return to work. Overprotected patients experienced less anxiety, depression, anger, confusion, more vigor, and higher self-esteem than inadequately supported patients 1 month after myocardial infarction (p Overprotection on the part of family and friends may facilitate psychosocial adjustment in the early months after an acute myocardial infarction rather than lead to cardiac invalidism.

Prehospital behaviour of patients admitted with acute coronary syndrome or witnessed cardiac arrest

DEFF Research Database (Denmark)

Ottesen, Michael Mundt; Dixen, Ulrik; Torp-Pedersen, Christian

2003-01-01

OBJECTIVE: To study prehospital behaviour of patients admitted with acute coronary syndrome or witnessed cardiac arrest. DESIGN: Structured interview of 250 consecutive patients with acute coronary syndrome and relatives of 48 patients with witnessed cardiac arrest. The following courses of action...... hundred and thirteen patients (45%) knew of thrombolytic therapy. Twenty-seven of 75 patients with knowledge of the benefit of prompt treatment with thrombolysis, acted in accordance with this awareness. CONCLUSION: Patients misinterpret symptoms of acute coronary syndrome and are misguided when calling...

Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

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Yingchun Wang

2015-01-01

Full Text Available Sickle cell nephropathy (SCN is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI. Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+ was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2 rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

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.

Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

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Mingliang Li

Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

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.

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)

Prediction of acute renal allograft rejection in early post-transplantation period by soluble CD30.

Science.gov (United States)

Dong, Wang; Shunliang, Yang; Weizhen, Wu; Qinghua, Wang; Zhangxin, Zeng; Jianming, Tan; He, Wang

2006-06-01

To evaluate the feasibility of serum sCD30 for prediction of acute graft rejection, we analyzed clinical data of 231 patients, whose serum levels of sCD30 were detected by ELISA before and after transplantation. They were divided into three groups: acute rejection group (AR, n = 49), uncomplicated course group (UC, n = 171) and delayed graft function group (DGF, n = 11). Preoperative sCD30 levels of three groups were 183 +/- 74, 177 +/- 82 and 168 +/- 53 U/ml, respectively (P = 0.82). Significant decrease of sCD30 was detected in three groups on day 5 and 10 post-transplantation respectively (52 +/- 30 and 9 +/- 5 U/ml respectively, P sCD30 values on day 5 post-transplantation (92 +/- 27 U/ml vs. 41 +/- 20 U/ml and 48 +/- 18 U/ml, P sCD30 levels on day 10 post-transplantation were virtually similar in patients of three groups (P = 0.43). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 5 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 91.8%, sensitivity 87.1%). Measurement of soluble CD30 on day 5 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.

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

DEFF Research Database (Denmark)

Dankiewicz, J; Nielsen, N; Annborn, M

2015-01-01

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

Acute systemic inflammatory response after cardiac surgery in ...

African Journals Online (AJOL)

2017-09-03

Sep 3, 2017 ... valve(s) replacement were enrolled, from a single center hospital, after informed consent was obtained. C-reactive ... Cite as: Gojo MKE, Prakaschandra R. Acute systemic inflammatory response after cardiac surgery in patients infected with human im- ..... Arroyo-Espliguero R, Avanzas P, Cosín-Sales J, Al-.

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

Cardiac computed tomography in patients with acute coronary syndrome; Kardiale CT beim akuten Koronarsyndrom

Energy Technology Data Exchange (ETDEWEB)

Schlett, C.L. [Universitaetsklinikum, Heidelberg (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie; Alkadhi, H. [Universitaetsspital, Zuerich (Switzerland); Bamberg, F. [Universitaetsklinikum, Tuebingen (Germany). Diagnostische und Interventionelle Radiologie

2014-09-15

Currently, cardiac computed tomography (CT) is increasingly being implemented into clinical algorithms, primarily due to substantial technical advances over the last decade. Its use in the setting of suspected acute coronary syndrome is of particular relevance, given the high degree of accumulating scientific evidence of improving patient outcomes. Performing cardiac CT requires specific knowledge on the available scan acquisitions and patient preparation. Also, expertise is required in order to interpret the coronary and extra-coronary findings adequately. The present article provides an overview of the different aspects on the use of cardiac CT in the setting of acute coronary syndrome.

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.

Intragraft interleukin 2 mRNA expression during acute cellular rejection and left ventricular total wall thickness after heart transplantation

NARCIS (Netherlands)

de Groot-Kruseman, H A; Baan, C C; Hagman, E M; Mol, W M; Niesters, H G; Maat, A P; Zondervan, P E; Weimar, W; Balk, A H

OBJECTIVE: To assess whether diastolic graft function is influenced by intragraft interleukin 2 (IL-2) messenger RNA (mRNA) expression in rejecting cardiac allografts. DESIGN: 16 recipients of cardiac allografts were monitored during the first three months after transplantation. The presence of IL-2

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

Time to reach tacrolimus maximum blood concentration,mean residence time, and acute renal allograft rejection: an open-label, prospective, pharmacokinetic study in adult recipients.

Science.gov (United States)

Kuypers, Dirk R J; Vanrenterghem, Yves

2004-11-01

The aims of this study were to determine whether disposition-related pharmacokinetic parameters such as T(max) and mean residence time (MRT) could be used as predictors of clinical efficacy of tacrolimus in renal transplant recipients, and to what extent these parameters would be influenced by clinical variables. We previously demonstrated, in a prospective pharmacokinetic study in de novo renal allograft recipients, that patients who experienced early acute rejection did not differ from patients free from rejection in terms of tacrolimus pharmacokinetic exposure parameters (dose interval AUC, preadministration trough blood concentration, C(max), dose). However, recipients with acute rejection reached mean (SD) tacrolimus T(max) significantly faster than those who were free from rejection (0.96 [0.56] hour vs 1.77 [1.06] hours; P clearance nor T(1/2) could explain this unusual finding, we used data from the previous study to calculate MRT from the concentration-time curves. As part of the previous study, 100 patients (59 male, 41 female; mean [SD] age, 51.4 [13.8] years;age range, 20-75 years) were enrolled in the study The calculated MRT was significantly shorter in recipients with acute allograft rejection (11.32 [031] hours vs 11.52 [028] hours; P = 0.02), just like T(max) was an independent risk factor for acute rejection in a multivariate logistic regression model (odds ratio, 0.092 [95% CI, 0.014-0.629]; P = 0.01). Analyzing the impact of demographic, transplantation-related, and biochemical variables on MRT, we found that increasing serum albumin and hematocrit concentrations were associated with a prolonged MRT (P calculated MRT were associated with a higher incidence of early acute graft rejection. These findings suggest that a shorter transit time of tacrolimus in certain tissue compartments, rather than failure to obtain a maximum absolute tacrolimus blood concentration, might lead to inadequate immunosuppression early after transplantation.

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.

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

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

Acute thyrotoxicosis secondary to destructive thyroiditis associated with cardiac catheterization contrast dye.

Science.gov (United States)

Calvi, Laura; Daniels, Gilbert H

2011-04-01

Thyrotoxicosis caused by destructive thyroiditis is self-limited and results from the subacute release of preformed thyroid hormone. Common etiologies include painful subacute thyroiditis and silent (painless) subacute thyroiditis (including postpartum thyroiditis, amiodarone-associated destructive thyroiditis, and lithium-associated thyroiditis). Thyrotoxicosis commonly evolves slowly over a matter of weeks. We report a unique case of severe thyrotoxicosis caused by acute- onset painful destructive thyroiditis in a patient who received large amounts of nonionic contrast dye Hexabrix® for cardiac catheterization. The results of thyroid function and physical examination were normal before the catheterization. The acute onset of severe thyroid pain, rapid increase in serum Free Thyroxine Index, and thyroglobulin concentrations with a triiodothyronine to free thyroxine index ratio of thyroiditis, likely related to direct toxicity from the iodinated contrast material. In light of the large number of patients who receive these contrast agents during cardiac catheterization, clinicians should be advised of this potentially serious complication, particularly in the setting of unstable cardiac disease.

Does Cardiac Rehabilitation After an Acute Cardiac Syndrome Lead to Changes in Physical Activity Habits? Systematic Review

NARCIS (Netherlands)

ter Hoeve, Nienke; Huisstede, Bionka M. A.; Stam, Henk J.; van Domburg, Ron T.; Sunamura, Madoka; van den Berg-Emons, Rita J. G.

Background. Optimal physical activity levels have health benefits for patients with acute coronary syndrome (ACS) and are an important goal of cardiac rehabilitation (CR). Purpose. The purpose of this study was to systematically review literature regarding short-term effects (= 6 months after

Cardiac rehabilitation following an acute coronary syndrome: Trends in referral, predictors and mortality outcome in a multicenter national registry between years 2006-2013: Report from the Working Group on Cardiac Rehabilitation, the Israeli Heart Society.

Science.gov (United States)

Chernomordik, Fernando; Sabbag, Avi; Tzur, Boaz; Kopel, Eran; Goldkorn, Ronen; Matetzky, Shlomi; Goldenberg, Ilan; Shlomo, Nir; Klempfner, Robert

2017-01-01

Background Utilization of cardiac rehabilitation is suboptimal. The aim of the study was to assess referral trends over the past decade, to identify predictors for referral to a cardiac rehabilitation program, and to evaluate the association with one-year mortality in a large national registry of acute coronary syndrome patients. Design and methods Data were extracted from the Acute Coronary Syndrome Israeli Survey national surveys between 2006-2013. A total of 6551 patients discharged with a diagnosis of acute coronary syndrome were included. Results Referral to cardiac rehabilitation following an acute coronary syndrome increased from 38% in 2006 to 57% in 2013 ( p for trend acute coronary syndrome. However, cardiac rehabilitation is still under-utilized in important high-risk subsets of this population. Patients referred to cardiac rehabilitation have a lower adjusted mortality risk.

Influence of the timing of cardiac catheterization and amount of contrast media on acute renal failure after cardiac surgery

Directory of Open Access Journals (Sweden)

Mohsen Mirmohammad Sadeghi

2011-01-01

Full Text Available Background: There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF. Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated. Methods: Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression. Results: The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05. Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57% and 6 (52.17% after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002, followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009 and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031. Conclusions: Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have

Influence of the timing of cardiac catheterization and amount of contrast media on acute renal failure after cardiac surgery.

Science.gov (United States)

Sadeghi, Mohsen Mirmohammad; Gharipour, Mojgan; Nilforoush, Peiman; Shamsolkotabi, Hamid; Sadeghi, Hamid Mirmohammad; Kiani, Amjad; Sadeghi, Pouya Mirmohammad; Farahmand, Niloufar

2011-04-01

There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF). Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated. Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression. The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05). Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57%) and 6 (52.17%) after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002), followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009) and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031). Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have this protective effect.

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.

Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

Directory of Open Access Journals (Sweden)

Kapka Miteva

Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

Cardiac Auscultation for Noncardiologists: Application in Cardiac Rehabilitation Programs: PART I: PATIENTS AFTER ACUTE CORONARY SYNDROMES AND HEART FAILURE.

Science.gov (United States)

Compostella, Leonida; Compostella, Caterina; Russo, Nicola; Setzu, Tiziana; Iliceto, Sabino; Bellotto, Fabio

2017-09-01

During outpatient cardiac rehabilitation after an acute coronary syndrome or after an episode of congestive heart failure, a careful, periodic evaluation of patients' clinical and hemodynamic status is essential. Simple and traditional cardiac auscultation could play a role in providing useful prognostic information.Reduced intensity of the first heart sound (S1), especially when associated with prolonged apical impulse and the appearance of added sounds, may help identify left ventricular (LV) dysfunction or conduction disturbances, sometimes associated with transient myocardial ischemia. If both S1 and second heart sound (S2) are reduced in intensity, a pericardial effusion may be suspected, whereas an increased intensity of S2 may indicate increased pulmonary artery pressure. The persistence of a protodiastolic sound (S3) after an acute coronary syndrome is an indicator of severe LV dysfunction and a poor prognosis. In patients with congestive heart failure, the association of an S3 and elevated heart rate may indicate impending decompensation. A presystolic sound (S4) is often associated with S3 in patients with LV failure, although it could also be present in hypertensive patients and in patients with an LV aneurysm. Careful evaluation of apical systolic murmurs could help identifying possible LV dysfunction or mitral valve pathology, and differentiate them from a ruptured papillary muscle or ventricular septal rupture. Friction rubs after an acute myocardial infarction, due to reactive pericarditis or Dressler syndrome, are often associated with a complicated clinical course.During cardiac rehabilitation, periodic cardiac auscultation may provide useful information about the clinical-hemodynamic status of patients and allow timely detection of signs, heralding possible complications in an efficient and low-cost manner.

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.)

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

Cardiac-surgery associated acute kidney injury requiring renal replacement therapy. A Spanish retrospective case-cohort study

Directory of Open Access Journals (Sweden)

Garcia-Fernandez Nuria

2009-09-01

Full Text Available Abstract Background Acute kidney injury is among the most serious complications after cardiac surgery and is associated with an impaired outcome. Multiple factors may concur in the development of this disease. Moreover, severe renal failure requiring renal replacement therapy (RRT presents a high mortality rate. Consequently, we studied a Spanish cohort of patients to assess the risk factors for RRT in cardiac surgery-associated acute kidney injury (CSA-AKI. Methods A retrospective case-cohort study in 24 Spanish hospitals. All cases of RRT after cardiac surgery in 2007 were matched in a crude ratio of 1:4 consecutive patients based on age, sex, treated in the same year, at the same hospital and by the same group of surgeons. Results We analyzed the data from 864 patients enrolled in 2007. In multivariate analysis, severe acute kidney injury requiring postoperative RRT was significantly associated with the following variables: lower glomerular filtration rates, less basal haemoglobin, lower left ventricular ejection fraction, diabetes, prior diuretic treatment, urgent surgery, longer aortic cross clamp times, intraoperative administration of aprotinin, and increased number of packed red blood cells (PRBC transfused. When we conducted a propensity analysis using best-matched of 137 available pairs of patients, prior diuretic treatment, longer aortic cross clamp times and number of PRBC transfused were significantly associated with CSA-AKI. Patients requiring RRT needed longer hospital stays, and suffered higher mortality rates. Conclusion Cardiac-surgery associated acute kidney injury requiring RRT is associated with worse outcomes. For this reason, modifiable risk factors should be optimised and higher risk patients for acute kidney injury should be identified before undertaking cardiac surgery.

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.

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...

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.

Dioxin-induced acute cardiac mitochondrial oxidative damage and increased activity of ATP-sensitive potassium channels in Wistar rats

International Nuclear Information System (INIS)

Pereira, Susana P.; Pereira, Gonçalo C.; Pereira, Cláudia V.; Carvalho, Filipa S.; Cordeiro, Marília H.; Mota, Paula C.; Ramalho-Santos, João; Moreno, António J.; Oliveira, Paulo J.

2013-01-01

The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent. We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 μg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure. -- Highlights: •Acute TCDD treatment of Wistar rats causes cardiac oxidative stress. •Acute TCDD treatment causes cardiac mitochondrial alterations. •Mitochondrial liver vs. heart alterations are distinct. •TCDD treatment resulted in altered activity of cardiac mitochondrial K-ATP channels. -- Dioxin alters the regulation of cardiac mitochondrial ATP-sensitive potassium channels and disturbs mitochondrial physiology

A higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients' CD8 T cells.

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Laurence Ordonez

Full Text Available Although transplantation is the common treatment for end-stage renal failure, allograft rejection and marked morbidity from the use of immunosuppressive drugs remain important limitations. A major challenge in the field is to identify easy, reliable and noninvasive biomarkers allowing the prediction of deleterious alloreactive immune responses and the tailoring of immunosuppressive therapy in individuals according to the rejection risk. In this study, we first established that the expression of the RC isoform of the CD45 molecule (CD45RC on CD4 and CD8 T cells from healthy individuals identifies functionally distinct alloreactive T cell subsets that behave differently in terms of proliferation and cytokine secretion. We then investigated whether the frequency of the recipients CD45RC T cell subsets before transplantation would predict acute graft rejection in a cohort of 89 patients who had undergone their first kidney transplantation. We showed that patients exhibiting more than 54.7% of CD8 CD45RC(high T cells before transplantation had a 6 fold increased risk of acute kidney graft rejection. In contrast, the proportions of CD4 CD45RC T cells were not predictive. Thus, a higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients' CD8 T cells.

Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

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Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

2015-01-01

Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

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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

Rapid Rule-Out of Acute Myocardial Injury Using a Single High-Sensitivity Cardiac Troponin I Measurement.

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Sandoval, Yader; Smith, Stephen W; Shah, Anoop S V; Anand, Atul; Chapman, Andrew R; Love, Sara A; Schulz, Karen; Cao, Jing; Mills, Nicholas L; Apple, Fred S

2017-01-01

Rapid rule-out strategies using high-sensitivity cardiac troponin assays are largely supported by studies performed outside the US in selected cohorts of patients with chest pain that are atypical of US practice, and focused exclusively on ruling out acute myocardial infarction (AMI), rather than acute myocardial injury, which is more common and associated with a poor prognosis. Prospective, observational study of consecutive patients presenting to emergency departments [derivation (n = 1647) and validation (n = 2198) cohorts], where high-sensitivity cardiac troponin I (hs-cTnI) was measured on clinical indication. The negative predictive value (NPV) and diagnostic sensitivity of an hs-cTnI concentration rules out acute myocardial injury, regardless of etiology, with an excellent NPV and diagnostic sensitivity, and identifies patients at minimal risk of AMI or cardiac death at 30 days. ClinicalTrials.gov Identifier: NCT02060760. © 2016 American Association for Clinical Chemistry.

Osteochondral allograft.

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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.

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

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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.

3D cardiac wall thickening assessment for acute myocardial infarction

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Khalid, A.; Chan, B. T.; Lim, E.; Liew, Y. M.

2017-06-01

Acute myocardial infarction (AMI) is the most severe form of coronary artery disease leading to localized myocardial injury and therefore irregularities in the cardiac wall contractility. Studies have found very limited differences in global indices (such as ejection fraction, myocardial mass and volume) between healthy subjects and AMI patients, and therefore suggested regional assessment. Regional index, specifically cardiac wall thickness (WT) and thickening is closely related to cardiac function and could reveal regional abnormality due to AMI. In this study, we developed a 3D wall thickening assessment method to identify regional wall contractility dysfunction due to localized myocardial injury from infarction. Wall thickness and thickening were assessed from 3D personalized cardiac models reconstructed from cine MRI images by fitting inscribed sphere between endocardial and epicardial wall. The thickening analysis was performed in 5 patients and 3 healthy subjects and the results were compared against the gold standard 2D late-gadolinium-enhanced (LGE) images for infarct localization. The notable finding of this study is the highly accurate estimation and visual representation of the infarct size and location in 3D. This study provides clinicians with an intuitive way to visually and qualitatively assess regional cardiac wall dysfunction due to infarction in AMI patients.

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

radiation treatment (median 4, range 1-22), number of transplants (one transplant in 77 %), and concomitant immunosuppressive therapy. Independent factors by the Cox regression model were: Sex (P=0.005), Creatinine levels (P=0.000), HLA-DR (P=0.05), PRA-Max > 70% (P=0.014). Each factor was scored using the integral coefficients to generate four different groups. 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 Kaplan-Meier survival analyzed by groups seems to produce an interpretable separation of the risk factors for graft loss. The number of rejections of pre-RT range from 1-6 (median 2) and post-RT range from 0-3 (median 0). Conclusions: Our experience indicates that radiation therapy provides effective treatment for acute refractory renal allograft rejection. The response to radiation therapy in patients treated with acute refractory renal graft rejection can be predicted by a new scoring system

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

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

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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.

Relative reductions in soluble CD30 levels post-transplant predict acute graft function in islet allograft recipients receiving three different immunosuppression protocols.

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Hire, Kelly; Hering, Bernhard; Bansal-Pakala, Pratima

2010-08-01

Despite advances in islet transplantation, challenges remain in monitoring for anti-islet immune responses. Soluble CD30 (sCD30) has been investigated as a predictor of acute rejection in kidney, lung, and heart transplantation as well as in a single study in human islet cell recipients. In this study, sCD30 levels were retrospectively assessed in 19 allograft recipients treated with three different immunosuppression induction therapies. Soluble CD30 levels were assessed at pre-transplant; early post-transplant (day 4-day 7); one-month post-transplant; and late post-transplant (day 90-day 120) and then correlated with eventual graft outcomes at 1-year follow-up. Results showed no correlation between mean serum sCD30 levels at any point in time pre- or post-transplant and graft function at 1-year follow-up. However, analysis demonstrated that mean sCD30 levels at day 28 or day 90-day 120 decreased from pre-transplant levels in recipients with long-term islet allograft function compared to recipients with partial or non-graft function (a decrease of 43.6+/-25.6% compared to 16.7+/-35.2%, psCD30 levels post-transplant overall. A larger reduction post-transplant correlated with full graft function. The results demonstrate that a relative reduction in sCD30 levels post-transplant may be applicable as a biomarker to monitor graft function in islet allograft recipients. Additionally, knowledge of the impact of various immunosuppression protocols on the timing and extent of changes in post-transplant sCD30 levels could aid in patient-specific tailoring of immunosuppression. Copyright © 2010 Elsevier B.V. All rights reserved.

Epstein-Barr Viral Infection in Renal Allograft Recipients: A Single Center Experience

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Zadeh Zakie

2006-01-01

Full Text Available In this study we attempted to identify the factors involved in Epstein-Barr viral (EBV infection among renal allograft recipients. We studied 68 renal allograft recipients hospitalized at the Imam Khomeini Medical Center from 2001 to 2004. Blood samples were obtained from the patients before renal transplantation and repeated every 3 months during the first year after transplantation. Enzyme linked immunosorbant assay (ELISA tests were performed on these samples to determine if antibodies to EBV antigens, such as viral capsid antigen(VCAIgM, VCAIgG or Epstein Barr neoantigen (EBNAIgG, were present. The types of prescribed immunosuppressive agents and the incidence of acute allograft rejection were closely observed to define their association with EBV. EBV infection developed in 58 (85.3 % patients and active disease in 10 (14.7%. EBV was detected in 40 (58.8% patients during the first year after transplantation. There was EBNAIgG seropositivity in 65 (95.6% patients before transplantation; this number increased to 68 (100 % after transplantation. In contrast, VCAIgG seropositivity increased from 92.6% before transplantation to 96.9% after transplantation; whereas VCAIgM seropositivity increased from 17.6% before transplantation to 58.8% after transplantation. There were no statistically significant differences in the reactivation of EBV infection between the different immunosuppressive regimens, between the groups of acute rejection and no acute rejection, or between the groups that received and did not receive anti-lymphocyte globulin (ALG We conclude that most EBV activation after transplantation may represent a secondary form of a preexisting infection and we could not find a clear association with a specific immunosuppressive regimen, including the use of ALG. Further investigation is thus required to elucidate the factors involved in the reactivation of the EBV infection in the transplant population.

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

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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.

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

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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

Application of Minicircle Technology of Self-Reproducing Synthetic Protein Drugs in Preventing Skin Allograft Rejection.

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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.

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

DEFF Research Database (Denmark)

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

2014-01-01

BACKGROUND: International guidelines recommend referral for cardiac rehabilitation (CR) after acute myocardial infarction (AMI). However, the impact on long-term survival after CR referral has not been adjusted by time-variance. We compared the effects of CR referral after hospitalization for AMI......% CI, 0.66 to 0.96, p = 0.02 in 2003) when patients entered the model at three months after discharge and had a common exit at 90 months. Significant positive and negative predictors for CR referral were beta-blocker prescription (+), reperfusion (+) and age (-) in 1995, and reperfusion...... (+), revascularization (+), heart failure (HF) (+), antiplatelets (+), angiotensin-converting-enzyme inhibitor (ACE-I) (+), statins (+), diabetes (-), and the modified Global Registry of Acute Cardiac Events (GRACE) risk score (-) in 2003. CONCLUSIONS: CR referral was associated with improved survival in 2003...

Magnetic resonance tomography of the heart

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Tscholakoff, D.

1987-01-01

In this experimental study (canine heart) a variety of pathologic conditions of the myocardium were studied using ECG-triggered magnetic resonance imaging (MRI). The purpose of this study was to examine the MR appearance and the T/sub 2/ relaxation times of occlusive and reperfused myocardial infarcts, of hypertrophic cardiomyopathy and of cardiac transplants with and without acute cardiac allograft rejection. MR images were correlated with the results of histology and tissue water content. MRI identified normal myocardium with T/sub 2/ values of 38 (+-4.3) msec. Myocardial infarcts and acute allograft rejection had significant (p<0.05) longer T/sub 2/ values compared to normal myocardium. On the basis of T/sub 2/ relaxation times no further differentiation among different pathologic entities was possible. Therefore, it is necessary to include morphologic criteria such as myocardial wall thickness, cardiac chamber size and intracavitary blood flow signal in the interpretation of cardiac MR tomograms.

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

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

Acute kidney injury is independently associated with higher mortality after cardiac surgery

DEFF Research Database (Denmark)

Kandler, Kristian; Jensen, Mathias E; Nilsson, Jens C

2014-01-01

OBJECTIVES: To investigate the incidence of acute kidney injury after cardiac surgery and its association with mortality in a patient population receiving ibuprofen and gentamicin perioperatively. DESIGN: Retrospective study with Cox regression analysis to control for possible preoperative......, intraoperative and postoperative confounders. SETTING: University hospital-based single-center study. PARTICIPANTS: All patients who underwent coronary artery bypass grafting ± valve surgery during 2012. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Acute surgery within 24 hours of coronary angiography.......21-4.51, p = 0.011) and 5.62 (95% CI: 2.42-13.06), psurgery developed AKI in this contemporary cohort. Furthermore, acute kidney injury was an independent...

Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

DEFF Research Database (Denmark)

Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi

2015-01-01

OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared...

Chronic resuscitation after trauma-hemorrhage and acute fluid replacement improves hepatocellular function and cardiac output.

Science.gov (United States)

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1998-01-01

To determine whether prolonged (chronic) resuscitation has any beneficial effects on cardiac output and hepatocellular function after trauma-hemorrhage and acute fluid replacement. Acute fluid resuscitation after trauma-hemorrhage restores but does not maintain the depressed hepatocellular function and cardiac output. Male Sprague-Dawley rats underwent a 5-cm laparotomy (i.e., trauma was induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer's lactate (RL). The animals were acutely resuscitated with RL using 4 times the volume of maximum bleed-out over 60 minutes, followed by chronic resuscitation of 0, 5, or 10 mL/kg/hr RL for 20 hours. Hepatocellular function was determined by an in vivo indocyanine green clearance technique. Hepatic microvascular blood flow was assessed by laser Doppler flowmetry. Plasma levels of interleukin-6 (IL-6) were determined by bioassay. Chronic resuscitation with 5 mL/kg/hr RL, but not with 0 or 10 mL/kg/hr RL, restored cardiac output, hepatocellular function, and hepatic microvascular blood flow at 20 hours after hemorrhage. The regimen above also reduced plasma IL-6 levels. Because chronic resuscitation with 5 mL/kg/hr RL after trauma-hemorrhage and acute fluid replacement restored hepatocellular function and hepatic microvascular blood flow and decreased plasma levels of IL-6, we propose that chronic fluid resuscitation in addition to acute fluid replacement should be routinely used in experimental studies of trauma-hemorrhage.

Orthotopic Transplantation of Achilles Tendon Allograft in Rats

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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

Are There Deleterious Cardiac Effects of Acute and Chronic Endurance Exercise?

Science.gov (United States)

Eijsvogels, Thijs M. H.; Fernandez, Antonio B.; Thompson, Paul D.

2015-01-01

Multiple epidemiological studies document that habitual physical activity reduces the risk of atherosclerotic cardiovascular disease (ASCVD), and most demonstrate progressively lower rates of ASCVD with progressively more physical activity. Few studies have included individuals performing high-intensity, lifelong endurance exercise, however, and recent reports suggest that prodigious amounts of exercise may increase markers for, and even the incidence of, cardiovascular disease. This review examines the evidence that extremes of endurance exercise may increase cardiovascular disease risk by reviewing the causes and incidence of exercise-related cardiac events, and the acute effects of exercise on cardiovascular function, the effect of exercise on cardiac biomarkers, including “myocardial” creatine kinase, cardiac troponins, and cardiac natriuretic peptides. This review also examines the effect of exercise on coronary atherosclerosis and calcification, the frequency of atrial fibrillation in aging athletes, and the possibility that exercise may be deleterious in individuals genetically predisposed to such cardiac abnormalities as long QT syndrome, right ventricular cardiomyopathy, and hypertrophic cardiomyopathy. This review is to our knowledge unique because it addresses all known potentially adverse cardiovascular effects of endurance exercise. The best evidence remains that physical activity and exercise training benefit the population, but it is possible that prolonged exercise and exercise training can adversely affect cardiac function in some individuals. This hypothesis warrants further examination. PMID:26607287

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.

Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats.

Science.gov (United States)

Luo, Wenqi; Jia, Yixin; Zheng, Shuai; Li, Yan; Han, Jie; Meng, Xu

2017-01-01

Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential ( AP ) and the transient outward potassium current ( I to ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4 th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and I to current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2 nd day and moderate rejection at the 4 th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration ( APD ) of cardiomyocytes in the allogeneic group was significantly prolonged ( APD 90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2 nd day, P=0.0016; APD 90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4 th day, P=0.0064). The current density of I to was significantly decreased at the 4 th day after cardiac transplantation. The APD of

Successful treatment of 54 patients with acute renal failure after cardiac surgery

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Lei CHEN

2015-06-01

Full Text Available Objectives　To evaluate the result of treatment of acute renal failure (ARF in patients after cardiac surgery. Methods　The clinical data of 54 cases admitted to the hospital from Jan. 2004 to Jan. 2014 and suffered from ARF after cardiac surgery were retrospectively analyzed. Among 54 cases, there were 35 males and 19 females, aged from one month to 79 years with a median of 52 years. The surgical procedures included coronary artery bypass grafting (CABG, 10 cases, valve surgery (22 cases, combined CABG and valve surgery (4 cases, operation on aorta (14 case, and radical correction of Fallot tetralogy (4 cases. After the operations mentioned above, 50 patients received continuous renal replacement therapy (CRRT, and 4 patients received peritoneal dialysis. Results　Nine patients died, the mortality rate was 16.7%. Exploratory hemostasis by thoracotomy was performed in 8 patients, and extubation failure occurred in 4 cases. Of the 9 non-survivors, 6 died from multiple organ failure (MOF, 2 died from cerebral hemorrhage, and one died from acute respiratory failure. Serum creatinine (SCr and blood urea nitrogen (BUN levels declined obviously after CRRT and peritoneal dialysis (P<0.05, and all the patients were shown to have stable hemodynamics in the course of treatment, and no hemorrhage or embolism occurred. Conclusions　ARF after cardiac surgery should be detected early and treated in time. CRRT and peritoneal dialysis are safe, convenient and effective procedures, and may decrease the mortality rate in patients with ARF after cardiac surgery. DOI: 10.11855/j.issn.0557-7402.2015.04.13

Adefovir nephrotoxicity in a renal allograft recipient

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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.

An unexpected complication of acute pancreatitis: Intra-cardiac thrombus.

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Keskin, Muhammed; Gümüşdağ, Ayça; Börklü, Edibe Betül; Dayı, Şennur Ünal; Avcı, İlhan İlker; Güvenç, Tolga Sinan; Güngör, Barış; Karabay, Can Yücel; Kozan, Ömer

2017-05-01

Left atrial thrombus after acute pancreatitis (AP) is a rare clinical statement. Because of induction of systemic prothrombotic process by AP; some patients with underlying risk factors may develop an intra-cardiac thrombus. We present a 53years-old-woman with moderate mitral stenosis and atrial fibrillation. However the patient was under warfarin treatment, she developed a big left atrial big thrombus which was originated from left atrial appendage after she was suffered from AP. Copyright © 2016 Elsevier Inc. All rights reserved.

Concentration of In-111-oxine-labeled autologous leukocytes in noninfected and nonrejecting renal allografts: concise communication

International Nuclear Information System (INIS)

Collier, B.D.; Isitman, A.T.; Kaufman, H.M.; Rao, S.A.; Knobel, J.; Hellman, R.S.; Zielonka, J.S.; Pelc, L.

1984-01-01

Autologous leukocytes labeled with In-111 oxine (ILL) concentrated in the renal allografts of eight patients for whom transplant rejection, infection, or acute tubular necrosis (ATN) could be excluded. All patients had good-to-adequate renal function at the time of ILL scintigraphy, and none developed rejection or renal transplant failure during a 1-mo follow-up period. It is concluded that normally functioning renal allografts without evidence of rejection, infection, or ATN often will concentrate ILL. When a baseline study is not available for comparison, this phenomenon limits the value of ILL scintigraphy as a diagnostic test for transplant rejection or infection

Acute effects of sex steroid hormones on susceptibility to cardiac arrhythmias: a simulation study.

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Pei-Chi Yang

2010-01-01

Full Text Available Acute effects of sex steroid hormones likely contribute to the observation that post-pubescent males have shorter QT intervals than females. However, the specific role for hormones in modulating cardiac electrophysiological parameters and arrhythmia vulnerability is unclear. Here we use a computational modeling approach to incorporate experimentally measured effects of physiological concentrations of testosterone, estrogen and progesterone on cardiac ion channel targets. We then study the hormone effects on ventricular cell and tissue dynamics comprised of Faber-Rudy computational models. The "female" model predicts changes in action potential duration (APD at different stages of the menstrual cycle that are consistent with clinically observed QT interval fluctuations. The "male" model predicts shortening of APD and QT interval at physiological testosterone concentrations. The model suggests increased susceptibility to drug-induced arrhythmia when estradiol levels are high, while testosterone and progesterone are apparently protective. Simulations predict the effects of sex steroid hormones on clinically observed QT intervals and reveal mechanisms of estrogen-mediated susceptibility to prolongation of QT interval. The simulations also indicate that acute effects of estrogen are not alone sufficient to cause arrhythmia triggers and explain the increased risk of females to Torsades de Pointes. Our results suggest that acute effects of sex steroid hormones on cardiac ion channels are sufficient to account for some aspects of gender specific susceptibility to long-QT linked arrhythmias.

Radioimmunoassay of human cardiac tropomyosin in acute myocardial infarction

Energy Technology Data Exchange (ETDEWEB)

Cummins, P; McGurk, B; Littler, W A [Queen Elizabeth Hospital, Birmingham (UK)

1981-03-01

Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac /sup 125/I-labelled tropomyosin in human sera down to levels of 1 ng/ml. Values for human cardiac tropomyosin in normal patients ranged from less than 1 to 3 ng/ml. In 18 patients with acute myocardial infarction all had elevated tropomyosin levels ranging from 41 to above 200 ng/ml with a mean peak level of 101 ng/ml. In this study there were no false positive or false negative results. In the initial stages of infarction the time course of appearance and peak levels of cardiac tropomyosin, total creatine kinase and creatine kinase MB isoenzyme were similar. Although total creatine kinase and creatine kinase MB isoenzyme levels were normal after 72 h in patients with single, uncomplicated infarction, cardiac tropomyosin levels were still significantly elevated above normal after this time, being 30-60% of peak valuctional hourly rate of absorption and the plasma /sup 32/P radioactivity at 60 min corrected for extracellular fluid volume provided the best app elements, the characteristics of which are determined by employing the Lagrange multiplier concept. Unknowns of the resulting simultaneous equation consist of usual nodal displacements of the whole stru element codes. Therefore, FAST should be useful in several areas for which all other codes are too unwieldy and expensivnt makers was established, in which the investigations and studies have started.

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

Coronary ostial involvement in acute aortic dissection: detection with 64-slice cardiac CT.

LENUS (Irish Health Repository)

Ryan, E Ronan

2012-02-01

A 41-year-old man collapsed after lifting weights at a gym. Following admission to the emergency department, a 64-slice cardiac computed tomography (CT) revealed a Stanford Type A aortic dissection arising from a previous coarctation repair. Multiphasic reconstructions demonstrated an unstable, highly mobile aortic dissection flap that extended proximally to involve the right coronary artery ostium. Our case is an example of the application of electrocardiogram-gated cardiac CT in directly visualizing involvement of the coronary ostia in acute aortic dissection, which may influence surgical management.

Cardiac function in acute hypothyroidism

International Nuclear Information System (INIS)

Donaghue, K.; Hales, I.; Allwright, S.; Cooper, R.; Edwards, A.; Grant, S.; Morrow, A.; Wilmshurst, E.; Royal North Shore Hospital, Sydney

1985-01-01

It has been established that chronic hypothyroidism may affect cardiac function by several mechanisms. It is not known how long the patient has to be hypothyroid for cardiac involvement to develop. This study was undertaken to assess the effect of a short period of hypothyroidism (10 days) on cardiac function. Nine patients who had had total tyroidectomy, had received ablative radioiodine for thyroid cancer and were euthyroid on replacement therapy were studied while both euthyroid and hypothyroid. Cardiac assessment was performed by X-ray, ECG, echocardiography and gated blood-pool scans. After 10 days of hypothyroidisms, the left-ventricular ejection fraction failed to rise after exercise in 4 of the 9 patients studied, which was significant (P<0.002). No significant changes in cardiac size or function at rest were detected. This functional abnormality in the absence of any demonstrable change in cardiac size and the absence of pericardial effussion with normal basal function suggest that short periods of hypothyroidism may reduce cardiac reserve, mostly because of alterations in metabolic function. (orig.)

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

Evaluation of cardiac injury biomarkers in cattle with acute clinical mastitis

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meysam fllah

2016-05-01

   This study was carried out on 30 Holstein dairy cattle with acute clinical mastitis (ACM and 30 healthy ones. After confirmation of ACM through clinical examination, venous blood samples were collected and cardiac troponin I (cTnI was measured using chemiluminescence assay. Cardiac enzymes activities including CK-MB, AST and LDH were analyzed with special kits and spectrophotometric method. According to the findings mean heart rate (p=0.001, respiratory rate (p=0.026, and rectal temperature (p=0.030 were significantly increased in diseased group. cTnI level was 1.018 ± 0.235 ng/ml in cattle with ACM, which was significantly higher than healthy cattle (0.011±0.006 ng/ml; p=0.000. Other cardiac biomarkers were increased in diseased group, however elevation of serum activities of AST (p=0.047 and CK-MB (p=0.000 were statically significant. Although serum LDH activity in diseased group was higher than control group; but this difference was statistically non-significant (p=0.454. There were significant positive correlations between cTnI concentration with heart rate (p=0.018; r=0.853, respiratory rate (p=0.024; r=0.671, and rectal temperature (p=0.038; r=0.542. Heart rates were significantly correlated with serum activities of CK-MB (p=0.047; r=0.722 and AST (p=0.035; r=0.649. These results indicate some degree of heart damage caused by acute clinical mastitis in dairy cattle.

Pharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.

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Mégarbane, Bruno; Aslani, Arsia Amir; Deye, Nicolas; Baud, Frédéric J

2008-05-01

Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. To review the utility and limits of PK/PD studies of cardiac toxicity. Discussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings. A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

IFN-γ-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection: Paradoxical post-transplantation effects of IFN-γ.

Science.gov (United States)

Xu, Xiaoguang; Huang, Haiyan; Wang, Qiang; Cai, Ming; Qian, Yeyong; Han, Yong; Wang, Xinying; Gao, Yu; Yuan, Ming; Xu, Liang; Yao, Chen; Xiao, Li; Shi, Bingyi

2017-02-01

IFN-γ is a protypical proinflammatory cytokine that plays a central role in inflammation and acute graft rejection. Accumulating evidence indicates that IFN-γ can exert previously unexpected immunoregulatory activities. However, little is known about the role of IFN-γ secreted by Th1-like regulatory T cells in human kidney transplantation. To determine the function of IFN-γ in acute T cell-mediated renal allograft rejection (ACR), we examined serum cytokine expression profiles in ACR patients by human cytokine multiplex immunoassay and analyzed the cellular origins of IFN-γ in peripheral blood and renal allograft biopsies from ACR cases and controls by flow cytometry and immunohistochemistry, respectively. The results showed significant reduction in serum concentrations of Th1-inducing cytokines IL-12p70 and IFN-γ as well as Th2-related cytokine IL-4 in ACR patients compared with stable controls. However, levels of several Th1-, Th2- and Th17-related cytokines, such as IL-2, TNF-α, TNF-β, IL-12 (p40), IL-10, IL-15, IL-17, IL-21, and IL-23, as well as the frequencies of Th1 and Th17 cell, did not differ between ACR cases and stable controls. Moreover, we found the levels of IFN-γ were correlated with those of the anti-inflammatory factor, IL-1 receptor antagonist (IL-1Ra) in ACR. Notably, the Th1-like Treg cell-to-Foxp3 - Th1 cell ratio was significantly lower in ACR patients compared with that in stable controls. In graft biopsies from ACR patients, Treg cells and Th1-like Treg cells were less abundant than those without ACR. Our study indicates that IFN-γ secreted from Th1-like Treg cells negatively modulates ACR. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

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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

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

Use of echocardiography at diagnosis and detection of acute cardiac disease in youth with systemic lupus erythematosus.

Science.gov (United States)

Chang, J C; Knight, A M; Xiao, R; Mercer-Rosa, L M; Weiss, P F

2018-01-01

Objectives There are no guidelines on the use of echocardiography to detect cardiac manifestations of childhood-onset systemic lupus erythematosus (SLE). We quantify the prevalence of acute cardiac disease in youth with SLE, describe echocardiogram utilization at SLE diagnosis, and compare regional echocardiogram use with incident cardiac diagnoses. Methods Using the Clinformatics® DataMart (OptumInsight, Eden Prairie, MN) de-identified United States administrative database from 2000 to 2013, we identified youth ages 5-24 years with new-onset SLE (≥3 ICD-9 SLE codes 710.0, > 30 days apart) and determined the prevalence of diagnostic codes for pericardial disease, myocarditis, endocarditis, and valvular insufficiency. Multiple logistic regression was used to identify factors associated with echocardiography during the baseline period, up to one year before or six months after SLE diagnosis. We calculated a regional echocardiogram utilization index, which is the ratio of observed use over the mean predicted probability based on all available baseline characteristics. Spearman's rank correlation coefficient was used to evaluate the association between regional echocardiogram utilization indices and percentage of imaged youth diagnosed with their first cardiac manifestation following echocardiography. Results Among 699 youth with new-onset SLE, 18% had ≥ 1 diagnosis code for acute cardiac disease, of which valvular insufficiency and pericarditis were most common. Twenty-five percent of all youth underwent echocardiogram during the baseline period. Regional echocardiogram use was positively correlated with the percentage of imaged youth found to have cardiac disease (ρ = 0.71, p = 0.05). There was up to a five-fold difference in adjusted odds of baseline echocardiography between low- and high-utilizing regions (OR = 0.19, p = 0.007). Conclusion Nearly one-fifth of youth with new-onset SLE have acute cardiac manifestations; however, use of

Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

Science.gov (United States)

Moreira-Gonçalves, Daniel; Henriques-Coelho, Tiago; Fonseca, Hélder; Ferreira, Rita; Padrão, Ana Isabel; Santa, Cátia; Vieira, Sara; Silva, Ana Filipa; Amado, Francisco; Leite-Moreira, Adelino; Duarte, José Alberto

2015-09-01

The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and

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.

Thioredoxin priming prolongs lung allograft survival by promoting immune tolerance.

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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

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

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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.

Acute kidney injury in septua- and octogenarians after cardiac surgery

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Schmid Christof

2011-08-01

Full Text Available Abstract Background An increasing number of septua- and octogenarians undergo cardiac surgery. Acute kidney injury (AKI still is a frequent complication after surgery. We examined the incidence of AKI and its impact on 30-day mortality. Methods A retrospective study between 01/2006 and 08/2009 with 299 octogenarians, who were matched for gender and surgical procedure to 299 septuagenarians at a university hospital. Primary endpoint was AKI after surgery as proposed by the RIFLE definition (Risk, Injury, Failure, Loss, End-stage kidney disease. Secondary endpoint was 30-day mortality. Perioperative mortality was predicted with the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE. Results Octogenarians significantly had a mean higher logistic EuroSCORE compared to septuagenarians (13.2% versus 8.5%; p -1 × 1.73 m-2. In contrast, septuagenarians showed a slightly higher median body mass index (28 kg × m-2 versus 26 kg × m-2 and were more frequently active smoker at time of surgery (6.4% versus 1.6%, p The RIFLE classification provided accurate risk assessment for 30-day mortality and fair discriminatory power. Conclusions The RIFLE criteria allow identifying patients with AKI after cardiac surgery. The high incidence of AKI in septua- and octogenarians after cardiac surgery should prompt the use of RIFLE criteria to identify patients at risk and should stimulate institutional measures that target AKI as a quality improvement initiative for patients at advanced age.

Acute hypopituitarism associated with periorbital swelling and cardiac dysfunction in a patient with pituitary tumor apoplexy: a case report.

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Ohara, Nobumasa; Yoneoka, Yuichiro; Seki, Yasuhiro; Akiyama, Katsuhiko; Arita, Masataka; Ohashi, Kazumasa; Suzuki, Kazuo; Takada, Toshinori

2017-08-24

Pituitary tumor apoplexy is a rare clinical syndrome caused by acute hemorrhage or infarction in a preexisting pituitary adenoma. It typically manifests as an acute episode of headache, visual disturbance, mental status changes, cranial nerve palsy, and endocrine pituitary dysfunction. However, not all patients present with classical symptoms, so it is pertinent to appreciate the clinical spectrum of pituitary tumor apoplexy presentation. We report an unusual case of a patient with pituitary tumor apoplexy who presented with periorbital edema associated with hypopituitarism. An 83-year-old Japanese man developed acute anterior hypopituitarism; he showed anorexia, fatigue, lethargy, severe bilateral periorbital edema, and mild cardiac dysfunction in the absence of headache, visual disturbance, altered mental status, and cranial nerve palsy. Magnetic resonance imaging showed a 2.5-cm pituitary tumor containing a mixed pattern of solid and liquid components indicating pituitary tumor apoplexy due to hemorrhage in a preexisting pituitary adenoma. Replacement therapy with oral hydrocortisone and levothyroxine relieved his symptoms of central adrenal insufficiency, central hypothyroidism, periorbital edema, and cardiac dysfunction. Common causes of periorbital edema include infections, inflammation, trauma, allergy, kidney or cardiac dysfunction, and endocrine disorders such as primary hypothyroidism. In the present case, the patient's acute central hypothyroidism was probably involved in the development of both periorbital edema and cardiac dysfunction. The present case highlights the need for physicians to consider periorbital edema as an unusual predominant manifestation of pituitary tumor apoplexy.

Absence of acute skeletal and cardiac muscle injuries in amateur triathletes

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Luiz Carlos C. Jovita

2009-01-01

Full Text Available Creatine kinase (CK and creatine kinase muscle-brain fraction (CK-MB might be associated with damage to muscle and cardiac tissue, respectively, as a consequence of intense prolonged exercise. The objective of the present study was to determine whether acute changes in CK and CK-MB reflect some risk of damage to skeletal and cardiac muscles in amateur athletes after Ironman 70.3. The sample consisted of 10 male athlete volunteers (age: 34.0 ± 9.2 years. A venous blood sample (2 mL was collected before and after the competition. The volunteers completed the race in 5h20min to 6 h. CK and CK-MB were analyzed by an enzymatic method using Wiener labreagent in an automatic spectrophotometer (Targa bt 3000. The nonparametric Wilcoxon test showed significant differences (p < .05 in the variables studied before and after the competition. Mean CK was 112.23 ± 34.9 and 458.0 ± 204.9 U/L (Δ% = 418.2, and mean CK-MB was 7.4 ± 2.6 and 10.8 ± 3.9 U/L (Δ% = 153.3 before and after the event, respectively. The relative variation in CK-MB compared to CK before (6.9% and after (2.5% the competition showed that the former is not a factor of concern during intense prolonged exercise such as Ironman 70.3. In conclusion, the acute increase in CK after the end of intense prolonged exercise indicates skeletal muscle damage which, however, is considered to be normal for athletes. With respect to CK-MB, cardiac muscle injury was inexistent.

Complications of massive allograft reconstruction for bone tumors

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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

Investigation of association between donors' and recipients' NADPH oxidase p22(phox) C242T polymorphism and acute rejection, delayed graft function and blood pressure in renal allograft recipients.

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Mandegary, Ali; Rahmanian-Koshkaki, Sara; Mohammadifar, Mohammad-Amir; Pourgholi, Leila; Mehdipour, Mohammad; Etminan, Abbas; Ebadzadeh, Mohammad-Reza; Fazeli, Faramarz; Azmandian, Jalal

2015-01-01

Production of reactive oxygen species (ROS) and thereby induction of oxidative stress seem to be one of the major mediators of inflammatory adverse outcomes after renal transplantation. p22(phox) is a polymorphic subunit of NAD(P)H-oxidase that is critical for activation and stabilization of the enzyme. This enzyme is involved in the production of superoxide that triggers inflammatory injuries to the kidney. So in this study, the association between donors and recipients' C242T polymorphism of p22(phox) and acute rejection (AR), delayed graft function (DGF), creatinine clearance (CrCl), and blood pressure in renal-allograft recipients was studied. One hundred ninety six donor-recipient pairs were studied. The C242T polymorphism of p22(phox) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to p22 genotype, the subjects were divided in wild-type (CC) and T allele carriers (CT+TT). Transplantation outcomes were determined using acute rejection and delayed graft function criteria. The mean arterial pressure was also measured monthly after transplantation. There was a significant association between the recipients' p22(phox) polymorphism and DGF occurrence (OR=2.5, CI: 1.2-4.9, p=0.0009). No significant association was detected between donors' p22(phox) polymorphism and AR and DGF events. CrCl during the six months follow-up after transplantation was lower in the patients who received allograft from donors carrying 242T allele (B=-12.8, CI: -22.9-12.8 (-22.9 to -2.6)). Changes in the blood pressure were not different among the patients having different genotypes of p22(phox). These results suggest that the recipients' p22(phox) C242T polymorphism may be a major risk factor for DGF in renal transplantation. Moreover, the donors' 242T allele seems to affect the rate of CrCl in the renal allograft recipients. Copyright © 2014. Published by Elsevier B.V.

Allograft materials in phalloplasty: a comparative analysis.

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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

Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

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Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

2016-01-01

Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

Magnetic resonance imaging of massive bone allografts with histologic correlation

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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)

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

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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

Irradiated strut allografts for reconstructing tumour defects: how effective?

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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)

Risk of Acute Kidney Injury in Patients Randomized to a Restrictive Versus Liberal Approach to Red Blood Cell Transfusion in Cardiac Surgery: A Substudy Protocol of the Transfusion Requirements in Cardiac Surgery III Noninferiority Trial.

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Garg, Amit X; Shehata, Nadine; McGuinness, Shay; Whitlock, Richard; Fergusson, Dean; Wald, Ron; Parikh, Chirag; Bagshaw, Sean M; Khanykin, Boris; Gregory, Alex; Syed, Summer; Hare, Gregory M T; Cuerden, Meaghan S; Thorpe, Kevin E; Hall, Judith; Verma, Subodh; Roshanov, Pavel S; Sontrop, Jessica M; Mazer, C David

2018-01-01

When safe to do so, avoiding blood transfusions in cardiac surgery can avoid the risk of transfusion-related infections and other complications while protecting a scarce resource and reducing costs. This protocol describes a kidney substudy of the Transfusion Requirements in Cardiac Surgery III (TRICS-III) trial, a multinational noninferiority randomized controlled trial to determine whether the risk of major clinical outcomes in patients undergoing planned cardiac surgery with cardiopulmonary bypass is no greater with a restrictive versus liberal approach to red blood cell transfusion. The objective of this substudy is to determine whether the risk of acute kidney injury is no greater with a restrictive versus liberal approach to red blood cell transfusion, and whether this holds true in patients with and without preexisting chronic kidney disease. Multinational noninferiority randomized controlled trial conducted in 73 centers in 19 countries (2014-2017). Patients (~4800) undergoing planned cardiac surgery with cardiopulmonary bypass. The primary outcome of this substudy is perioperative acute kidney injury, defined as an acute rise in serum creatinine from the preoperative value (obtained in the 30-day period before surgery), where an acute rise is defined as ≥26.5 μmol/L in the first 48 hours after surgery or ≥50% in the first 7 days after surgery. We will report the absolute risk difference in acute kidney injury and the 95% confidence interval. We will repeat the primary analysis using alternative definitions of acute kidney injury, including staging definitions, and will examine effect modification by preexisting chronic kidney disease (defined as a preoperative estimated glomerular filtration rate [eGFR] blood cell transfusion in the presence of anemia during cardiac surgery done with cardiopulmonary bypass. www.clinicaltrials.gov; clinical trial registration number NCT 02042898.

Role of cardiac volume receptors in the control of ADH release during acute simulated weightlessness in man

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Convertino, V. A.; Benjamin, B. A.; Keil, L. C.; Sandler, H.

1984-01-01

Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes, designed to induce central blood volume shifts in ten cardiac and one heart-lung transplant recipients, to assess the contribution of cardiac volume receptors in the control of ADH release during the initial acute phase of exposure to weightlessness. Each subject underwent 15 min of a sitting-control period (C) followed by 30 min of 6 deg headdown tilt (T) and 30 min of resumed sitting (S). Venous blood samples and cardiac dimensions were taken at 0 and 15 min of C; 5, 15, and 30 min of T; and 5, 15, and 30 min of S. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Heart rate and blood pressure were recorded every two min. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 ml in C to 106 ml in T and returned to 87 ml in S. Plasma ADH was reduced by 20 percent (P less than 0.05) with T, and returned to control levels with S. These responses were similar in six normal cardiac-innervated control subjects. These data may suggest that cardiac volume receptors are not the primary mechanism for the control of ADH release during acute central volume shifts in man.

Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection.

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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.

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

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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

Diagnostic Accuracy of a New Cardiac Electrical Biomarker for Detection of Electrocardiogram Changes Suggestive of Acute Myocardial Ischemic Injury

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Schreck, David M; Fishberg, Robert D

2014-01-01

Objective A new cardiac “electrical” biomarker (CEB) for detection of 12-lead electrocardiogram (ECG) changes indicative of acute myocardial ischemic injury has been identified. Objective was to test CEB diagnostic accuracy. Methods This is a blinded, observational retrospective case-control, noninferiority study. A total of 508 ECGs obtained from archived digital databases were interpreted by cardiologist and emergency physician (EP) blinded reference standards for presence of acute myocardial ischemic injury. CEB was constructed from three ECG cardiac monitoring leads using nonlinear modeling. Comparative active controls included ST voltage changes (J-point, ST area under curve) and a computerized ECG interpretive algorithm (ECGI). Training set of 141 ECGs identified CEB cutoffs by receiver-operating-characteristic (ROC) analysis. Test set of 367 ECGs was analyzed for validation. Poor-quality ECGs were excluded. Sensitivity, specificity, and negative and positive predictive values were calculated with 95% confidence intervals. Adjudication was performed by consensus. Results CEB demonstrated noninferiority to all active controls by hypothesis testing. CEB adjudication demonstrated 85.3–94.4% sensitivity, 92.5–93.0% specificity, 93.8–98.6% negative predictive value, and 74.6–83.5% positive predictive value. CEB was superior against all active controls in EP analysis, and against ST area under curve and ECGI by cardiologist. Conclusion CEB detects acute myocardial ischemic injury with high diagnostic accuracy. CEB is instantly constructed from three ECG leads on the cardiac monitor and displayed instantly allowing immediate cost-effective identification of patients with acute ischemic injury during cardiac rhythm monitoring. PMID:24118724

Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

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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

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

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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

Two-stage, in silico deconvolution of the lymphocyte compartment of the peripheral whole blood transcriptome in the context of acute kidney allograft rejection.

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Shannon, Casey P; Balshaw, Robert; Ng, Raymond T; Wilson-McManus, Janet E; Keown, Paul; McMaster, Robert; McManus, Bruce M; Landsberg, David; Isbel, Nicole M; Knoll, Greg; Tebbutt, Scott J

2014-01-01

Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of these differentially

Two-stage, in silico deconvolution of the lymphocyte compartment of the peripheral whole blood transcriptome in the context of acute kidney allograft rejection.

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Casey P Shannon

Full Text Available Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of

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

Application of radiation sterilization to bone allografts

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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)

Laparoscopic cholecystectomy in a cardiac transplant recipient.

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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.

Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation.

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Matsumura, Y; Marchevsky, A; Zuo, X J; Kass, R M; Matloff, J M; Jordan, S C

1995-06-15

Lung transplantation is now routinely performed for a wide range of end-stage cardiopulmonary disorders. Despite overcoming the problems associated with early acute rejection, chronic rejection (CR) in the form of obliterative bronchiolitis has emerged as the primary cause of late graft loss. The mechanisms involved in the development of CR of lung allografts are poorly understood, and no effective therapy is currently available. To better understand the pathological events associated with CR and tolerance, we examined two models of lung allograft rejection established in our laboratory. First, we exchanged left lung allografts between moderately histoincompatible inbred rat strains (WKY-->F344: n = 42 and F344-->WKY: n = 40). The WKY-->F344 model was previously shown to develop spontaneous tolerance, while the converse model (F344-->WKY) showed persistent acute rejection. The purpose of this investigation was to assess histopathological changes associated with long-term grafts left in place up to 140 days after transplant. To confirm that tolerance had developed, skin-grafting experiments were performed. Five skin grafts from each strain were placed on lung allograft recipients on day 35 after transplant and skin allograft survival was assessed and compared with controls. Acute rejection (AR) was graded histologically (stage O-IV) and the pathologic intensity of inflammation and CR were graded (0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = 76-100%) on percentage of involvement with the following categories being examined: (a) lymphocytic infiltration (perivascular, peribronchial, and peribronchiolar) and (b) vasculitis, edema, hemorrhage, and necrosis. Finally, chronic rejection was diagnosed by the presence of intimal hyperplasia, interstitial fibrosis, peribronchiolar fibrosis, bronchiolitis obliterans, and bronchiectasis. The WKY-->F344 animals showed progressive AR (stage III, day 21). Thereafter, the AR subsided spontaneously and was stage 0 on day

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.

Acute cardiac events and deployment of emergency medical teams and automated external defibrillators in large football stadiums in the Netherlands.

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van de Sandt, Femke; Umans, Victor

2009-10-01

The incidence of acute cardiac events - including out-of-hospital cardiac arrest - may be increased in visitors of large sports stadiums when compared with the general population. This study sought to investigate the incidence of acute cardiac events inside large Dutch football stadiums, as well as the emergency response systems deployed in these stadiums and the success rate for in-stadium resuscitation. Retrospective cohort study using a questionnaire sent to the 20 Dutch stadiums that hosted professional matches during the 2006-2007 and 2007-2008 football seasons. Stadium capacity ranged from 3600 to 51 600 spectators. Nearly 13 million spectators attended 686 'Eredivisie' (Honorary Division) and European football matches. All stadiums distribute multiple emergency medical teams among the spectators. Eighty-five percent of the stadiums have an ambulance standby during matches, 95% of the stadiums were equipped with automated external defibrillators (AEDs) during the study period. On an average, one AED was available for every 7576 spectators (range 1800-29 600). Ninety-three cardiac events were reported (7.3 per 1 million spectators). An AED was used 22 times (1.7 per 1 million spectators). Resuscitation was successful in 18 cases (82%, 95% confidence interval: 61-93). The incidence of out-of-hospital cardiac arrest inside large football stadiums in the Netherlands, albeit increased when compared with the general population, is low. The success rate for in-stadium resuscitation by medical teams equipped with AEDs is high. Dutch stadiums appear vigilant in regard to acute cardiac events. This report highlights the importance of adequate emergency medical response systems (including AEDs) in large sports venues.

In vivo effects of high-dose steroids on nucleic acid content of immunocompetent cells of renal allograft recipients

International Nuclear Information System (INIS)

Walle, A.J.; Wong, G.Y.; Suthanthiran, M.; Rubin, A.L.; Stenzel, K.H.

1988-01-01

High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and of proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of 3 H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo

Musculoskeletal allograft risks and recalls in the United States.

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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.

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

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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.

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

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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.

Surgical techniques and radiological findings of meniscus allograft transplantation.

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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.

Risk of Acute Kidney Injury in Patients Randomized to a Restrictive Versus Liberal Approach to Red Blood Cell Transfusion in Cardiac Surgery: A Substudy Protocol of the Transfusion Requirements in Cardiac Surgery III Noninferiority Trial

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Amit X. Garg

2018-01-01

Full Text Available Background: When safe to do so, avoiding blood transfusions in cardiac surgery can avoid the risk of transfusion-related infections and other complications while protecting a scarce resource and reducing costs. This protocol describes a kidney substudy of the Transfusion Requirements in Cardiac Surgery III (TRICS-III trial, a multinational noninferiority randomized controlled trial to determine whether the risk of major clinical outcomes in patients undergoing planned cardiac surgery with cardiopulmonary bypass is no greater with a restrictive versus liberal approach to red blood cell transfusion. Objective: The objective of this substudy is to determine whether the risk of acute kidney injury is no greater with a restrictive versus liberal approach to red blood cell transfusion, and whether this holds true in patients with and without preexisting chronic kidney disease. Design and Setting: Multinational noninferiority randomized controlled trial conducted in 73 centers in 19 countries (2014-2017. Patients: Patients (~4800 undergoing planned cardiac surgery with cardiopulmonary bypass. Measurements: The primary outcome of this substudy is perioperative acute kidney injury, defined as an acute rise in serum creatinine from the preoperative value (obtained in the 30-day period before surgery, where an acute rise is defined as ≥26.5 μmol/L in the first 48 hours after surgery or ≥50% in the first 7 days after surgery. Methods: We will report the absolute risk difference in acute kidney injury and the 95% confidence interval. We will repeat the primary analysis using alternative definitions of acute kidney injury, including staging definitions, and will examine effect modification by preexisting chronic kidney disease (defined as a preoperative estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m 2 . Limitations: It is not possible to blind patients or providers to the intervention; however, objective measures will be used to assess

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

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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.

Early rise in postoperative creatinine for identification of acute kidney injury after cardiac surgery.

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Karkouti, Keyvan; Rao, Vivek; Chan, Christopher T; Wijeysundera, Duminda N

2017-08-01

Acute kidney injury (AKI) is a potentially serious complication of cardiac surgery. Treatment strategies are unlikely to prove efficacious unless patients are identified and treated soon after the onset of injury. In this observational study, we determined and validated the ability of an early rise in postoperative serum creatinine to identify patients who suffer AKI during cardiac surgery. The relationship between an early rise in creatinine (immediate postoperative / preoperative creatinine) and AKI (> 50% increase in creatinine by postoperative calendar days 1or 2) was determined by logistic regression modelling. Existing databases were used for model development (n = 4,820; one institution) and validation (n = 6,553; 12 institutions). Acute kidney injury occurred in 9.1% (n = 437) and 9.8% (n = 645) of patients in the development and validation sets, respectively. An early rise in creatinine was related to AKI (P 1.30 (n = 127), the sensitivity, specificity, positive, and negative predictive values for AKI in the development set were 20% (95% CI, 16 to 24), 99% (95% CI, 99 to 99), 68% (95% CI, 59 to 76), and 93% (95% CI, 92 to 93), respectively. In patients undergoing cardiac surgery with cardiopulmonary bypass, an early rise in postoperative creatinine is a useful marker for the early identification of AKI patients. This could allow inclusion of such patients in clinical trials of promising therapeutic strategies that need to be initiated soon after the onset of injury.

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

High-sensitivity cardiac troponin I and risk of heart failure in patients with suspected acute coronary syndrome: a cohort study.

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Stelzle, Dominik; Shah, Anoop S V; Anand, Atul; Strachan, Fiona E; Chapman, Andrew R; Denvir, Martin A; Mills, Nicholas L; McAllister, David A

2018-01-01

Heart failure may occur following acute myocardial infarction, but with the use of high-sensitivity cardiac troponin assays we increasingly diagnose patients with minor myocardial injury. Whether troponin concentrations remain a useful predictor of heart failure in patients with acute coronary syndrome is uncertain. We identified all consecutive patients (n = 4748) with suspected acute coronary syndrome (61 ± 16 years, 57% male) presenting to three secondary and tertiary care hospitals. Cox-regression models were used to evaluate the association between high-sensitivity cardiac troponin I concentration and subsequent heart failure hospitalization. C-statistics were estimated to evaluate the predictive value of troponin for heart failure hospitalization. Over 2071 years of follow-up there were 83 heart failure hospitalizations. Patients with troponin concentrations above the upper reference limit (URL) were more likely to be hospitalized with heart failure than patients below the URL (118/1000 vs. 17/1000 person years, adjusted hazard ratio: 7.0). Among patients with troponin concentrations acute coronary syndrome. The strongest associations were observed in patients with troponin concentrations in the normal reference range, in whom high-sensitivity cardiac troponin assays identify those at increased risk of heart failure who may benefit from further investigation and treatment. © The Author 2017. Published on behalf of the European Society of Cardiology

Moringa oleifera extract (Lam) attenuates Aluminium phosphide-induced acute cardiac toxicity in rats.

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Gouda, Ahmed S; El-Nabarawy, Nagla A; Ibrahim, Samah F

2018-01-01

Moringa oleifera extract (Lam) has many antioxidant and protective properties. Objective: to investigate the antioxidant activities of Lam in counteracting the high oxidative stress caused by acute sub-lethal aluminium phosphide (AlP) intoxication in rat heart. These activities will be detected by histopathological examination and some oxidative stress biomarkers. a single sub-lethal dose of Alp (2 mg/kg body weight) was administered orally, and Lam was given orally at a dose (100 mg/kg body weight) one hour after receiving AlP to rats. aluminium phosphide caused significant cardiac histopathological changes with a significant increase in malondialdehyde (MDA); lipid peroxidation marker; and a significant depletion of antioxidant enzymes (catalase and glutathione reductase). However, treatment with Lam protected efficiently the cardiac tissue of intoxicated rats by increasing antioxidants levels with slight decreasing in MDA production compared to untreated group. This study suggested that Moringa oleifera extract could possibly restore the altered cardiac histopathology and some antioxidant power in AlP intoxicated rats, and it could even be used as adjuvant therapy against AlP-induced cardiotoxicity.

Bone allograft banking in South Australia.

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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.

Evaluation of renal allograft with 99mTc-mononuclear leukocytes

International Nuclear Information System (INIS)

Souza, S.A.L.; Oliveira, H.S.; Goncalves, R.T.; Pontes, D.S.; Fonseca, L.B.M.; Gutfilen, B.

2002-01-01

Aim: Because kidney biopsy is an invasive procedure that carries a small but significant risk of major complications, a noninvasive test that detects rejection before it is clinically apparent is very much needed. The reversibility of acute rejection is related to the promptness with which treatment is begun. Here we show the evaluation of rejection in the first week post-transplant with 99m Tc-mononuclear leukocyte scintigraphy (99mTc-MLS). Materials and Methods: 70 patients submitted to renal transplant at the Hospital Universitario Clementino Fraga Filho (HUCFF/UFRJ) underwent 99m Tc-MLS at the 1st and 5th post-transplant days. The labeled cells were administered (444MBq) and scans were carried out 3 and 24h post injection. A region of interest (ROI) was drawn at the allograft image and statistics compared between the 3 and 24h images. Percentages above 15% in the 24h image relating to the 3h image were considered abnormal and suspect of rejection. 25 of the 70 patients rejected the renal allograft in the 1st week post-transplant. Results: 99m Tc-MLS has detected rejection in 20 of the 25 patients. Color Doppler was also carried out in all the patients and has detected 16 rejections. Sensitivity and specificity were 80% and 100% for scintigraphy and 64% and 100% for Ultrasound. 99m Tc-MLS is more sensitive in humoral rejection than color Doppler. The latter is better to identify the vascular rejection. Conclusion: In order to evaluate renal allograft and improve the rejection diagnosis the combination of both techniques should be applied. More studies are now in progress

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.

Urine Biochemistry in the Early Postoperative Period after Cardiac Surgery: Role in Acute Kidney Injury Monitoring

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Alexandre Toledo Maciel

2013-01-01

Full Text Available We have recently suggested that sequential urine electrolyte measurement in critically ill patients may be useful in monitoring kidney function. Cardiac surgery is one of the leading causes of acute kidney injury (AKI in the intensive care unit (ICU. In this paper, we describe the sequential behavior of urine electrolytes in three patients in the early (first 60 hours postoperative period after cardiac surgery according to AKI status: no AKI, transient AKI, and persistent AKI. We have found that the patient with no AKI had stable and high concentrations of sodium (NaU and chloride (ClU in sequential spot samples of urine. AKI development was characterized in the other two patients by decreases in NaU and ClU, which have started early after ICU admission. Transient AKI was marked by also transient and less severe decreases in NaU and ClU. Persistent AKI was marked by the less favorable clinical course with abrupt and prolonged declines in NaU and ClU values. These electrolytes in urine had a behavior like a “mirror image” in comparison with that of serum creatinine. We suggest that sequential urine electrolytes are useful in monitoring acute kidney injury development in the early postoperative period after cardiac surgery.

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

Predictive value of routine point-of-care cardiac troponin T measurement for prehospital diagnosis and risk-stratification in patients with suspected acute myocardial infarction

DEFF Research Database (Denmark)

Rasmussen, Martin B; Stengaard, Carsten; Sørensen, Jacob T

2017-01-01

-of-care cardiac troponin T measurements (11.0%) had a value ≥50 ng/l, including 966 with acute myocardial infarction (sensitivity: 44.2%, specificity: 92.8%). Patients presenting with a prehospital point-of-care cardiac troponin T value ≥50 ng/l had a one-year mortality of 24% compared with 4.8% in those...... with values analysis: point-of-care cardiac troponin T≥50 ng/l (hazard ratio 2.10, 95% confidence interval: 1.90-2.33), congestive heart failure (hazard ratio 1.93, 95% confidence interval: 1......OBJECTIVE: The purpose of this study was to determine the predictive value of routine prehospital point-of-care cardiac troponin T measurement for diagnosis and risk stratification of patients with suspected acute myocardial infarction. METHODS AND RESULTS: All prehospital emergency medical service...

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

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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.

Basic vital cardiac support. Training to relatives of patients with acute miocardial infarction

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Brandy Viera Valdés; Paula Aguila Solis; Francisco Valladares Carvajal; Marcos D. Iraola Ferrer; Pablo. A. Rodríguez

2006-01-01

Background: Title: Basic vital cardiac support. Training to relatives of patients with acute miocardial infarction. The cardiorespiratory reanimation is a proved procedure that can save a human life in case of a cardiorespiratory stop. For three years it is imparted in the University Hospital of Cienfuegos, a training for this procedure, to the family of patients with sharp myocardic infarction. Objective: To evaluate the knowledge acquired by the relatives of the patients during the training...

Cardiac arrhythmia as initial presentation of aneurysmal subarachnoid hemorrhage

NARCIS (Netherlands)

van der Kleij, FGH; Henselmans, JML; van de Loosdrecht, AA

1999-01-01

Cardiac arrhythmia and sudden death are most frequently caused by preexisting heart disease. Rarely, cardiac arrhythmia is a first symptom of an acute neurological event. We describe a patient with asystole and other cardiac arrhythmias, as initial symptoms of acute aneurysmal subarachnoid

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

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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

Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5T MR.

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Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J; Schuster, Frederick; Riva, Fabiano; Zech, Wolf-Dieter

2017-01-01

Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DIAGNOSTIC EFFICACY OF CARDIAC TROPONIN-T IN ACUTE MYOCARDIAL INFARCTION PATIENTS ADMITTED IN INTENSIVE CARDIAC CARE UNIT

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Tapan

2016-03-01

Full Text Available INTRODUCTION Myocardial infarction is a common and severe manifestation of ischaemic heart disease (IHD. Acute myocardial infarction (AMI is the result of death of heart muscle cells following either from a prolonged or severe ischaemia. The World Health Organisation emphasises IHD as our "Modern Epidemic" and AMI as common cause of sudden death. AIM The present study has been undertaken with the aim to assess the role of cardiac Troponin-T in early diagnosis of AMI and to evaluate its positive roles over CK-MB and LDH enzyme assays. The study also aims to find out the role of cardiac Troponin-T test, where ECG changes are nondiagnostic and inconclusive for AMI. MATERIAL & METHOD One hundred cases of provisionally diagnosed AMI, who were admitted during June 2012 to July 2015 in ICC Unit of TMC & Dr. BRAM Teaching Hospital, formed the subjects for the study. Those patients reported 2 to 10 hours after onset of chest pain were included in this study. Patients reported beyond 10 hours after onset of chest pain of AMI cases and patients having chest pain of non-AMI causes are excluded from the study. The provisional diagnosis of AMI was done on the basis of the history, chest pain, clinical findings and ECG changes. Trop-T test (Troponin-T sensitive rapid test by Muller Bardoff, et al, 1991 as well as CK-MB (creatine kinase-MB isoenzymeassays were performed immediately for each and every patient. Trop-T test was repeated in some selective cases where the early changes were insignificant and the results were compared with those of CK-MB, at different period of the disease onset. RESULTS The rapid cardiac Troponin-T test (CTn-T has 100% specificity for AMI whereas CK-MB and LDH have specificities of 80% and 60% respectively. The CTn-T has diagnostic efficiency of 92% for AMI but ECG has only 69% sensitivity and 80% specificity. The overall diagnostic efficacy of cardiac Troponin-T is higher than that of CK-MB, LDH and ECG (94% versus 92%, 91 % and 72

Mechanisms of immunologic unresponsiveness induced by ultraviolet-irradiated donor-specific blood transfusions and peritransplant cyclosporine

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Oluwole, S.F.; Chabot, J.; Pepino, P.; Reemtsma, K.; Hardy, M.A.

1988-09-01

Recipient pretreatment with UV-B irradiated donor-specific blood transfusions (UV-DST) combined with peritransplant cyclosporine on days 0, +1, and +2 leads to permanent cardiac allograft survival in the ACI-to-Lewis rat strain combination. This study investigates the mechanisms of immunologic unresponsiveness induced by UV-DST and CsA by examining several in vitro and in vivo parameters in long-term cardiac allograft recipients. The results of the in vitro studies demonstrate that thoracic duct lymphocytes (TDL) of treated and allografted Lewis rats respond less in a mixed lymphocyte reaction to donor splenic lymphocytes (SpL) by 69%, 75%, and 73% (P less than 0.001) at 30, 50, and 100 days after transplantation, respectively, compared with controls, while the response to a third-party (W/F) SpL is unimpaired. In coculture experiments, the TDL from treated recipients specifically suppressed the response of unmodified Lewis TDL to ACI SpL by 59% and 40% (P less than 0.01) at 30 and 50 days after transplantation, respectively, while responses to W/F SpL were suppressed by only 3-6%. The sera obtained from ungrafted rats transfused with UV-DST suppressed the MLR between unmodified Lewis TDL and ACI SpL by 31% (P less than 0.05) while the sera from UV-DST and CsA-treated and allografted rats specifically suppressed the MLR by 75%, 80% (P less than 0.001) and 37% (P less than 0.01) at 10, 30, and 50 days after transplantation, respectively. In vivo adoptive transfer of 10(4) donor-type dendritic cells (DC) into recipients of beating cardiac allografts at 40 or 60 days after transplantation led to rapid and acute allograft rejection, while the adoptive transfer of 10(8) unseparated SpL obtained at 50 days after transplantation from treated Lewis recipients to syngeneic naive hosts led to a modest but significant prolongation of ACI test cardiac allografts.

Uncemented allograft-prosthetic composite reconstruction of the proximal femur

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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.

Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

DEFF Research Database (Denmark)

Craddock, Charles; Labopin, Myriam; Robin, Marie

2016-01-01

Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic...... syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients...... conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required....

Intrathymic immune modulation prevents acute rejection but not the development of graft arteriosclerosis (chronic rejection)

NARCIS (Netherlands)

Hillebrands, JL; Raue, HP; Klatter, FA; Hylkema, MN; Platteel, [No Value; Hardonk-Wubbena, A; Nieuwenhuis, P; Rozing, J

2001-01-01

Background. We showed previously that our intrathymic immune modulation protocol induces virtually permanent graft survival of simultaneously transplanted cardiac allografts in MHC-incompatible rat strain combinations. It is, however, unknown whether this procedure prevents the development of graft

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

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 ...

In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis.

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Xavier Helluy

Full Text Available Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis.Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast.This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise localization of

Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.

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Marta Miró-Murillo

Full Text Available Von Hippel Lindau (Vhl gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs, have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2. Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed-UBC-Cre-ER(T2 adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2 tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2 mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.

PREVENTION OF LEFT VENTRICLE SYSTOLIC DYSFUNCTION IN PATIENTS WITH ACUTE CORONARY SYNDROME WITH ST SEGMENT ELEVATION AFTER CARDIAC REVASCULARIZATION

OpenAIRE

A. L. Alyavi; B. A. Alyavi; M. L. Kenzhaev; S. R. Kenzhaev

2009-01-01

Aim. To study effects of bioflavonoid quercetin (corvitin) on left ventricle (LV) systolic dysfunction in patients with acute coronary syndrome with ST segment elevation (ACS+ST) after cardiac revascularization.Material and methods. 60 patients with ACS+ST (44,2±1,3 y.o.) were examined. Patients were admitted to hospital within 6 hours after complaints beginning. Patients were randomized in two groups. 30 patients of group A had standard therapy and cardiac revascularization. 30 patients of g...

Acute effect of Vagus nerve stimulation parameters on cardiac chronotropic, inotropic, and dromotropic responses

Science.gov (United States)

Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

2017-11-01

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy and depression, and is considered as a potential therapy for other pathologies, including Heart Failure (HF) or inflammatory diseases. In the case of HF, several experimental studies on animals have shown an improvement in the cardiac function and a reverse remodeling of the cardiac cavity when VNS is applied. However, recent clinical trials have not been able to reproduce the same response in humans. One of the hypothesis to explain this lack of response is related to the way in which stimulation parameters are defined. The combined effect of VNS parameters is still poorly-known, especially in the case of VNS synchronously delivered with cardiac activity. In this paper, we propose a methodology to analyze the acute cardiovascular effects of VNS parameters individually, as well as their interactive effects. A Latin hypercube sampling method was applied to design a uniform experimental plan. Data gathered from this experimental plan was used to produce a Gaussian process regression (GPR) model in order to estimate unobserved VNS sequences. Finally, a Morris screening sensitivity analysis method was applied to each obtained GPR model. Results highlight dominant effects of pulse current, pulse width and number of pulses over frequency and delay and, more importantly, the degree of interactions between these parameters on the most important acute cardiovascular responses. In particular, high interacting effects between current and pulse width were found. Similar sensitivity profiles were observed for chronotropic, dromotropic and inotropic effects. These findings are of primary importance for the future development of closed-loop, personalized neuromodulator technologies.

Pain and Anxiety in Rural Acute Coronary Syndrome Patients Awaiting Diagnostic Cardiac Catheterization.

Science.gov (United States)

O'Keefe-McCarthy, Sheila; McGillion, Michael; Clarke, Sean P; McFetridge-Durdle, Judith

2015-01-01

In rural areas of Canada, people with acute coronary syndromes (ACS) can wait up to 32 hours for transfer for diagnostic cardiac catheterization (CATH). While awaiting CATH, it is critical that pain and anxiety management be optimal to preserve myocardial muscle and minimize the risk of further deterioration. The aim of this study was to examine the relationship between clinical management, cardiac pain intensity, and state anxiety for rural ACS patients awaiting diagnostic CATH. In a prospective, descriptive-correlational repeated-measures design involving 121 ACS rural patients, we examined the associations of analgesic and nitroglycerin administration with cardiac pain intensity (numeric rating scale) and state anxiety (Spielberger State Anxiety Inventory) and also nurses' pain knowledge and attitudes (Toronto Pain Management Inventory-ACS Version and Knowledge and Attitudes Survey Regarding Pain) using linear mixed models. The mean age of patients was 67.6 ± 13, 50% were men, and 60% had unstable angina and the remainder had non-ST-elevated myocardial infarction. During follow-up, cardiac pain intensity scores remained in the mild range from 1.1 ± 2.2 to 2.4 ± 2.7. State anxiety ranged from 44.0 ± 7.2 to 46.2 ± 6.6. Cumulative analgesic dose was associated with a reduction in cardiac pain by 1.0 points (numeric rating scale, 0-10) (t108 = -2.5; SE, -0.25; confidence interval, -0.45 to -0.06; P = .013). Analgesic administration was not associated with state anxiety. Over the course of follow-up, ACS patients reported consistently high anxiety scores. Whereas cardiac pain declines in most patients in the early hours after admission, many patients experience a persistent anxious state up to 8 hours later, which suggest that development and testing of protocols for anxiety reduction may be needed. More urgently, the development and examination of a treatment intervention, early on in the ACS trajectory, are warranted that targets pain and anxiety for those for

[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.

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

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

Two acute kidney injury risk scores for critically ill cancer patients undergoing non-cardiac surgery.

Science.gov (United States)

Xing, Xue-Zhong; Wang, Hai-Jun; Huang, Chu-Lin; Yang, Quan-Hui; Qu, Shi-Ning; Zhang, Hao; Wang, Hao; Gao, Yong; Xiao, Qing-Ling; Sun, Ke-Lin

2012-01-01

Several risk scoures have been used in predicting acute kidney injury (AKI) of patients undergoing general or specific operations such as cardiac surgery. This study aimed to evaluate the use of two AKI risk scores in patients who underwent non-cardiac surgery but required intensive care. The clinical data of patients who had been admitted to ICU during the first 24 hours of ICU stay between September 2009 and August 2010 at the Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively collected and analyzed. AKI was diagnosed based on the acute kidney injury network (AKIN) criteria. Two AKI risk scores were calculated: Kheterpal and Abelha factors. The incidence of AKI was 10.3%. Patients who developed AKI had a increased ICU mortality of 10.9% vs. 1.0% and an in-hospital mortality of 13.0 vs. 1.5%, compared with those without AKI. There was a significant difference between the classification of Kheterpal's AKI risk scores and the occurrence of AKI (PAbelha's AKI risk scores and the occurrence of AKI (P=0.499). Receiver operating characteristic curves demonstrated an area under the curve of 0.655±0.043 (P=0.001, 95% confidence interval: 0.571-0.739) for Kheterpal's AKI risk score and 0.507±0.044 (P=0.879, 95% confidence interval: 0.422-0.592) for Abelha's AKI risk score. Kheterpal's AKI risk scores are more accurate than Abelha's AKI risk scores in predicting the occurrence of AKI in patients undergoing non-cardiac surgery with moderate predictive capability.

Sudden cardiac death: the pro-arrhythmic interaction of an acute loading with an underlying substrate.

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Sutherland, George R

2017-10-21

Sudden cardiac death (SCD) is a complex phenomenon, occurring either in apparently normal individuals or in those where there is a recognized underlying cardiac abnormality. In both groups, the lethal arrhythmia has frequently been related to the physiologic trigger of either exercise or stress. Prior research into SCD has focused mainly on a combination of identifying either vulnerable myocardial substrates; pharmacological approaches to altering electrical activation/repolarisation in substrates; or the suppression of induced lethal arrhythmias with implantable defibrillators. However, it has been suggested that in a significant number of cases, the interaction of a transient induced trigger with a pre-existing electrical or mechanical substrate is the basis for the induction of the sustained lethal arrhythmia. In this manuscript we will discuss the precise mechanisms whereby one of such potential physiologic trigger: an acute change in systolic blood pressure, can induce a sequence of alterations in global and local cardiac mechanics which in turn result in regional left ventricular post-systolic deformation which, mediated (through stretch-induced changes in local mechano-electrical coupling) provokes local electrical after-depolarisations which can spill over into complex runs of premature ventricular beats. These local acute pressure/stretch induced runs of ventricular ectopy originate in either basal or apical normal myocardium and, in combination with a co-existing distal pro-arrhymic substrate, can interact to induce a lethal arrhythmia. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

A ten years experience with allograft implantation

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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

The HEART score is useful to predict cardiovascular risks and reduces unnecessary cardiac imaging in low-risk patients with acute chest pain.

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Dai, Siping; Huang, Bo; Zou, Yunliang; Guo, Jianbin; Liu, Ziyong; Pi, Dangyu; Qiu, Yunhong; Xiao, Chun

2018-06-01

The present study was to investigate whether the HEART score can be used to evaluate cardiovascular risks and reduce unnecessary cardiac imaging in China.Acute coronary syndrome patients with the thrombosis in myocardial infarction risk score risk HEART score group and 2 patients (1.5%) in the high risk HEART score group had cardiovascular events. The sensitivity of HEART score to predict cardiovascular events was 100% and the specificity was 46.7%. The potential unnecessary cardiac testing was 46.3%. Cox proportional hazards regression analysis showed that per one category increase of the HEART score was associated with nearly 1.3-fold risk of cardiovascular events.In the low-risk acute chest pain patients, the HEART score is useful to physicians in evaluating the risk of cardiovascular events within the first 30 days. In addition, the HEART score is also useful in reducing the unnecessary cardiac imaging.

Effect of short-term intensive atorvastatin treatment on interventional treatment effect and cardiac function of patients with acute coronary syndrome

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Yu Lei

2016-06-01

Full Text Available Objective: To study the effect of short-term intensive atorvastatin treatment on interventional treatment effect and cardiac function of patients with acute coronary syndrome. Methods: A total of 104 cases of patients with acute coronary syndrome who received PCI treatment in Emergency Department of our hospital from May 2014 to November 2015 were retrospectively analyzed and divided into intensive group and routine group according to different atorvastatin treatment methods, and then biochemical indexes, cardiac ultrasound indicators and inflammatory indexes of two groups were compared. Results: Serum TG, TC, LDL-C, hs- CRP, LDH, α-HBDH, CK and CK-MB content of intensive group were significantly lower than those of routine group while HDL-C content was higher than that of routine group; E/ A ratio and LVEF of intensive group were higher than those of routine group while Tei index, systolic index and diastolic index were lower than those of routine group; TLR4 and NF-kB expression levels in peripheral blood as well as TNF-α and IL-6 content in serum of intensive group were significantly lower than those of routine group. Conclusion: Short-term intensive atorvastatin treatment improves the interventional treatment effect of patients with acute coronary syndrome, and can reduce myocardial injury, improve cardiac diastolic and systolic function and inhibit the inflammation mediated by TLR4/NF-kB.

Mast cell degranulation breaks peripheral tolerance.

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de Vries, V C; Wasiuk, A; Bennett, K A; Benson, M J; Elgueta, R; Waldschmidt, T J; Noelle, R J

2009-10-01

Mast cells (MC) have been shown to mediate regulatory T-cell (T(reg))-dependent, peripheral allograft tolerance in both skin and cardiac transplants. Furthermore, T(reg) have been implicated in mitigating IgE-mediated MC degranulation, establishing a dynamic, reciprocal relationship between MC and T(reg) in controlling inflammation. In an allograft tolerance model, it is now shown that intragraft or systemic MC degranulation results in the transient loss of T(reg) suppressor activities with the acute, T-cell dependent rejection of established, tolerant allografts. Upon degranulation, MC mediators can be found in the skin, T(reg) rapidly leave the graft, MC accumulate in the regional lymph node and the T(reg) are impaired in the expression of suppressor molecules. Such a dramatic reversal of T(reg) function and tissue distribution by MC degranulation underscores how allergy may causes the transient breakdown of peripheral tolerance and episodes of acute T-cell inflammation.

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

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

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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.

Perspectives of Post-Acute Transition of Care for Cardiac Surgery Patients

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Nicoleta Stoicea

2017-11-01

Full Text Available Post-acute care (PAC facilities improve patient recovery, as measured by activities of daily living, rehabilitation, hospital readmission, and survival rates. Seamless transitions between discharge and PAC settings continue to be challenges that hamper patient outcomes, specifically problems with effective communication and coordination between hospitals and PAC facilities at patient discharge, patient adherence and access to cardiac rehabilitation (CR services, caregiver burden, and the financial impact of care. The objective of this review is to examine existing models of cardiac transitional care, identify major challenges and social factors that affect PAC, and analyze the impact of current transitional care efforts and strategies implemented to improve health outcomes in this patient population. We intend to discuss successful methods to address the following aspects: hospital-PAC linkages, improved discharge planning, caregiver burden, and CR access and utilization through patient-centered programs. Regular home visits by healthcare providers result in decreased hospital readmission rates for patients utilizing home healthcare while improved hospital-PAC linkages reduced hospital readmissions by 25%. We conclude that widespread adoption of improvements in transitional care will play a key role in patient recovery and decrease hospital readmission, morbidity, and mortality.

Allografts versus Equine Xenografts in Calcaneal Fracture Repair.

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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.

Head-to-head comparison of cardiac troponin T and troponin I in patients without acute coronary syndrome

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Árnadóttir, Ásthildur; Falk Klein, Christine; Iversen, Kasper

2017-01-01

BACKGROUND: Cardiac-specific troponin T (cTnT) and troponin I (cTnI) are considered diagnostically equal in patients with acute coronary syndrome (ACS). The aim of this systematic review was to compare the prevalence and prognostic strength of elevations of cTnT and cTnI in patients with other...

Role of Soluble ST2 as a Marker for Rejection after Heart Transplant

OpenAIRE

Lee, Ga Yeon; Choi, Jin-Oh; Ju, Eun-Seon; Lee, Yoo-Jung; Jeon, Eun-Seok

2016-01-01

Background and Objectives Endomyocardial biopsy is obligatory during the first year after heart transplant (HTx) for the surveillance of acute rejection. Previous attempts using cardiac biomarkers for the detection of rejection failed to show enough evidence to substitute endomyocardial biopsy. Therefore, this study sought the possibility of using soluble ST2 (sST2), a novel cardiovascular marker, as a surrogate marker for acute allograft rejection after HTx. Subjects and Methods A total of 4...

Significant prolongation of segmental pancreatic allograft survival in two species

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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.

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

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.

Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection.

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Lionel Lattenist

Full Text Available The Endothelial Protein C Receptor (EPCR is expressed on leukocytes, on endothelium of large blood vessels and to a lesser extent on capillaries. Membrane bound EPCR plays an important role in the activation of protein C which has anticoagulant, anti-inflammatory and cytoprotective effects. After cleavage by a protease EPCR is also found as a soluble protein. Acute rejection of kidney allografts can be divided in T-cell-mediated rejection (TCMR and antibody-mediated (ABMR rejection. The latter is characterized by strong activation of coagulation. Currently no reliable non-invasive biomarkers are available to monitor rejection. Renal biopsies were available from 81 renal transplant patients (33 without rejection, 26 TCMR and 22 ABMR, we had access to mRNA material, matched plasma and urine samples for a portion of this cohort. Renal EPCR expression was assessed by RT-PCR and immunostaining. Plasma and urine sEPCR levels were measured by ELISA. ABMR patients showed higher levels of EPCR mRNA than TCMR patients. EPCR expression on glomeruli was significantly elevated in ABMR patients than in TCMR or control patients. In the peritubular capillaries EPCR expression was higher in ABMR patients than in control patients. EPCR expression was higher in tubules and arteries of rejection patients than in control patients. Plasma sEPCR levels did not differ. Urine sEPCR levels were more elevated in the ABMR group than in patients with TCMR or without rejection. ROC analysis demonstrated that urinary sEPCR is appropriate to discriminate between ABMR patients and TCMR or control patients. We conclude that urinary sEPCR could be a novel non-invasive biomarker of antibody mediated rejection in renal transplantation.

History of osteochondral allograft transplantation.

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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.

Renal ultrasound provides low utility in evaluating cardiac surgery associated acute kidney injury.

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Young, Allen; Crawford, Todd; Pierre, Alejandro Suarez; Trent Magruder, J; Fraser, Charles; Conte, John; Whitman, Glenn; Sciortino, Christopher

2017-09-02

Renal ultrasonography is part of the algorithm in assessing acute kidney injury (AKI). The purpose of this study was to assess the clinical utility of renal US in postoperative cardiac patients who develop AKI. We conducted a retrospective study of 90 postoperative cardiac surgery patients at a single institution from 1/19/2010 to 3/19/2016 who underwent renal US for AKI. We reviewed provider documentation to determine whether renal US changed management. We defined change as: administration of crystalloid or colloid, addition of inotropic or vasopressor, or procedural interventions on the renal system. Mean age of study patients was 68 ± 13 years. 48/90 patients (53.3%) had pre-existing chronic kidney disease of varying severity. 48 patients (53.3%) had normal renal US with incidental findings and 31 patients (34.4%) had US evidence of medical kidney disease. 10 patients (11.1%) had limited US results due to poor visualization and 1 patient (1.1%) had mild right-sided hydronephrosis. No patients were found to have obstructive uropathy or renal artery stenosis. Clinical management was altered in only 4/90 patients (4.4%), which included 3 patients that received a fluid bolus and 1 patient that received a fluid bolus and inotropes. No vascular or urologic procedures resulted from US findings. Although renal ultrasound is often utilized in the work-up of AKI, our study shows that renal US provides little benefit in managing postoperative cardiac patients. This diagnostic modality should be scrutinized rather than viewed as a universal measure in the cardiac surgery population.

Acute pancreatitis induced by mycophenolate mofetil in a kidney transplant patient

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Einollahi Behzad

2015-04-01

Full Text Available Acute pancreatitis is a rare life-threatening complication in patients after kidney transplantation. Here we described a 56-year-old man who had received a living related kidney transplant for an end-stage renal disease. In his regular follow-up, his serum creatinine was gradually increased and he underwent an allograft biopsy, which revealed an interstitial nephritis/tubular atrophy grade II. Mycophenolate mofetil (MMF was prescribed to control chronic allograft nephropathy. He presented with complaints of severe abdominal pain, vomiting, loss of appetite and fever requiring hospital admission twelve days later. Acute pancreatitis was diagnosed on the basis of laboratory data and imaging findings during hospital admission. There was no history of alcohol consumption in our patient. Unfortunately he died one week later and autopsy findings demonstrated acute necrotizing pancreatitis. The bladder drainage of this patients was normal. Laboratory findings in this patient did not endorse infections and other possibilities regarding the etiology of acute pancreatitis in this patient. Therefore, we concluded that acute pancreatitis in near the patient was induced by drugs and basis on our evidence, MMF is the most important suspect. This study suggests that acute pancreatitis can be considered as a side effect of MMF.

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

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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.

Percutaneous Vertebral Augmentation with Polyethylene Mesh and Allograft Bone for Traumatic Thoracolumbar Fractures

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C. Schulz

2015-01-01

Full Text Available Purpose. In cases of traumatic thoracolumbar fractures, percutaneous vertebral augmentation can be used in addition to posterior stabilisation. The use of an augmentation technique with a bone-filled polyethylene mesh as a stand-alone treatment for traumatic vertebral fractures has not yet been investigated. Methods. In this retrospective study, 17 patients with acute type A3.1 fractures of the thoracic or lumbar spine underwent stand-alone augmentation with mesh and allograft bone and were followed up for one year using pain scales and sagittal endplate angles. Results. From before surgery to 12 months after surgery, pain and physical function improved significantly, as indicated by an improvement in the median VAS score and in the median pain and work scale scores. From before to immediately after surgery, all patients showed a significant improvement in mean mono- and bisegmental kyphoses. During the one-year period, there was a significant loss of correction. Conclusions. Based on this data a stand-alone approach with vertebral augmentation with polyethylene mesh and allograft bone is not a suitable therapy option for incomplete burst fractures for a young patient collective.

The Effect of Home-Based Cardiac Rehabilitation on Functional Capacity, Behavior, and Risk Factors in Patients with Acute Coronary Syndrome in China

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Rongjing Ding

2017-02-01

Full Text Available Aim: To investigate the effect of home-based cardiac rehabilitation on functional capacity, health behavior, and risk factors in patients with acute coronary syndrome in China. Methods: Eighty patients with acute coronary syndrome were enrolled in this prospective randomized controlled study. Patients in the cardiac rehabilitation group (n=52 received home-based cardiac rehabilitation with a heart manual and a home exercise video for 3 months and patients in the control group (n=28 received only routine secondary prevention. The 6-min walk distance, laboratory test results, healthy behavior (questionnaire, quality of life (12-item Short Form Health Survey, anxiety (7-item Generalized Anxiety Disorder Questionnaire, and depression (9-item Patient Health Questionnaire were evaluated at the beginning and after treatment for 3 months. Results: Compared with baseline data, 52 patients who participated in cardiac rehabilitation had longer 6-min walk distance (515.26±113.74 m vs 0.445.30±97.92 m, P<0.0002, higher proportions of “always exercise” (78.26% vs. 28%, P<0.05, “always limit food with sugar” (65.22% vs 12%, P<0.05, “always eat fruits 200–400 g every day” (82.61% vs. 4%, P<0.05. and “always eat vegetables 300–500 g every day” (21.74% vs. 12%, P<0.06 after treatment for 3 months. The low-density lipoprotein cholesterol control rate (52.17% vs. 28%, P<0.05 and the systolic blood pressure control rate (100% vs. 68%, P<0.05 were also significantly increased after treatment for 3 months in the cardiac rehabilitation group. No significant increase was found in the control group after treatment for 3 months. No cardiac-event related to home exercise was reported in both groups. Conclusion: Home-based cardiac rehabilitation is a feasible and available cardiac rehabilitation mode in China.

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

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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.

Implementing a working together model for Aboriginal patients with acute coronary syndrome: an Aboriginal Hospital Liaison Officer and a specialist cardiac nurse working together to improve hospital care.

Science.gov (United States)

Daws, Karen; Punch, Amanda; Winters, Michelle; Posenelli, Sonia; Willis, John; MacIsaac, Andrew; Rahman, Muhammad Aziz; Worrall-Carter, Linda

2014-11-01

Acute coronary syndrome (ACS) contributes to the disparity in life expectancy between Aboriginal and non-Aboriginal Australians. Improving hospital care for Aboriginal patients has been identified as a means of addressing this disparity. This project developed and implemented a working together model of care, comprising an Aboriginal Hospital Liaison Officer and a specialist cardiac nurse, providing care coordination specifically directed at improving attendance at cardiac rehabilitation services for Aboriginal Australians in a large metropolitan hospital in Melbourne. A quality improvement framework using a retrospective case notes audit evaluated Aboriginal patients' admissions to hospital and identified low attendance rates at cardiac rehabilitation services. A working together model of care coordination by an Aboriginal Hospital Liaison Officer and a specialist cardiac nurse was implemented to improve cardiac rehabilitation attendance in Aboriginal patients admitted with ACS to the cardiac wards of the hospital. A retrospective medical records audit showed that there were 68 Aboriginal patients admitted to the cardiac wards with ACS from 1 July 2008 to 30 June 2011. A referral to cardiac rehabilitation was recorded for 42% of these. During the implementation of the model of care, 13 of 15 patients (86%) received a referral to cardiac rehabilitation and eight of the 13 (62%) attended. Implementation of the working together model demonstrated improved referral to and attendance at cardiac rehabilitation services, thereby, has potential to prevent complications and mortality. WHAT IS KNOWN ABOUT THE TOPIC?: Aboriginal Australians experience disparities in access to recommended care for acute coronary syndrome. This may contribute to the life expectancy gap between Aboriginal and non-Aboriginal Australians. WHAT DOES THIS PAPER ADD?: This paper describes a model of care involving an Aboriginal Hospital Liaisons Officer and a specialist cardiac nurse working

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

Primary reconstruction of the lateral collateral ligament complex (LCLC) using graft tissue restores elbow stability in many, but not all, elbows with acute or chronic posterolateral rotatory instability (PLRI). Revision reconstruction using a tendon allograft is occasionally considered for persistent PLRI, but the outcome of revision ligament reconstruction in this setting is largely unknown. We determined whether revision allograft ligament reconstruction can (1) restore the stability and (2) result in improved elbow scores for patients with persistent PLRI of the elbow after a previous failed primary reconstructive attempt and in the context of the diverse pathology being addressed. Between 2001 and 2011, 160 surgical elbow procedures were performed at our institution for the LCLC reconstruction using allograft tissue. Only patients undergoing revision allograft reconstruction of the LCLC for persistent PLRI with a previous failed primary reconstructive attempt using graft tissue and at least I year of followup were included in the study. Eleven patients (11 elbows) fulfilled our inclusion criteria and formed our study cohort. The cohort consisted of six female patients and five male patients. The mean age at the time of revision surgery was 36 years (range, 14-59 years). The revision allograft reconstruction was carried out after a mean of 3 years (range, 2.5 months to 9 years) from a failed attempted reconstruction of the LCLC. Osseous deficiency to some extent was identified in the preoperative radiographs of eight elbows. Mean followup was 5 years (range, 1-12 years). Revision allograft reconstruction of the LCLC restored elbow stability in eight of the 11 elbows; two of the three elbows with persistent instability were operated on a third time (at 6 and 7 months after allograft revision reconstruction). For elbows with no persistent instability, the mean Mayo Elbow Performance Score at most recent followup was 83 points (range, 60-100 points), and

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

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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

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

Directory of Open Access Journals (Sweden)

Yuta Abe

transplantation, induces the formation of CD4(+ T-cells that are not themselves Tregs but give rise directly or indirectly to fully functional CD4(+CD45RC(-Foxp3(+Tregs when transferred into MHC mismatched recipients prior to LTx. These Tregs possess potent suppressive activity and are capable of suppressing acute liver allograft rejection. Understanding the mechanisms by which preoperative DST induces the generation of tolerogenic Tregs in the presence of alloantigens may lead to the development of novel antigen-specific immunological therapies for the treatment of solid organ rejection.

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

A case of acute paraplegia that improved with dialysis.

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Rajendiran, Govarthanan; Jayabalan, Rajamahesh; Chandrahasan, Saravanan; Mani, Ashwin Kumar

2008-01-01

Acute severe hyperkalemia can present as acute paraplegia independent of cardiac effects, even though cardiac muscle is more sensitive to serum potassium changes. We managed a patient with acute hyperkalemic paralysis who did not have threatening cardiac/electrocardiographic manifestations. The limb weakness became normal after hemodialysis.

In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

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Helluy, Xavier; Sauter, Martina; Ye, Yu-Xiang; Lykowsky, Gunthard; Kreutner, Jakob; Yilmaz, Ali; Jahns, Roland; Boivin, Valerie; Kandolf, Reinhard; Jakob, Peter M.; Hiller, Karl-Heinz; Klingel, Karin

2017-01-01

Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise

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

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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.

Time to shift from contemporary to high-sensitivity cardiac troponin in diagnosis of acute coronary syndromes

Directory of Open Access Journals (Sweden)

Jamshed J. Dalal

2016-11-01

Training and displaying the clinical algorithm depicting the role of hs-TnI assay in acute cardiac care units and in EDs are an efficient way to deliver the new standard of care to patients. Compared with contemporary troponin assays, the hs-cTn assay accelerates the diagnostic pathway to 0–1 h, thus reducing the time for diagnosis of NSTEMI and hence, its management.

Perioperative change in creatinine following cardiac surgery with cardiopulmonary bypass is useful in predicting acute kidney injury: a single-centre retrospective cohort study.

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Takaki, Shunsuke; Shehabi, Yahya; Pickering, John W; Endre, Zoltan; Miyashita, Tetsuya; Goto, Takahisa

2015-10-01

Acute kidney injury is common following cardiac surgery. Experimental models of acute kidney injury suggest that successful therapy should be implemented within 24-48 h of renal injury. However, it is difficult to detect acute kidney injury shortly after cardiac surgery, because creatinine concentration is diluted by cardiopulmonary bypass. We hypothesized that, following cardiopulmonary bypass, creatinine reduction ratios would correlate with haematocrit reduction ratios and would be associated with the incidence of acute kidney injury. We collected demographic and blood test data from consecutive patients (n = 1137) who had undergone cardiac surgery with cardiopulmonary bypass. The creatinine reduction ratio was calculated as follows: (preoperative creatinine-postoperative creatinine)/preoperative creatinine. Patients were assigned to either of two groups. The first group (Group 1) was used to determine the threshold for acute kidney injury, and the second group (Group 2) was used to assess diagnostic performance. Acute kidney injury was defined as an increase in serum creatinine level >0.3 mg/dl or >150% from baseline. The incidence of acute kidney injury was 14.5% (79/545) in Group 1 and 15.5% (92/592) in Group 2. Postoperatively, creatinine concentration correlated strongly with haematocrit concentration (Pearson's r(2): 0.91). In Group 1, the area under the receiver operating characteristic curve, sensitivity and specificity were 0.71, 64.1 and 66.4%, respectively, for creatinine reduction ratios of creatinine reduction ratio performance were 4.3 (95% confidence interval 2.6-7.0), 0.27 (0.21-0.32), 0.92 (0.89-0.95) and 3.42 (2.22-5.27), respectively. The creatinine reduction ratio may be associated with perioperative renal injury. Therefore, it is a good diagnostic indicator with high performance, and may be useful in detecting acute kidney injury at an earlier stage relative to conventional means. In addition, using creatinine reduction ratios in this manner

Assessment of nerve regeneration across nerve allografts treated with tacrolimus.

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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.

A Case Report of Parvovirus B19 Infection in a Renal Allograft.

Science.gov (United States)

Oramas, Diana M; Setty, Suman; Yeldandi, Vijay; Cabrera, Julio; Patel, Tushar

2017-10-01

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.

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.

Hyperkalemia masked by pseudo-stemi infarct pattern and cardiac arrest.

Science.gov (United States)

Peerbhai, Shareez; Masha, Luke; DaSilva-DeAbreu, Adrian; Dhoble, Abhijeet

2017-12-01

Hyperkalemia is a common electrolyte abnormality and has well-recognized early electrocardiographic manifestations including PR prolongation and symmetric T wave peaking. With severe increase in serum potassium, dysrhythmias and atrioventricular and bundle branch blocks can be seen on electrocardiogram. Although cardiac arrest is a worrisome consequence of untreated hyperkalemia, rarely does hyperkalemia electrocardiographically manifest as acute ischemia. We present a case of acute renal failure complicated by malignant hyperkalemia and eventual ventricular fibrillation cardiac arrest. Recognition of this disorder was delayed secondary to an initial ECG pattern suggesting an acute ST segment elevation myocardial infarction (STEMI). Emergent coronary angiography performed showed no evidence of coronary artery disease. Pseudo-STEMI patterns are rarely seen in association with acute hyperkalemia and are most commonly described with patient without acute cardiac symptomatology. This is the first such case presenting concurrently with cardiac arrest. A brief review of this rare pseudo-infarct pattern is also given.

What to do when you question cardiac troponin values

DEFF Research Database (Denmark)

Mair, Johannes; Lindahl, Bertil; Müller, Christian

2017-01-01

High-sensitivity cardiac troponin assays enable cardiac troponin measurement with a high degree of analytical sensitivity and a low level of analytical imprecision at the low measuring range. One of the most important advantages of these new assays is that they allow novel, more rapid approaches...... for ruling in or ruling out acute myocardial infarctions. The increase in the early diagnostic sensitivity of high-sensitivity cardiac troponin assays comes at the cost of a reduced acute myocardial infarction specificity of the biomarker, because more patients with other causes of acute or chronic...... of the work-up for such a clinical setting....

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

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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.

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

Impact of specimen adequacy on the assessment of renal allograft biopsy specimens.

Science.gov (United States)

Cimen, S; Geldenhuys, L; Guler, S; Imamoglu, A; Molinari, M

2016-01-01

The Banff classification was introduced to achieve uniformity in the assessment of renal allograft biopsies. The primary aim of this study was to evaluate the impact of specimen adequacy on the Banff classification. All renal allograft biopsies obtained between July 2010 and June 2012 for suspicion of acute rejection were included. Pre-biopsy clinical data on suspected diagnosis and time from renal transplantation were provided to a nephropathologist who was blinded to the original pathological report. Second pathological readings were compared with the original to assess agreement stratified by specimen adequacy. Cohen's kappa test and Fisher's exact test were used for statistical analyses. Forty-nine specimens were reviewed. Among these specimens, 81.6% were classified as adequate, 6.12% as minimal, and 12.24% as unsatisfactory. The agreement analysis among the first and second readings revealed a kappa value of 0.97. Full agreement between readings was found in 75% of the adequate specimens, 66.7 and 50% for minimal and unsatisfactory specimens, respectively. There was no agreement between readings in 5% of the adequate specimens and 16.7% of the unsatisfactory specimens. For the entire sample full agreement was found in 71.4%, partial agreement in 20.4% and no agreement in 8.2% of the specimens. Statistical analysis using Fisher's exact test yielded a P value above 0.25 showing that - probably due to small sample size - the results were not statistically significant. Specimen adequacy may be a determinant of a diagnostic agreement in renal allograft specimen assessment. While additional studies including larger case numbers are required to further delineate the impact of specimen adequacy on the reliability of histopathological assessments, specimen quality must be considered during clinical decision making while dealing with biopsy reports based on minimal or unsatisfactory specimens.

Cardiac CT diagnosis in acute coronary syndrome. Significance of delayed enhancement effect in myocardium

International Nuclear Information System (INIS)

Yamaguchi, Takayoshi

2007-01-01

Authors have found that the effect in the title (DEE) exists in cardiac CT images due to the contrasting agent used for percutaneous coronary intervention (PCI) done shortly after the onset of acute coronary syndrome (ACS). To confirm the finding, they compared images of the cardiac CT and blood flow single photon emission computed tomography (SPECT) obtained several days after ACS. The cardiac CT images of 17 patients (M 15, F 2; average age 63.6 y) with ACS were obtained 20-30 min after the successfully attained emergent enhanced PCI, with the 4-row multi detector low CT (MDCT) machine Aquilion (Toshiba) in synchronization to R-R interval for processing to multiplanar reconstructed (MPR) images. Thereafter (5.5 days in average), myocardial SPECT was conducted with 99m Tc-tetrofosmin (740 MBq), of which images were also processed to MPR ones. The CT and SPECT images were compared in coronary arterial territories assigned to 17 segments in the left ventricle and to 20 areas in the Bull's-eye Map. Findings due to DEE in the former CT images were confirmed well correspondent with the lesion found in the latter SPECT, indicating that DEE is a useful tool for evaluation of ACS severity. (R.T.)

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.

Influence of the definition of acute renal failure post-cardiac surgery on incidence, patient identification, and identification of risk factors

NARCIS (Netherlands)

Noyez, L.

2011-01-01

OBJECTIVE: Acute renal failure post-cardiac surgery (RF) is a major complication and is associated with increased postoperative morbidity and mortality. Early recognition and identification of risk factors for RF is therefore important. However, several definitions of RF are used. The intention of

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....

Estimated glomerular filtration rate is an early biomarker of cardiac surgery-associated acute kidney injury.

Science.gov (United States)

Candela-Toha, Ángel; Pardo, María Carmen; Pérez, Teresa; Muriel, Alfonso; Zamora, Javier

2018-04-20

and objective Acute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. Using a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3,962 cases was divided into 2groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. AKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. Postoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Cardiac magnetic resonance assessment of takotsubo cardiomyopathy

International Nuclear Information System (INIS)

Abbas, A.; Sonnex, E.; Pereira, R.S.; Coulden, R.A.

2016-01-01

Takotsubo cardiomyopathy is an important condition that can be difficult to differentiate from acute coronary syndrome on the basis of clinical, electrocardiogram, and cardiac enzyme assessment alone. Although coronary angiography remains important in the acute assessment of patients with suspected takotsubo cardiomyopathy, cardiac magnetic resonance (CMR) has emerged over the last decade as an important non-invasive imaging tool in the diagnosis and follow-up of this condition. We present a review highlighting the CMR features of takotsubo cardiomyopathy and its complications with particular focus on differentiating this condition from acute myocardial infarction and myocarditis.

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

Extracorporeal Life Support and New Therapeutic Strategies for Cardiac Arrest Caused by Acute Myocardial Infarction - a Critical Approach for a Critical Condition

Directory of Open Access Journals (Sweden)

Benedek Theodora

2016-10-01

Full Text Available This review summarizes the most recent developments in providing advanced supportive measures for cardiopulmonary resuscitation, and the results obtained using these new therapies in patients with cardiac arrest caused by acute myocardial infarction (AMI. Also detailed are new approaches such as extracorporeal cardiopulmonary resuscitation (ECPR, intra-arrest percutaneous coronary intervention, or the regional models for systems of care aiming to reduce the critical times from cardiac arrest to initiation of ECPR and coronary revascularization.

Predischarge maximal exercise test identifies risk for cardiac death in patients with acute myocardial infarction

DEFF Research Database (Denmark)

Nielsen, J R; Mickley, H; Damsgaard, E M

1990-01-01

A maximal exercise test was performed in 54 patients with acute myocardial infarction (AMI) before discharge and in 49 age-matched control subjects. The long-term prognosis was assessed after an average follow-up of 7.6 years in AMI patients and 5.8 years in control subjects. The maximal work...... capacity and systolic blood pressure increase in AMI patients was 59% that of control subjects (p less than 0.001). Seventeen AMI patients had significant ST-segment shifts, 13 with ST depression and 4 with ST elevation. In AMI patients experiencing a cardiac death during follow-up the maximal work...... were of no significant value. In this study maximal work capacity turned out to be the best single exercise variable for identifying groups of AMI patients with very low and relative high risk of cardiac death. When all 3 exercise variables were combined, the predischarge maximal exercise test...

Response of cardiac endothelial nitric oxide synthase to plasma viscosity modulation in acute isovolemic hemodilution

Directory of Open Access Journals (Sweden)

Kanyanatt Kanokwiroon

2014-01-01

Full Text Available Background: Endothelial nitric oxide synthase (eNOS is generally expressed in endocardial cells, vascular endothelial cells and ventricular myocytes. However, there is no experimental study elucidating the relationship between cardiac eNOS expression and elevated plasma viscosity in low oxygen delivery pathological conditions such as hemorrhagic shock-resuscitation and hemodilution. This study tested the hypothesis that elevated plasma viscosity increases cardiac eNOS expression in a hemodilution model, leading to positive effects on cardiac performance. Materials and Methods: Two groups of golden Syrian hamster underwent an acute isovolemic hemodilution where 40% of blood volume was exchanged with 2% (low-viscogenic plasma expander [LVPE] or 6% (high-viscogenic plasma expander [HVPE] of dextran 2000 kDa. In control group, experiment was performed without hemodilution. All groups were performed in awake condition. Experimental parameters, i.e., mean arterial blood pressure (MAP, heart rate, hematocrit, blood gas content and viscosity, were measured. The eNOS expression was evaluated by eNOS Western blot analysis. Results: After hemodilution, MAP decreased to 72% and 93% of baseline in the LVPE and HVPE, respectively. Furthermore, pO 2 in the LVPE group increased highest among the groups. Plasma viscosity in the HVPE group was significantly higher than that in control and LVPE groups. The expression of eNOS in the HVPE group showed higher intensity compared to other groups, especially compared with the control group. Conclusion: Our results demonstrated that cardiac eNOS has responded to plasma viscosity modulation with HVPE and LVPE. This particularly supports the previous studies that revealed the positive effects on cardiac function in animals hemodiluted with HVPE.

An Update on Cardiac Transplantation in the United States.

Science.gov (United States)

Everly, Matthew J

2014-01-01

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

Study of High Sensitive-CRP and Cardiac Marker Enzymes in Acute Coronary Syndrome

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Srikrishna R,

2015-04-01

Full Text Available Background: Inflammation has been proposed as a contributor to different stages in the pathogenesis of Coronary Heart Disease (CHD. High sensitive C-Reactive Protein (hs-CRP, an acute-phase plasma protein synthesized by the liver, is the most extensively studied systemic marker of inflammation. Elevated hsCRP concentrations early in Acute Coronary Syndrome (ACS, prior to the tissue necrosis, may be a surrogate marker for cardiovascular co-morbidities. The cardiac marker enzymes Creatine Kinase myocardial bound (CK-MB, Aspartate Aminotransferase (AST and lactate dehydrogenase (LDH have been known to be increased in coronary artery diseases. Objective: The aim of the study was to measure hs-CRP levels and other cardiac marker enzymes in ACS patients and to compare the levels of hs-CRP with other cardiac marker enzymes between ST Elevation Myocardial Infarction (STEMI and Non-ST Elevation Myocardial Infarction (NSTEMI patients. Material and Methods: The study group consisted of 207 consecutive patients admitted to Sri Siddhartha Medical College Hospital within the first 6 hours from the onset of chest pain. Patients were diagnosed as Unstable Angina (UA, (n=84; STEMI (n=63 and NSTEMI (n=60. ACS patients were compared with 211 healthy age and sex matched controls. Hs-CRP, CK-MB, AST and LDH levels were measured by standard methods in both groups at baseline and forcases at 36-48 hours i.e. Peak levels. Results: ACS patients had significantly (p<0.05 higher levels of hs-CRP, CKMB, AST and LDH in comparison to controls at baseline. Hs-CRP, CK-MB, AST and LDH levels were significantly higher in STEMI patients compared to NSTEMI patients (p<0.05 at baseline. There was a significant difference regarding peak hs-CRP levels between the two groups, as STEMI patients had significantly higher peak hs-CRP levels compared to NSTEMI patients (p<0.05. Conclusion: STEMI patients have significantly higher peak hsCRP levels compared to NSTEMI patients. These data

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

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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

Tuberculosis in a renal allograft recipient presenting with intussusception.

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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.

Mucormycosis (zygomycosis) of renal allograft

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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

Cardiac index after acute ST-segment elevation myocardial infarction measured with phase-contrast cardiac magnetic resonance imaging

International Nuclear Information System (INIS)

Klug, Gert; Reinstadler, Sebastian Johannes; Feistritzer, Hans-Josef; Schwaiger, Johannes P.; Reindl, Martin; Mair, Johannes; Mueller, Silvana; Franz, Wolfgang-Michael; Metzler, Bernhard; Kremser, Christian; Mayr, Agnes

2016-01-01

Phase-contrast CMR (PC-CMR) might provide a fast and robust non-invasive determination of left ventricular function in patients after ST-segment elevation myocardial infarction (STEMI). Cine sequences in the left-ventricular (LV) short-axis and free-breathing, retrospectively gated PC-CMR were performed in 90 patients with first acute STEMI and 15 healthy volunteers. Inter- and intra-observer agreement was determined. The correlations of clinical variables age, gender, ejection fraction, NT pro-brain natriuretic peptide [NT-proBNP] with cardiac index (CI) were calculated. For CI, there was a strong agreement of cine CMR with PC-CMR in healthy volunteers (r: 0.82, mean difference: -0.14 l/min/m 2 , error ± 23 %). Agreement was lower in STEMI patients (r: 0.61, mean difference: -0.17 l/min/m 2 , error ± 32 %). In STEMI patients, CI measured with PC-CMR showed lower intra-observer (1 % vs. 9 %) and similar inter-observer variability (9 % vs. 12 %) compared to cine CMR. CI was significantly correlated with age, ejection fraction and NT-proBNP values in STEMI patients. The agreement of PC-CMR and cine CMR for the determination of CI is lower in STEMI patients than in healthy volunteers. After acute STEMI, CI measured with PC-CMR decreases with age, LV ejection fraction and higher NT-proBNP. (orig.)

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

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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

Metabolomic Profiling in Individuals with a Failing Kidney Allograft.

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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.

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.

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

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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

Effect of emergency PCI combined with rh-BNP therapy on neuroendocrine indicators and cardiac function in patients with acute anterior myocardial infarction

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Yang Ji

2016-06-01

Full Text Available Objective: To analyze the effect of emergency PCI combined with rh-BNP therapy on neuroendocrine indicators and cardiac function in patients with acute anterior myocardial infarction. Methods: A total of 70 cases with acute anterior myocardial infarction who received emergency rescue in our hospital from February 2012 to September 2014 were included for study, and all included patients were divided into control group 38 cases who received emergency PCI treatment alone and observation group 32 cases who received emergency PCI combined with rh-BNP therapy. Differences in the values of neuroendocrine indicators, ventricular collagen remodeling-related indicators, cardiac function indicators, myocardial injury-related indicators and so on were compared between two groups after treatment. Results: Serum ET, PRA, ALD, AngII, NE and E values of observation group after treatment were significantly lower than those of control group (P<0.05; serum PⅠCP and PCⅢ values of observation group after treatment were lower than those of control group, and PⅠCP/ PCⅢ and TIMP-1 values were significantly higher than those of control group (P<0.05; examination of cardiac function by color Doppler ultrasound showed that LAD, LVEDD, LVESD, LVESV and LVEDV values of observation group were lower than those of control group, and LVEF and LVFS values were significantly higher than those of control group (P<0.05; serum CD14++CD2L+, hs-cTnT, HBDH and H-FABP values of observation group after treatment were significantly lower than those of control group, and CD14+CD2L- value was significantly higher than that of control group (P<0.05. Conclusions: Emergency PCI combined with rh-BNP therapy for patients with acute anterior myocardial infarction can significantly improve cardiac function and inhibit ventricular remodeling, and it has positive clinical significance.

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

Dipyridamole-thallium-201 scintigraphy in the prediction of future cardiac events after acute myocardial infarction

International Nuclear Information System (INIS)

Leppo, J.A.; O'Brien, J.; Rothendler, J.A.; Getchell, J.D.; Lee, V.W.

1984-01-01

To evaluate the safety and usefulness of serial thallium scanning immediately after intravenous dipyridamole, we studied 51 patients recovering from acute myocardial infarction. Eight patients experienced angina during the procedure, but there were no serious complications. Patients were followed for a mean period of 19 months after hospital discharge. Eleven of 12 patients who died during follow-up or had another infarction had shown transient defects (redistribution) on their predischarge scan, as had 22 of the 24 patients who needed readmission for management of angina. Among all the other clinical or scintigraphic criteria tested, the presence of redistribution on the dipyridamole-thallium scan was the only significant predictor of these serious cardiac events. Twenty-six patients were also given a submaximal exercise test before discharge, of whom 13 subsequently had serious cardiac events. The exercise test had been positive in only 6 of these 13 patients, whereas the dipyridamole-thallium scan had shown a redistribution pattern in 12 (P less than 0.001). We conclude from this preliminary study that dipyridamole-thallium scintigraphy after myocardial infraction is relatively safe. It appears to be a more sensitive predictor of subsequent cardiac events than a submaximal exercise test and may therefore prove useful in evaluating patients after recovery from a myocardial infarction

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

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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.

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

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

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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.

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

A forgotten approach after cardiac arrest due to acute myocardial ınfarction: Neuroprotective therapeutic hypothermia

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Abdullah Özçelik

2018-02-01

Full Text Available In patients with spontaneous circulation after cardiopulmonary resuscitation, therapeutic hypothermia is defined as the reduction of body temperature to 32-34 ° C within the first 4-6 hours for neuroprotective purposes and to be maintained at this level for 12-24 hours after reaching the target temperature. Therapeutic hypothermia has been practiced since the 1940s. The aim of therapeutic hypothermia is to reduce cerebral edema, convulsive activity, metabolic demand and associated complications by providing low body heat. Therapeutic hypothermia is applied to increase life expectancy and quality of life. In out-of-hospital cardiac arrest, should be performed in comatose patients where initial rhythm is ventricular fibrillation and spontaneous circulation is returned. Herein, we present a 44 years old patient who had an aborted sudden cardiac death due to acute myocardial infarction and performing cardiopulmonary resuscitation for 30 minutes and discharged after 6 days with a successful therapeutic hypothermia.

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

Characterization of Skin Allograft Use in Thermal Injury

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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

Assessment of acute myocarditis by cardiac magnetic resonance imaging: Comparison of qualitative and quantitative analysis methods.

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Imbriaco, Massimo; Nappi, Carmela; Puglia, Marta; De Giorgi, Marco; Dell'Aversana, Serena; Cuocolo, Renato; Ponsiglione, Andrea; De Giorgi, Igino; Polito, Maria Vincenza; Klain, Michele; Piscione, Federico; Pace, Leonardo; Cuocolo, Alberto

2017-10-26

To compare cardiac magnetic resonance (CMR) qualitative and quantitative analysis methods for the noninvasive assessment of myocardial inflammation in patients with suspected acute myocarditis (AM). A total of 61 patients with suspected AM underwent coronary angiography and CMR. Qualitative analysis was performed applying Lake-Louise Criteria (LLC), followed by quantitative analysis based on the evaluation of edema ratio (ER) and global relative enhancement (RE). Diagnostic performance was assessed for each method by measuring the area under the curves (AUC) of the receiver operating characteristic analyses. The final diagnosis of AM was based on symptoms and signs suggestive of cardiac disease, evidence of myocardial injury as defined by electrocardiogram changes, elevated troponin I, exclusion of coronary artery disease by coronary angiography, and clinical and echocardiographic follow-up at 3 months after admission to the chest pain unit. In all patients, coronary angiography did not show significant coronary artery stenosis. Troponin I levels and creatine kinase were higher in patients with AM compared to those without (both P quantitative (ER 0.89 and global RE 0.80) analyses were also similar. Qualitative and quantitative CMR analysis methods show similar diagnostic accuracy for the diagnosis of AM. These findings suggest that a simplified approach using a shortened CMR protocol including only T2-weighted STIR sequences might be useful to rule out AM in patients with acute coronary syndrome and normal coronary angiography.

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

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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.

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.

The use of echocardiography in acute cardiovascular care

DEFF Research Database (Denmark)

Lancellotti, Patrizio; Price, Susanna; Edvardsen, Thor

2014-01-01

Echocardiography is one of the most powerful diagnostic and monitoring tools available to the modern emergency/critical care practitioner. Currently, there is a lack of specific European Association of Cardiovascular Imaging/Acute Cardiovascular Care Association recommendations for the use...... of echocardiography in acute cardiovascular care. In this document, we describe the practical applications of echocardiography in patients with acute cardiac conditions, in particular with acute chest pain, acute heart failure, suspected cardiac tamponade, complications of myocardial infarction, acute valvular heart...

The use of echocardiography in acute cardiovascular care

DEFF Research Database (Denmark)

Lancellotti, Patrizio; Price, Susanna; Edvardsen, Thor

2015-01-01

Echocardiography is one of the most powerful diagnostic and monitoring tools available to the modern emergency/ critical care practitioner. Currently, there is a lack of specific European Association of Cardiovascular Imaging/Acute Cardiovascular Care Association recommendations for the use...... of echocardiography in acute cardiovascular care. In this document, we describe the practical applications of echocardiography in patients with acute cardiac conditions, in particular with acute chest pain, acute heart failure, suspected cardiac tamponade, complications of myocardial infarction, acute valvular heart...

The use of echocardiography in acute cardiovascular care

DEFF Research Database (Denmark)

Lancellotti, Patrizio; Price, Susanna; Edvardsen, Thor

2015-01-01

Echocardiography is one of the most powerful diagnostic and monitoring tools available to the modern emergency/critical care practitioner. Currently, there is a lack of specific European Association of Cardiovascular Imaging/Acute Cardiovascular Care Association recommendations for the use...... of echocardiography in acute cardiovascular care. In this document, we describe the practical applications of echocardiography in patients with acute cardiac conditions, in particular with acute chest pain, acute heart failure, suspected cardiac tamponade, complications of myocardial infarction, acute valvular heart...

Usefulness and limitations of transthoracic echocardiography in heart transplantation recipients

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Galderisi Maurizio

2008-01-01

Full Text Available Abstract Transthoracic echocardiography is a primary non-invasive modality for investigation of heart transplant recipients. It is a versatile tool which provides comprehensive information about cardiac structure and function. Echocardiographic examinations can be easily performed at the bedside and serially repeated without any patient's discomfort. This review highlights the usefulness of Doppler echocardiography in the assessment of left ventricular and right ventricular systolic and diastolic function, of left ventricular mass, valvular heart disease, pulmonary arterial hypertension and pericardial effusion in heart transplant recipients. The main experiences performed by either standard Doppler echocardiography and new high-tech ultrasound technologies are summarised, pointing out advantages and limitations of the described techniques in diagnosing acute allograft rejection and cardiac graft vasculopathy. Despite the sustained efforts of echocardiographic technique in predicting the biopsy state, endocardial myocardial biopsies are still regarded as the gold standard for detection of acute allograft rejection. Conversely, stress echocardiography is able to identify accurately cardiac graft vasculopathy and has a recognised prognostic in this clinical setting. A normal stress-echo justifies postponement of invasive studies. Another use of transthoracic echocardiography is the monitorisation and the visualisation of the catheter during the performance of endomyocardial biopsy. Bedside stress echocardiography is even useful to select appropriately heart donors with brain death. The ultrasound monitoring is simple and effective for monitoring a safe performance of biopsy procedures.

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.

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.

Influence of cardiac decentralization on cardioprotection.

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John G Kingma

Full Text Available The role of cardiac nerves on development of myocardial tissue injury after acute coronary occlusion remains controversial. We investigated whether acute cardiac decentralization (surgical modulates coronary flow reserve and myocardial protection in preconditioned dogs subject to ischemia-reperfusion. Experiments were conducted on four groups of anesthetised, open-chest dogs (n = 32: 1- controls (CTR, intact cardiac nerves, 2- ischemic preconditioning (PC; 4 cycles of 5-min IR, 3- cardiac decentralization (CD and 4- CD+PC; all dogs underwent 60-min coronary occlusion and 180-min reperfusion. Coronary blood flow and reactive hyperemic responses were assessed using a blood volume flow probe. Infarct size (tetrazolium staining was related to anatomic area at risk and coronary collateral blood flow (microspheres in the anatomic area at risk. Post-ischemic reactive hyperemia and repayment-to-debt ratio responses were significantly reduced for all experimental groups; however, arterial perfusion pressure was not affected. Infarct size was reduced in CD dogs (18.6 ± 4.3; p = 0.001, data are mean ± 1 SD compared to 25.2 ± 5.5% in CTR dogs and was less in PC dogs as expected (13.5 ± 3.2 vs. 25.2 ± 5.5%; p = 0.001; after acute CD, PC protection was conserved (11.6 ± 3.4 vs. 18.6 ± 4.3%; p = 0.02. In conclusion, our findings provide strong evidence that myocardial protection against ischemic injury can be preserved independent of extrinsic cardiac nerve inputs.

Albumin administration is associated with acute kidney injury in cardiac surgery: a propensity score analysis.

Science.gov (United States)

Frenette, Anne Julie; Bouchard, Josée; Bernier, Pascaline; Charbonneau, Annie; Nguyen, Long Thanh; Rioux, Jean-Philippe; Troyanov, Stéphan; Williamson, David R

2014-11-14

The risk of acute kidney injury (AKI) with the use of albumin-containing fluids compared to starches in the surgical intensive care setting remains uncertain. We evaluated the adjusted risk of AKI associated with colloids following cardiac surgery. We performed a retrospective cohort study of patients undergoing on-pump cardiac surgery in a tertiary care center from 2008 to 2010. We assessed crystalloid and colloid administration until 36 hours after surgery. AKI was defined by the RIFLE (risk, injury, failure, loss and end-stage kidney disease) risk and Acute Kidney Injury Network (AKIN) stage 1 serum creatinine criterion within 96 hours after surgery. Our cohort included 984 patients with a baseline glomerular filtration rate of 72 ± 19 ml/min/1.73 m(2). Twenty-three percent had a reduced left ventricular ejection fraction (LVEF), thirty-one percent were diabetics and twenty-three percent underwent heart valve surgery. The incidence of AKI was 5.3% based on RIFLE risk and 12.0% based on the AKIN criterion. AKI was associated with a reduced LVEF, diuretic use, anemia, heart valve surgery, duration of extracorporeal circulation, hemodynamic instability and the use of albumin, pentastarch 10% and transfusions. There was an important dose-dependent AKI risk associated with the administration of albumin, which also paralleled a higher prevalence of concomitant risk factors for AKI. To address any indication bias, we derived a propensity score predicting the likelihood to receive albumin and matched 141 cases to 141 controls with a similar risk profile. In this analysis, albumin was associated with an increased AKI risk (RIFLE risk: 12% versus 5%, P = 0.03; AKIN stage 1: 28% versus 13%, P = 0.002). We repeated this methodology in patients without postoperative hemodynamic instability and still identified an association between the use of albumin and AKI. Albumin administration was associated with a dose-dependent risk of AKI and remained significant using a propensity

Relationship between Cardiac Troponin and Thrombo-Inflammatory Molecules in Prediction of Outcome after Acute Ischemic Stroke

DEFF Research Database (Denmark)

Csecsei, Peter; Pusch, Gabriella; Ezer, Erzsebet

2018-01-01

BACKGROUND: In patients with acute ischemic stroke (AIS) without cardiovascular complications, we investigated the association of serum concentration of cardiac troponin (high-sensitivity cardiac troponin T [hs-cTnT]) with thrombo-inflammatory markers. METHODS: Thirty-five patients with first......-ever AIS were prospectively examined. Serum hs-cTnT was measured 6 and 24 hours after stroke, whereas S100B, high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand, tissue plasminogen activator (tPA), monocyte chemoattractant protein-1 (MCP-1), and P-selectin were measured 6 and 72 hours after...... stroke. Severity of stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS) on admission, 24 hours later, and at discharge. RESULTS: Concentration of MCP-1 at 6 hours was higher in the serum of patients with worsened NIHSS by 24 hours (P = .009). Concentration of hs-cTnT at both 6...

Meniscal allograft transplantation: a meta-analysis

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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

Association of elevated serum cardiac troponin-I level and complications in acute heart failurecases

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Farjana Akhter

2013-07-01

Full Text Available Acute heart failure is one of the major causes of morbidity and mortality all over the world. Available published data has suggested that patients of acute heart failure with elevated level of serum cardiac troponin-I (cTn-I have more adverse outcomes than that of acute heart failure with normal cTn-I level. Elevated level of serum cTn-I is a potential risk factor for acute heart failure. This study was carried out in the department of Biochemistry, Dhaka Medical College and National Institute of Cardiovascular Disease (NICVD during the period from January 2010 to December 2010. In this study, 100 patients with acute heart failure were enrolled. Out of 100 cases, 50 had elevated serum cTn-I (cTn-I ³ 1.0 ng/ml and 50 had normal serum cTn-I (cTn-I < 1.0 ng/ml. The adverse outcome of the two groups were recorded and compared. Patients with high and normal serum cTn-I had mean age of 52.40 ± 8.10 years and 54.64 ± 7.26 years respectively while male and female cases were equally distributed. Left ventricular systolic dysfunction (lower ejection fraction was significantly (p<0.05 higher among cases with elevated cTn-I level compared to those with normal level. The rate of renal failure (raised serum creatinine, impaired liver functions (raised ALT and AST and abnormal serum electrolytes were significantly higher among the patients with elevated cTn-I compared to those with normal level. The study showed that elevated serum cTn-I level was a good biomarker to indicate adverse complications in acute heart failure cases. Ibrahim Med. Coll. J. 2013; 7(2: 32-34

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.

Coronary computed tomography and triple rule out CT in patients with acute chest pain and an intermediate cardiac risk profile. Part 1: Impact on patient management

International Nuclear Information System (INIS)

Gruettner, Joachim; Fink, Christian; Walter, Thomas; Meyer, Mathias; Apfaltrer, Paul; Schoepf, U. Joseph; Saur, Joachim; Sueselbeck, Tim; Traunwieser, Dominik; Takx, Richard

2013-01-01

Objective: To evaluate the impact of coronary CT angiography (coronary CTA) or “triple-rule-out” CT angiography (TRO-CTA) on patient management in the work-up of patients with acute chest pain and an intermediate cardiac risk profile. Materials and methods: 100 patients with acute chest pain and an intermediate cardiac risk for acute coronary syndrome (ACS) underwent coronary CTA or TRO-CTA for the evaluation of chest pain. Patients with a high and low cardiac risk profile were not included in this study. All patients with significant coronary stenosis >50% on coronary CTA underwent invasive coronary catheterization (ICC). Important other pathological findings were recorded. All patients had a 90-day follow-up period for major adverse cardiac events (MACE). Results: Based on a negative coronary CTA 60 of 100 patients were discharged on the same day. None of the discharged patients showed MACE during the 90-day follow-up. Coronary CTA revealed a coronary stenosis >50% in 19 of 100 patients. ICC confirmed significant coronary stenosis in 17/19 patients. Among the 17 true positive patients, 9 underwent percutaneous coronary intervention with stent implantation, 7 were received intensified medical therapy, and 1 patient underwent coronary artery bypass surgery. A TRO-CTA protocol was performed in 36/100 patients due to elevated D-dimer levels. Pulmonary embolism was present in 5 patients, pleural effusion of unknown etiology in 3 patients, severe right ventricular dysfunction with pericardial effusion in 1 patient, and an incidental bronchial carcinoma was diagnosed in 1 patient. Conclusion: Coronary CTA and TRO-CTA allow a rapid and safe discharge in the majority of patients presenting with acute chest pain and an intermediate risk for ACS while at the same time identifies those with significant coronary artery stenosis

Coronary computed tomography and triple rule out CT in patients with acute chest pain and an intermediate cardiac risk profile. Part 1: Impact on patient management

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Gruettner, Joachim, E-mail: joachim.gruettner@umm.de [Emergency Department, University Medical Center, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Fink, Christian, E-mail: Christian.Fink@umm.de [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center, Medical Faculty Mannheim, Heidelberg University, Mannheim (Germany); Walter, Thomas, E-mail: thomas.walter@umm.de [Emergency Department, University Medical Center, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Meyer, Mathias, E-mail: mr.meyer.mathias@gmail.com [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center, Medical Faculty Mannheim, Heidelberg University, Mannheim (Germany); Apfaltrer, Paul, E-mail: Paul.Apfaltrer@umm.de [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center, Medical Faculty Mannheim, Heidelberg University, Mannheim (Germany); Schoepf, U. Joseph, E-mail: schoepf@musc.edu [Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, Ashley River Tower, 25 Courtenay Drive, Charleston, SC 29425-2260 (United States); Saur, Joachim, E-mail: joachim.saur@umm.de [1st Department of Medicine (Cardiology), University Medical Center, Medical Faculty Mannheim, Heidelberg University, Mannheim (Germany); Sueselbeck, Tim, E-mail: tim.sueselbeck@umm.de [1st Department of Medicine (Cardiology), University Medical Center, Medical Faculty Mannheim, Heidelberg University, Mannheim (Germany); Traunwieser, Dominik, E-mail: dominik.traunwieser@umm.de [1st Department of Medicine (Cardiology), University Medical Center, Medical Faculty Mannheim, Heidelberg University, Mannheim (Germany); Takx, Richard, E-mail: richard.takx@gmail.com [Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, Ashley River Tower, 25 Courtenay Drive, Charleston, SC 29425-2260 (United States); and others

2013-01-15

Objective: To evaluate the impact of coronary CT angiography (coronary CTA) or “triple-rule-out” CT angiography (TRO-CTA) on patient management in the work-up of patients with acute chest pain and an intermediate cardiac risk profile. Materials and methods: 100 patients with acute chest pain and an intermediate cardiac risk for acute coronary syndrome (ACS) underwent coronary CTA or TRO-CTA for the evaluation of chest pain. Patients with a high and low cardiac risk profile were not included in this study. All patients with significant coronary stenosis >50% on coronary CTA underwent invasive coronary catheterization (ICC). Important other pathological findings were recorded. All patients had a 90-day follow-up period for major adverse cardiac events (MACE). Results: Based on a negative coronary CTA 60 of 100 patients were discharged on the same day. None of the discharged patients showed MACE during the 90-day follow-up. Coronary CTA revealed a coronary stenosis >50% in 19 of 100 patients. ICC confirmed significant coronary stenosis in 17/19 patients. Among the 17 true positive patients, 9 underwent percutaneous coronary intervention with stent implantation, 7 were received intensified medical therapy, and 1 patient underwent coronary artery bypass surgery. A TRO-CTA protocol was performed in 36/100 patients due to elevated D-dimer levels. Pulmonary embolism was present in 5 patients, pleural effusion of unknown etiology in 3 patients, severe right ventricular dysfunction with pericardial effusion in 1 patient, and an incidental bronchial carcinoma was diagnosed in 1 patient. Conclusion: Coronary CTA and TRO-CTA allow a rapid and safe discharge in the majority of patients presenting with acute chest pain and an intermediate risk for ACS while at the same time identifies those with significant coronary artery stenosis.

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.

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.

Diagnosis of acute myocardial infarction in patients undergoing open heart surgery: a comparison of serial myocardial imaging with cardiac enzymes, electrocardiography, and vectocardiography

International Nuclear Information System (INIS)

Lowenthal, I.S.; Parisi, A.F.; Tow, D.E.; Barsamian, E.M.; Sasahara, A.A.; McCaughan, D.; Clemson, H.C.

1977-01-01

In 44 consecutive patients undergoing elective open heart surgery (OHS), serial electrocardiograms (ECG), vectorcardiograms (VCG), serum CPK, cardiac isoenzymes (CPKMB), and myocardial images using Tc-99m pyrophosphate were obtained, before and after the operation, for the detection of acute myocardial infarction (AMI). Twenty-nine patients developed one or more positive tests postoperatively. Two patients had positive myocardial scintiscans; both had other evidence of infarction. Conversely, the appearance of CPKMB, or new ECG and VCG changes, occurred frequently without evidence of infarction, and were not associated with the development of a positive scintiscan. The results show that false-negative results are infrequent in patients imaged early after OHS, and that cardiac surgical procedures do not cause a high incidence of false-positive scintigrams. Consequently, radionuclide imaging for AMI offers an important adjunct for excluding acute infarction following open heart surgery

Acute effects of firefighting on cardiac performance.

Science.gov (United States)

Fernhall, Bo; Fahs, Christopher A; Horn, Gavin; Rowland, Thomas; Smith, Denise

2012-02-01

This study examined standard echocardiographic measures of cardiac size and performance in response to a 3-h firefighting training exercise. Forty experienced male personnel completed a standardized 3 h live firefighting exercise. Before and after the firefighting activities, participants were weighed, height, heart rate, blood pressure and blood samples were obtained, and echocardiographic measurements were made. Firefighting produced significant decreases in left ventricular diastolic dimension, stroke volume, fractional shortening, and mitral E velocity, tachycardia, a rise in core temperature, and a reduction in calculated plasma volume. On tissue Doppler imaging, there were no changes in systolic contractile function, but a decreased lateral wall diastolic velocity was observed. These findings show that 3 h of live firefighting produced cardiac changes consistent with cardiac fatigue, coupled with a decrease in systemic arterial compliance. These data show that live firefighting produces significant cardiovascular changes and future work is needed to evaluate if these changes are related to the increase in cardiovascular risk during live firefighting.

Chondroblastoma of the Knee Treated with Resection and Osteochondral Allograft Reconstruction

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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.

Pretransplant Immune- and Apoptosis-Related Gene Expression Is Associated with Kidney Allograft Function

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Dorota Kamińska

2016-01-01

Full Text Available Renal transplant candidates present immune dysregulation, caused by chronic uremia. The aim of the study was to investigate whether pretransplant peripheral blood gene expression of immune factors affects clinical outcome of renal allograft recipients. Methods. In a prospective study, we analyzed pretransplant peripheral blood gene expression in87 renal transplant candidates with real-time PCR on custom-designed low density arrays (TaqMan. Results. Immediate posttransplant graft function (14-day GFR was influenced negatively by TGFB1 (P=0.039 and positively by IL-2 gene expression (P=0.040. Pretransplant blood mRNA expression of apoptosis-related genes (CASP3, FAS, and IL-18 and Th1-derived cytokine gene IFNG correlated positively with short- (6-month GFR CASP3: P=0.027, FAS: P=0.021, and IFNG: P=0.029 and long-term graft function (24-month GFR CASP3: P=0.003, FAS: P=0.033, IL-18: P=0.044, and IFNG: P=0.04. Conclusion. Lowered pretransplant Th1-derived cytokine and apoptosis-related gene expressions were a hallmark of subsequent worse kidney function but not of acute rejection rate. The pretransplant IFNG and CASP3 and FAS and IL-18 genes’ expression in the recipients’ peripheral blood is the possible candidate for novel biomarker of short- and long-term allograft function.

The role of CD8+ T cells during allograft rejection

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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.

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.

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

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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.

Noninvasive diagnosis of allograft vascular disease after heart transplantation

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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.

A fatal case of acute pulmonary embolism caused by right ventricular masses of acute lymphoblastic lymphoma-leukemia in a 13 year old girl

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Yu Mi Ko Ko

2012-07-01

Full Text Available We report a case of a 13-year-old girl with acute lymphoblastic lymphoma- leukemia, who presented with a cardiac metastasis in the right ventricle, resulting in a pulmonary embolism. At the time of her leukemia diagnosis, a cardiac mass was incidentally found. The differential diagnosis for this unusual cardiac mass included cardiac tumor, metastasis, vegetation, and thrombus. Empirical treatment was initiated, including anticoagulation and antibiotics. She underwent plasmapheresis and was administered oral prednisolone for her leukemia. Five days later, she experienced sudden hemodynamic collapse and required extracorporeal membrane oxygenation insertion and emergency surgery. These interventions proved futile, and the patient died. Pathology revealed that the cardiac mass comprised an aggregation of small, round, necrotic cells consistent with leukemia. This is the first known case of acute lymphoblastic leukemia presenting as a right ventricular mass, with consequent fatal acute pulmonary embolism. A cardiac mass in a child with acute leukemia merits investigation to rule out every possible etiology, including vegetation, thrombus, and even a mass of leukemic cells, which could result in the fatal complication of pulmonary embolism.

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

Use of bone allograft in Kuala Lumpur Hospital

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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

Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition

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Fabiansen, Christian; Lykke, Mikkel; Hother, Anne-Louise

2015-01-01

BACKGROUND: Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. OBJECTIVE: To determine malnutrition-induced echocardiographic disturbances...... and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. METHODS AND RESULTS: Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet...... groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (pMalnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide...

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.)

One-stage human acellular nerve allograft reconstruction for digital nerve defects

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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.

The Unpredictable Effect of Changing Cardiac Output on Hypoxemia after Acute Pulmonary Thromboembolism

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John Y. C. Tsang

2008-01-01

Full Text Available Previous studies reported that the degree of hypoxemia following acute pulmonary thromboembolism (APTE was highly variable and that its mechanism was mainly due to the creation of many high and low ventilation/perfusion (V/Q units, as a result of the heterogeneous regional blood flow (Q caused by embolic obstruction. We studied the effect of changing cardiac output (Q t on gas exchange after APTE in 5 embolized piglets (23 ± 3 Kg, using Dobutamine intermittently at approximately 20 μg/kg/min for 120 minutes. The distribution of ventilation (V and perfusion (Q at various times was mapped using fluorescent microspheres in 941 ± 60 lung regions. After APTE, increase in Q t by Dobutamine improved venous oxygen tension (PvO 2 but arterial PaO 2 did not change consistently. On the other hand, cluster analysis showed that the V/Q ratio of most lung regions was lowered due to increases in Q at the same time. We concluded that the effect of changing cardiac output on gas exchange following APTE was affected by the simultaneous and varying balance between the changing V/Q mismatch and the concomitantly changing PvO 2 , which might explain the unpredictability of PaO 2 in the clinical setting.

Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects.

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David Ojeda

Full Text Available Although the therapeutic effects of Vagus Nerve Stimulation (VNS have been recognized in pre-clinical and pilot clinical studies, the effect of different stimulation configurations on the cardiovascular response is still an open question, especially in the case of VNS delivered synchronously with cardiac activity. In this paper, we propose a formal mathematical methodology to analyze the acute cardiac response to different VNS configurations, jointly considering the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube sampling method was chosen to design a uniform experimental plan, composed of 75 different VNS configurations, with different values for the main parameters (current amplitude, number of delivered pulses, pulse width, interpulse period and the delay between the detected cardiac event and VNS onset. These VNS configurations were applied to 6 healthy, anesthetized sheep, while acquiring the associated cardiovascular response. Unobserved VNS configurations were estimated using a Gaussian process regression (GPR model. In order to quantitatively analyze the effect of each parameter and their combinations on the cardiac response, the Sobol sensitivity method was applied to the obtained GPR model and inter-individual sensitivity markers were estimated using a bootstrap approach. Results highlight the dominant effect of pulse current, pulse width and number of pulses, which explain respectively 49.4%, 19.7% and 6.0% of the mean global cardiovascular variability provoked by VNS. More interestingly, results also quantify the effect of the interactions between VNS parameters. In particular, the interactions between current and pulse width provoke higher cardiac effects than the changes on the number of pulses alone (between 6 and 25% of the variability. Although the sensitivity of individual VNS parameters seems similar for chronotropic, dromotropic and inotropic responses, the interacting effects of VNS parameters

Evaluation of allograft perfusion by radionuclide first-pass study in renal failure following renal transplantation

International Nuclear Information System (INIS)

Baillet, G.; Ballarin, J.; Urdaneta, N.; Campos, H.; Vernejoul, P. de; Fermanian, J.; Kellershohn, C.; Kreis, H.

1986-01-01

To assess the diagnostic value of indices measured on a first-pass curve, we performed 72 radionuclide renal first-pass studies (RFP) in 21 patients during the early weeks following renal allograft transplantation. The diagnosis was based on standard clinical and biochemical data and on fine needle aspiration biopsy (FNAB) of the transplant. Aortic and renal first-pass curves were filtered using a true low-pass filter and five different indices of renal perfusion were computed, using formulae from the literature. Statistical analysis performed on the aortic and renal indices indicated excellent reproducibility of the isotopic study. Although renal indices presented a rather large scatter, they all discriminated well between normal and rejection. Three indices have a particularly good diagnostic value. In the discrimination between rejection and Acute Tubular Necrosis (ATN), only one index gave satisfying results. The indices, however, indicate that there are probably ATN with an alternation of renal perfusion and rejection episodes where perfusion is almost intact. We conclude that radionuclide first-pass study allows accurate and reproducible quantitation of renal allograft perfusion. The measured parameters are helpful to follow up the course of a post-transplantation renal failure episode and to gain more insight into renal ischemia following transplantation. (orig.)

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)

Nitrates for the prevention of cardiac morbidity and mortality in patients undergoing non-cardiac surgery.

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Zhao, Na; Xu, Jin; Singh, Balwinder; Yu, Xuerong; Wu, Taixiang; Huang, Yuguang

2016-08-04

Cardiac complications are not uncommon in patients undergoing non-cardiac surgery, especially in patients with coronary artery disease (CAD) or at high risk of CAD. Perioperative cardiac complications can lead to mortality and morbidity, as well as higher costs for patient care. Nitrates, which are among the most commonly used cardiovascular drugs, perform the function of decreasing cardiac preload while improving cardiac blood perfusion. Sometimes, nitrates are administered to patients undergoing non-cardiac surgery to reduce the incidence of cardiac complications, especially for patients with CAD. However, their effects on patients' relevant outcomes remain controversial. • To assess effects of nitrates as compared with other interventions or placebo in reducing cardiac risk (such as death caused by cardiac factors, angina pectoris, acute myocardial infarction, acute heart failure and cardiac arrhythmia) in patients undergoing non-cardiac surgery.• To identify the influence of different routes and dosages of nitrates on patient outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Chinese BioMedical Database until June 2014. We also searched relevant conference abstracts of important anaesthesiology or cardiology scientific meetings, the database of ongoing trials and Google Scholar.We reran the search in January 2016. We added three potential new studies of interest to the list of 'Studies awaiting classification' and will incorporate them into our formal review findings for the review update. We included randomized controlled trials (RCTs) comparing nitrates versus no treatment, placebo or other pharmacological interventions in participants (15 years of age and older) undergoing non-cardiac surgery under any type of anaesthesia. We used standard methodological procedures as expected by Cochrane. Two review authors selected trials, extracted data from included studies and assessed risk of bias. We

Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

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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.

DOPAMINE EFFECT ON CARDIAC REMODELING IN EXPERIMENT

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V. R. Veber

2009-01-01

Full Text Available Aim. To study morphologic changes in myocardium of Wistar rats caused by single and long term dopamine administration.Methods. In acute study dopamine 10 mkg/kg was administrated to 15 rats by a single intraperitoneal injection. The material was taken in 2, 6, 24 hours and in 1 month after drug administration. In chronic study dopamine 10 mkg/kg was administrated to 15 rats 3 times a day by intraperitoneal injections during 2 weeks. The material was taken just after the drug administration was stopped and in 1 month of animals keeping without stress and drug influences. Control group included 15 rats comparable with experimental animals in age and weight. They were keeped without stress and drug influences. Morphometric parameters of left and right ventricles were evaluated as well as density of cardiomyocytes, collagen, vessels and volume of extracellular space.Results. The enlargement of cardiac fibrosis is found both in acute, and in chronic study. In acute study cardiac fibrosis was located mainly in a right ventricle. In chronic study cardiac fibrosis was located in both ventricles, but also mainly in a right one.Conclusion. Significant morphological «asynchronism» of the left and right ventricles remodeling requires elaboration of methods of myocardium protection and cardiac function control during dopamine administration. 

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

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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.

Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery

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Su Rin Shin

2016-01-01

Full Text Available The incidence of acute kidney injury after cardiac surgery (CS-AKI ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI.

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

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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.

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

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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.

Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

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Stanley Cohan MD, PhD

2015-03-01

Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

Early kidney allograft loss - is there scope for improvement?

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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.

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...

[Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock].

Science.gov (United States)

Sánchez Marteles, Marta; Urrutia, Agustín

2014-03-01

Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index 30 mmHg) and absent or reduced diuresis (acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease. Copyright © 2014 Elsevier España, S.L. All rights reserved.

How is cardiac troponin released from injured myocardium?

DEFF Research Database (Denmark)

Mair, Johannes; Lindahl, Bertil; Hammarsten, Ola

2017-01-01

Cardiac troponin I and cardiac troponin T are nowadays the criterion biomarkers for the laboratory diagnosis of acute myocardial infarction due to their very high sensitivities and specificities for myocardial injury. However, still many aspects of their degradation, tissue release and eliminatio...

Electrocardiographic Findings in Patients With Acute Coronary Syndrome Presenting With Out-of-Hospital Cardiac Arrest.

Science.gov (United States)

Sarak, Bradley; Goodman, Shaun G; Brieger, David; Gale, Chris P; Tan, Nigel S; Budaj, Andrzej; Wong, Graham C; Huynh, Thao; Tan, Mary K; Udell, Jacob A; Bagai, Akshay; Fox, Keith A A; Yan, Andrew T

2018-02-01

We sought to characterize presenting electrocardiographic findings in patients with acute coronary syndromes (ACSs) and out-of-hospital cardiac arrest (OHCA). In the Global Registry of Acute Coronary Events and Canadian ACS Registry I, we examined presenting and 24- to 48-hour follow-up ECGs (electrocardiogram) of ACS patients who survived to hospital admission, stratified by presentation with OHCA. We assessed the prevalence of ST-segment deviation and bundle branch blocks (assessed by an independent ECG core laboratory) and their association with in-hospital and 6-month mortality among those with OHCA. Of the 12,040 ACS patients, 215 (1.8%) survived to hospital admission after OHCA. Those with OHCA had higher presenting rates of ST-segment elevation, ST-segment depression, T-wave inversion, precordial Q-waves, left bundle branch block (LBBB), and right bundle branch block (RBBB) than those without. Among patients with OHCA, those with ST-segment elevation had significantly lower in-hospital mortality (20.9% vs 33.0%, p = 0.044) and a trend toward lower 6-month mortality (27% vs 39%, p = 0.060) compared with those without ST-segment elevation. Conversely, among OCHA patients, LBBB was associated with significantly higher in-hospital and 6-month mortality rates (58% vs 22%, p presenting ECG resolved by 24 to 48 hours. In conclusion, compared with ACS patients without cardiac arrest, those with OHCA had higher rates of ST-segment elevation, LBBB, and RBBB on admission. Among OHCA patients, ST-segment elevation was associated with lower in-hospital mortality, whereas LBBB was associated with higher in-hospital and 6-month mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA).

Science.gov (United States)

Stone, Adam F M; Mendall, Michael A; Kaski, Juan-Carlos; Edger, Tracey M; Risley, Paul; Poloniecki, Jan; Camm, A John; Northfield, Timothy C

2002-09-03

Infection with Helicobacter pylori and Chlamydia pneumoniae is associated with coronary heart disease. We conducted an intervention study using antibiotics against these bacteria in patients with acute coronary syndromes to determine whether antibiotics reduce inflammatory markers and adverse cardiac events. Patients (n=325) admitted with acute myocardial infarction or unstable angina (acute coronary syndromes) were randomized to receive a 1-week course of 1 of 3 treatment regimens: (1) placebo; (2) amoxicillin (500 mg twice daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily); or (3) azithromycin (500 mg once daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily). Serum fibrinogen, white cell count, and high-sensitivity C-reactive protein were measured at study entry and at 1, 3, and 12 months during follow-up. Cardiac death and readmission with acute coronary syndrome were considered clinical end points. Patients were followed for 1 year. C-reactive protein levels were reduced (P=0.03) in unstable angina patients receiving amoxicillin, and fibrinogen was reduced in both patient groups receiving antibiotics (P=0.06). There were 17 cardiac deaths and 71 readmissions with acute coronary syndrome. No difference in frequency or timing of end points was observed between the 2 antibiotic groups. At 12 weeks, there was a 36% reduction in all end points in patients receiving antibiotics compared with placebo (P=0.02). This reduction persisted during the 1-year follow-up. Neither C pneumoniae nor H pylori antibody status was significantly related to response to treatment. Antibiotic treatment significantly reduced adverse cardiac events in patients with acute coronary syndromes, but the effect was independent of H pylori or C pneumoniae seropositivity.

Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides

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Tripti Singh, MD

2017-11-01

Conclusions. Patients with MN have higher incidence of acute rejection after kidney transplant but have similar 10-year allograft survival in comparison to the other glomerular diseases like IgAN, FSGS, and LN.

The significance of parenchymal changes of acute cellular rejection in predicting chronic liver graft rejection

NARCIS (Netherlands)

Gouw, ASH; van den Heuvel, MC; van den Berg, AP; Slooff, NJH; de Jong, KP; Poppema, S

2002-01-01

Background. Chronic rejection (CR) in liver allografts shows a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition

Effects of AL 107, a novel semisynthetic cardiac glycoside, on the cardiovascular system in anaesthetized beagle dogs with pentobarbital-induced cardiac insufficiency

NARCIS (Netherlands)

Kogel, B; Schneider, J; Gleitz, J; Wilffert, B; Peters, Thies

The inotropic efficacy, arrhythmogenicity and cardiohaemodynamic properties of AL 107 (3-alpha-methyl-digitoxigenin glucoside. CAS 62190-59-4), a novel cardiac glycoside, were studied in anaesthetized dogs with pentobarbital-induced acute cardiac insufficiency. Three groups of dogs received AL 107,

Kidney allograft tolerance in diabetic patients after total lymphoid irradiation (TLI)

Energy Technology Data Exchange (ETDEWEB)

Ang, K.K.; Vanrenterighem, Y.; Waer, M.; Michielsen, P.; Schueren, E. van der (University Hospital St. Rafael, Leuven (Belgium)); Vandeputte, M. (Louvain Univ. (Belgium). Rega Institute for Medical Research)

1985-04-01

The value of total lymphoid irradiation (TLI) combined with low dose prednisone as sole immunosuppressive regimen in renal allograft transplantation in humans has been investigated. Seventeen patients with end-stage diabetic nephropathy received TLI to a cumulative dose of 20-30 Gy in fractions of 1 Gy. Cadaver kidneys were grafted as soon as they were available after completion of TLI. Profound and long-term immunosuppression has been achieved in 17 patients. Six patients live already more than one year and 7 for less than one year with a functioning kidney graft. One patient returned to chronic hemodialysis 11 months after transplantation and died of pericardial tamponade one month later. One patient had severe acute rejection for which cyclosporine A was administered; he died of septic shock as a consequence of immune deficiency a month later. The other two patients succumbed to other causes (myocardial infarction and hyperglycemia).

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.

Cardiac Autonomic and Blood Pressure Responses to an Acute Foam Rolling Session.

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Lastova, Kevin; Nordvall, Michael; Walters-Edwards, Michelle; Allnutt, Amy; Wong, Alexei

2018-03-22

Foam Rolling (FR) is a self-myofascial release method that has become extremely popular among athletes and fitness enthusiasts for its ability to improve flexibility and range of motion and alleviate delayed onset muscle soreness. However, the cardiac autonomic modulation and blood pressure (BP) responses induced by an acute FR session are currently unknown. The present study evaluated the effects of an acute session of FR exercise on heart rate variability (HRV) and BP responses in healthy individuals. Fifteen (M=8, F=7) healthy subjects completed either a FR or non-exercise control trial in randomized order. HRV and BP measurements were collected at baseline, 10 and 30 min after each trial. There were significant increases (P < 0.01) in markers of vagal tone (nHF) for 30 min after the FR trial, while no changes from baseline were observed following control. There were also significant decreases (P < 0.05) in markers of sympathetic activity (nLF), sympathovagal balance (nLF/nHF), systolic BP and diastolic BP at 10 and 30 min after the trial KB trial while no changes from baseline were observed after the control trial. Our findings indicate that FR decreases sympathovagal balance for 30 min post-intervention which is concurrent with an important hypotensive effect. Further research is warranted to evaluate the potential cardiovascular protective effects of FR in diverse populations.

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

Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.

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Kazuaki Yamanaka

Full Text Available The association of complement with the progression of acute T cell mediated rejection (ATCMR is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs in acute T-cell mediated rejection using rat and human renal allografts.We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP by immunohistochemical staining in human renal grafts and their clinical course.qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry, was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

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

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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.

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

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...

Early biomarkers of acute kidney failure after heart angiography or heart surgery in patients with acute coronary syndrome or acute heart failure.

Science.gov (United States)

Torregrosa, Isidro; Montoliu, Carmina; Urios, Amparo; Elmlili, Nisrin; Puchades, María Jesús; Solís, Miguel Angel; Sanjuán, Rafael; Blasco, Maria Luisa; Ramos, Carmen; Tomás, Patricia; Ribes, José; Carratalá, Arturo; Juan, Isabel; Miguel, Alfonso

2012-01-01

Acute kidney injury (AKI) is a common complication in cardiac surgery and coronary angiography, which worsens patients' prognosis. The diagnosis is based on the increase in serum creatinine, which is delayed. It is necessary to identify and validate new biomarkers that allow for early and effective interventions. To assess the sensitivity and specificity of neutrophil gelatinase-associated lipocalin in urine (uNGAL), interleukin-18 (IL-18) in urine and cystatin C in serum for the early detection of AKI in patients with acute coronary syndrome or heart failure, and who underwent cardiac surgery or catheterization. The study included 135 patients admitted to the intensive care unit for acute coronary syndrome or heart failure due to coronary or valvular pathology and who underwent coronary angiography or cardiac bypass surgery or valvular replacement. The biomarkers were determined 12 hours after surgery and serum creatinine was monitored during the next six days for the diagnosis of AKI. The area under the ROC curve (AUC) for NGAL was 0.983, and for cystatin C and IL-18 the AUCs were 0.869 and 0.727, respectively. At a cut-off of 31.9 ng/ml for uNGAL the sensitivity was 100% and the specificity was 91%. uNGAL is an early marker of AKI in patients with acute coronary syndrome or heart failure and undergoing cardiac surgery and coronary angiography, with a higher predictive value than cystatin C or IL-18.

Myoglobinaemia in relation to cardiac necrosis

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McComb, J M

1981-01-01

An evaluation of the usefulness of estimation of the serum myoglobin in the detection of myocardial necrosis was made in patients with suspected acute ischemic heart disease and in patients in whom elective cardiac catheterization was performed. Measurement of serum myoglobin, by radioimmunoassay, in patients admitted with suspected acute myocardial infarction, suggested that a raised serum myoglobin level was a sensitive indicator of myocardial necrosis. It also showed that the serum myoglobin rose to abnormal levels before the serum creatine kinase. A study of 70 consecutive patients confirmed that the serum myoglobin level is a sensitive indicator of acute myocardial infarction and showed that its sensitivity was greater, and its specificity similar to that of serum creatine kinase. This study allowed calculation of a predictive index for the diagnosis of acute myocardial infarction from the serum myoglobin and serum creatine kinase six hours after the onset of symptoms. The use of a single myoglobin measurement in 114 patients admitted to a coronary care unit was then studied. The proposition that myocardial damage might results from cardiac catheterization was investigated in 115 patients.

Clinical, Histological, and Molecular Markers Associated With Allograft Loss in Transplant Glomerulopathy Patients.

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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.

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

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Dongxia Ma

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

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

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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.

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

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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.

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

Enduring somatic threat perceptions and post-traumatic stress disorder symptoms in survivors of cardiac events.

Science.gov (United States)

Meli, Laura; Alcántara, Carmela; Sumner, Jennifer A; Swan, Brendan; Chang, Bernard P; Edmondson, Donald

2017-04-01

Post-traumatic stress disorder due to acute cardiovascular events may be uniquely defined by enduring perceptions of somatic threat. We tested whether post-traumatic stress disorder at 1 month post-acute coronary syndrome indeed required both high peritraumatic threat during the acute coronary syndrome and ongoing cardiac threat perceptions. We assessed peritraumatic threat during emergency department enrollment of 284 patients with a provisional acute coronary syndrome diagnosis and cardiac threat perceptions and post-traumatic stress disorder symptoms 1 month post-discharge. In a multiple regression model with adjustment for important covariates, emergency department threat perceptions were associated with higher 1 month post-traumatic stress disorder symptoms only among those with high levels of ongoing cardiac threat.

Effects of low intensity pulsed ultrasound with and without increased cortical porosity on structural bone allograft incorporation

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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

Role of Soluble ST2 as a Marker for Rejection after Heart Transplant.

Science.gov (United States)

Lee, Ga Yeon; Choi, Jin-Oh; Ju, Eun-Seon; Lee, Yoo-Jung; Jeon, Eun-Seok

2016-11-01

Endomyocardial biopsy is obligatory during the first year after heart transplant (HTx) for the surveillance of acute rejection. Previous attempts using cardiac biomarkers for the detection of rejection failed to show enough evidence to substitute endomyocardial biopsy. Therefore, this study sought the possibility of using soluble ST2 (sST2), a novel cardiovascular marker, as a surrogate marker for acute allograft rejection after HTx. A total of 494 blood samples acquired at the time of endomyocardial biopsy were analyzed in 67 HTx cases from September 2006 to August 2014. Significant rejection was defined as International Society of Heart and Lung Transplant (ISHLT) score ≥2R and humoral rejection accompanied by hemodynamic instability. Twenty cases of HTx with 22 blood samples showed significant rejection in endomyocardial biopsy at 4.0 (2.0-9.0) months after HTx. The level of sST2 showed positive correlation with cardiac troponin I, and N-terminal pro-B-type natriuretic peptide (all prejection) (p=0.003). However, when we studied within-subject effects of sST2 using a mixed model, the sST2 level according to the predefined time point was not different according to the presence of significant rejection (p for interaction=0.94). Although sST2 is known as a promising predictor for cardiovascular events, its role in HTx patients to predict acute allograft rejection seems to be limited.

P-wave dispersion and its relationship to aortic stiffness in patients with acute myocardial infarction after cardiac rehabilitation

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Rezzan Deniz Acar

2014-07-01

Full Text Available BACKGROUND: The aim of our study was to investigate the P-wave dispersion from standard electrocardiograms (ECGs in patients with acute myocardial infarction (AMI after cardiac rehabilitation (CR and determine its relation to arterial stiffness. METHODS: This is a prospective study included 33 patients with AMI and successfully re-vascularized by percutaneous coronary intervention (PCI underwent CR. Left ventricular ejection fraction (LVEF was measured by biplane Simpson’s method. Left atrium (LA volume was calculated. The maximum and minimum durations of P-waves (Pmax and Pmin, respectively were detected, and the difference between Pmax and Pmin was defined as P-wave dispersion (Pd = Pmax–Pmin. Aortic elasticity parameters were measured. RESULTS: LVEF was better after CR. The systolic and diastolic blood pressures decreased after CR, these differences were statistically significant. With exercise training, LA volume decreased significantly. Pmax and Pd values were significantly shorter after the CR program. The maximum and minimum P-waves and P-wave dispersion after CR were 97 ± 6 ms, 53 ± 5 ms, and 44 ± 5 ms, respectively. Aortic strain and distensibility increased and aortic stiffness index was decreased significantly. Aortic stiffness index was 0.4 ± 0.2 versus 0.3 ± 0.2, P = 0.001. Aortic stiffness and left atrial volume showed a moderate positive correlation with P-wave dispersion (r = 0.52, P = 0.005; r = 0.64, P = 0.000, respectively. CONCLUSION: This study showed decreased arterial stiffness indexes in AMI patient’s participated CR, with a significant relationship between the electromechanical properties of the LA that may raise a question of the preventive effect of CR from atrial fibrillation and stroke in patients with acute myocardial infarction.   Keywords: Cardiac Rehabilitation, P-Wave Dispersion, Aortic Stiffness, Acute Myocardial Infarction 

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...

Early detection of femoral head avascular necrosis by bone SPECT compared to MRI in renal allograft recipients

Energy Technology Data Exchange (ETDEWEB)

Kang, Do Young; Yang, Seoung Oh; Lee, Hee Kyung; Han, Duck Jong; Shin, Myung Jin [Asan Mecical Center, Seoul (Korea, Republic of)

1997-07-01

The prevalence of avascular necrosis (AVN) of femoral head in patients who receive immunosuppresive agents after renal transplantation is reported to be 4-29%. Among patients who develop AVN after renal transplantation, 80% become symptomatic within 2 years after transplantation. As the number of renal transplantation has been increased recently, early detection of femoral head AVN is very important because early surgical core decompression of femoral head can prevent collapse of the head. MRI is known to be very sensitive to diagnose femoral head AVN. However in three cases we report here, bone SPECT showed early changes of femoral head AVN, whereas MRI showed no specific abnormality. Case 1. A 53-year-old female received an allograft kidney transplantation in 1994. Preoperative bone scan was normal. She complained of both hip pain on Mar. 18 1997. Bone SPECT showed cold defect in both femoral heads but MRI showed no abnormality. After 3 months, bone SPECT and MRI showed AVN of both femoral heads. She underwent bilateral total hip replacement arthroplasty. AVN of femoral heads was confirmed by microscopic examination. Case 2. A 38-year-old female received an allograft kidney transplantation in Feb. 27 1997. Preoperative bone scan was normal. She ran a fever and creatinine was elevated from 1.2 to 2.8 mg/dL. She took high dose methylprednisolone therapy for acute reanl rejection. After two days, she complained pain in both hip joints and knee joints. Bone SPECT showed cold defects in both femoral heads but MRI showed no abnormality. A follow-up bone SPECT and MRI 20 days later revealed AVN of both femoral heads. Case 3. A 50-year-old male received an allograft kidney transplantation on Jul. 12 1995. Preoperative bone scan was normal. He complained of right hip pain on Jul, 26 1995. His bone SPECT showed cold defects in both femoral heads while MRI showed only minimal hip joint effusion. He also complained of left hip pain on Oct. 2 1995. He was admitted on Mar 17

Early detection of femoral head avascular necrosis by bone SPECT compared to MRI in renal allograft recipients

International Nuclear Information System (INIS)

Kang, Do Young; Yang, Seoung Oh; Lee, Hee Kyung; Han, Duck Jong; Shin, Myung Jin

1997-01-01

The prevalence of avascular necrosis (AVN) of femoral head in patients who receive immunosuppresive agents after renal transplantation is reported to be 4-29%. Among patients who develop AVN after renal transplantation, 80% become symptomatic within 2 years after transplantation. As the number of renal transplantation has been increased recently, early detection of femoral head AVN is very important because early surgical core decompression of femoral head can prevent collapse of the head. MRI is known to be very sensitive to diagnose femoral head AVN. However in three cases we report here, bone SPECT showed early changes of femoral head AVN, whereas MRI showed no specific abnormality. Case 1. A 53-year-old female received an allograft kidney transplantation in 1994. Preoperative bone scan was normal. She complained of both hip pain on Mar. 18 1997. Bone SPECT showed cold defect in both femoral heads but MRI showed no abnormality. After 3 months, bone SPECT and MRI showed AVN of both femoral heads. She underwent bilateral total hip replacement arthroplasty. AVN of femoral heads was confirmed by microscopic examination. Case 2. A 38-year-old female received an allograft kidney transplantation in Feb. 27 1997. Preoperative bone scan was normal. She ran a fever and creatinine was elevated from 1.2 to 2.8 mg/dL. She took high dose methylprednisolone therapy for acute reanl rejection. After two days, she complained pain in both hip joints and knee joints. Bone SPECT showed cold defects in both femoral heads but MRI showed no abnormality. A follow-up bone SPECT and MRI 20 days later revealed AVN of both femoral heads. Case 3. A 50-year-old male received an allograft kidney transplantation on Jul. 12 1995. Preoperative bone scan was normal. He complained of right hip pain on Jul, 26 1995. His bone SPECT showed cold defects in both femoral heads while MRI showed only minimal hip joint effusion. He also complained of left hip pain on Oct. 2 1995. He was admitted on Mar 17

TU-G-BRA-08: BEST IN PHYSICS (JOINT IMAGING-THERAPY): Hybrid PET-MRI Imaging of Acute Radiation Induced Cardiac Toxicity

International Nuclear Information System (INIS)

El-Sherif, O; Xhaferllari, I; Gaede, S; Sykes, J; Butler, J; Wisenberg, G; Prato, F

2015-01-01

Purpose: To identify the presence of low-dose radiation induced cardiac toxicity in a canine model using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: Research ethics board approval was obtained for a longitudinal imaging study of 5 canines after cardiac irradiation. Animals were imaged at baseline, 1 week post cardiac irradiation, and 1 month post cardiac irradiation using a hybrid PET- MRI system (Biograph mMR, Siemens Healthcare). The imaging protocol was designed to assess acute changes in myocardial perfusion and inflammation. Myocardial perfusion imaging was performed using N13-ammonia tracer followed by a dynamic PET acquisition scan. A compartmental tracer kinetic model was used for absolute perfusion quantification. Myocardial inflammation imaging was performed using F18-fluorodeoxyglucose (FDG) tracer. The standard uptake value (SUV) over a region encompassing the whole heart was used to compare FDG scans. All animals received a simulation CT scan (GE Medical Systems) for radiation treatment planning. Radiation treatment plans were created using the Pinncale3 treatment planning system (Philips Radiation Oncology Systems) and designed to resemble the typical cardiac exposure during left-sided breast cancer radiotherapy. Cardiac irradiations were performed in a single fraction using a TrueBeam linear accelerator (Varian Medical Systems). Results: The delivered dose (mean ± standard deviation) to heart was 1.8±0.2 Gy. Reductions in myocardial stress perfusion relative to baseline were observed in 2 of the 5 animals 1 month post radiation. A global inflammatory response 1 month post radiation was observed in 4 of the 5 animals. The calculated SUV at 1 month post radiation was significantly higher (p=0.05) than the baseline SUV. Conclusion: Low doses of cardiac irradiation (< 2 Gy) may lead to myocardial perfusion defects and a global inflammatory response that can be detectable as early as 1 month post irradiation

TU-G-BRA-08: BEST IN PHYSICS (JOINT IMAGING-THERAPY): Hybrid PET-MRI Imaging of Acute Radiation Induced Cardiac Toxicity

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El-Sherif, O; Xhaferllari, I; Gaede, S [Western Univeristy, London, ON (United Kingdom); London Regional Cancer Program, London, ON (United Kingdom); Sykes, J; Butler, J [Lawson Health Research Institute, London, ON (United Kingdom); Wisenberg, G; Prato, F [Western Univeristy, London, ON (United Kingdom); Lawson Health Research Institute, London, ON (United Kingdom)

2015-06-15

Purpose: To identify the presence of low-dose radiation induced cardiac toxicity in a canine model using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: Research ethics board approval was obtained for a longitudinal imaging study of 5 canines after cardiac irradiation. Animals were imaged at baseline, 1 week post cardiac irradiation, and 1 month post cardiac irradiation using a hybrid PET- MRI system (Biograph mMR, Siemens Healthcare). The imaging protocol was designed to assess acute changes in myocardial perfusion and inflammation. Myocardial perfusion imaging was performed using N13-ammonia tracer followed by a dynamic PET acquisition scan. A compartmental tracer kinetic model was used for absolute perfusion quantification. Myocardial inflammation imaging was performed using F18-fluorodeoxyglucose (FDG) tracer. The standard uptake value (SUV) over a region encompassing the whole heart was used to compare FDG scans. All animals received a simulation CT scan (GE Medical Systems) for radiation treatment planning. Radiation treatment plans were created using the Pinncale3 treatment planning system (Philips Radiation Oncology Systems) and designed to resemble the typical cardiac exposure during left-sided breast cancer radiotherapy. Cardiac irradiations were performed in a single fraction using a TrueBeam linear accelerator (Varian Medical Systems). Results: The delivered dose (mean ± standard deviation) to heart was 1.8±0.2 Gy. Reductions in myocardial stress perfusion relative to baseline were observed in 2 of the 5 animals 1 month post radiation. A global inflammatory response 1 month post radiation was observed in 4 of the 5 animals. The calculated SUV at 1 month post radiation was significantly higher (p=0.05) than the baseline SUV. Conclusion: Low doses of cardiac irradiation (< 2 Gy) may lead to myocardial perfusion defects and a global inflammatory response that can be detectable as early as 1 month post irradiation

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

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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

Referrals in acute coronary events for CARdiac catheterization: The RACE CAR trial.

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Kreatsoulas, Catherine; Sloane, Debi; Pogue, Janice; Velianou, James L; Anand, Sonia S

2010-10-01

Women with acute coronary syndromes have lower rates of cardiac catheterization (CC) than men. To determine whether sex⁄gender, age, risk level and patient preference influence physician decision making to refer patients for CC. Twelve clinical scenarios controlling for sex⁄gender, age (55 or 75 years of age), Thrombolysis in Myocardial Infarction risk score (low, moderate or high) and patient preference for CC (agreeable or refused⁄no preference expressed) were designed. Scenarios were administered to specialists across Canada using a web-based computerized survey instrument. Questions were standardized using a five-point Likert scale ranging from 1 (very unlikely to benefit from CC) to 5 (very likely to benefit from CC). Outcomes were assessed using a two-tailed mixed linear regression model. Of 237 scenarios, physicians rated men as more likely to benefit from CC than women (mean [± SE] 4.44±0.07 versus 4.25±0.07, P=0.03), adjusted for age, risk and patient preference. Low-risk men were perceived to benefit more than low-risk women (4.20±0.13 versus 3.54±0.14, Pno comment at all (5.0±0.23, 3.67±0.21, 2.95±0.14, respectively, P<0.01). Canadian specialists' decisions to refer patients for CC appear to be influenced by sex⁄gender, age and patient preference in clinical scenarios in which cardiac risk is held constant. Future investigation of possible age and sex⁄gender biases as proxies for risk is warranted.

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

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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.

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

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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.

Will sacubitril-valsartan diminish the clinical utility of B-type natriuretic peptide testing in acute cardiac care?

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Mair, Johannes; Lindahl, Bertil; Giannitsis, Evangelos; Huber, Kurt; Thygesen, Kristian; Plebani, Mario; Möckel, Martin; Müller, Christian; Jaffe, Allan S

2017-06-01

Since the approval of sacubitril-valsartan for the treatment of chronic heart failure with reduced ejection fraction, a commonly raised suspicion is that a wider clinical use of this new drug may diminish the clinical utility of B-type natriuretic peptide testing as sacubitril may interfere with B-type natriuretic peptide clearance. In this education paper we critically assess this hypothesis based on the pathophysiology of the natriuretic peptide system and the limited published data on the effects of neprilysin inhibition on natriuretic peptide plasma concentrations in humans. As the main clinical application of B-type natriuretic peptide testing in acute cardiac care is and will be the rapid rule-out of suspected acute heart failure there is no significant impairment to be expected for B-type natriuretic peptide testing in the acute setting. However, monitoring of chronic heart failure patients on sacubitril-valsartan treatment with B-type natriuretic peptide testing may be impaired. In contrast to N-terminal-proBNP, the current concept that the lower the B-type natriuretic peptide result in chronic heart failure patients, the better the prognosis during treatment monitoring, may no longer be true.

Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

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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.

A Computational Gene Expression Score for Predicting Immune Injury in Renal Allografts.

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Tara K Sigdel

Full Text Available Whole genome microarray meta-analyses of 1030 kidney, heart, lung and liver allograft biopsies identified a common immune response module (CRM of 11 genes that define acute rejection (AR across different engrafted tissues. We evaluated if the CRM genes can provide a molecular microscope to quantify graft injury in acute rejection (AR and predict risk of progressive interstitial fibrosis and tubular atrophy (IFTA in histologically normal kidney biopsies.Computational modeling was done on tissue qPCR based gene expression measurements for the 11 CRM genes in 146 independent renal allografts from 122 unique patients with AR (n = 54 and no-AR (n = 92. 24 demographically matched patients with no-AR had 6 and 24 month paired protocol biopsies; all had histologically normal 6 month biopsies, and 12 had evidence of progressive IFTA (pIFTA on their 24 month biopsies. Results were correlated with demographic, clinical and pathology variables.The 11 gene qPCR based tissue CRM score (tCRM was significantly increased in AR (5.68 ± 0.91 when compared to STA (1.29 ± 0.28; p < 0.001 and pIFTA (7.94 ± 2.278 versus 2.28 ± 0.66; p = 0.04, with greatest significance for CXCL9 and CXCL10 in AR (p <0.001 and CD6 (p<0.01, CXCL9 (p<0.05, and LCK (p<0.01 in pIFTA. tCRM was a significant independent correlate of biopsy confirmed AR (p < 0.001; AUC of 0.900; 95% CI = 0.705-903. Gene expression modeling of 6 month biopsies across 7/11 genes (CD6, INPP5D, ISG20, NKG7, PSMB9, RUNX3, and TAP1 significantly (p = 0.037 predicted the development of pIFTA at 24 months.Genome-wide tissue gene expression data mining has supported the development of a tCRM-qPCR based assay for evaluating graft immune inflammation. The tCRM score quantifies injury in AR and stratifies patients at increased risk of future pIFTA prior to any perturbation of graft function or histology.

Effects of particle size and porosity on in vivo remodeling of settable allograft bone/polymer composites.

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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.

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage.

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Mutoh, Tomoko; Mutoh, Tatsushi; Nakamura, Kazuhiro; Yamamoto, Yukiko; Tsuru, Yoshiharu; Tsubone, Hirokazu; Ishikawa, Tatsuya; Taki, Yasuyuki

2017-04-01

Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5 hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator. © 2017 John Wiley & Sons Australia, Ltd.

Angiotensin converting enzyme DD genotype is associated with acute coronary syndrome severity and sudden cardiac death in Taiwan: a case-control emergency room study.

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Chen, Ying-Hsin; Liu, Jui-Ming; Hsu, Ren-Jun; Hu, Sheng-Chuan; Harn, Horng-Jyh; Chen, Shee-Ping; Jeng, Jing-Ren; Wu, Chieh-Lin; Ho, Jar-Yi; Yu, Cheng-Ping

2012-02-15

Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms have been associated with acute coronary syndrome (ACS); however, several controversial results have also been found in different studied populations. This hospital-based, emergency room, case-control study in Taiwan retrospectively investigated 111 ACS patients, and 195 non-coronary subjects as a control group, to study the effects of ACE I/D polymorphism in the most urgent ACS patients. ACE I/D polymorphisms were determined by polymerase chain reaction-based assays and their associations with ACS risk, severity, and sudden cardiac death were determined. The ACE DD genotype was associated with ACS incidence. The DD genotype was associated with a significant 4-fold higher risk of ACS in multivariate analysis (odds ratio (OR) = 4.295; 95% confidence interval (CI): 1.436-12.851, p = 0.009), and a 3.35-fold higher risk of acute myocardial infarction. DD genotype carriers also had more than 3-fold higher risks of stenosis in all the three coronary arteries, left anterior descending artery infarction, and anterior wall infarction. In addition, the DD genotype was also associated with a higher risk of sudden cardiac death (OR = 6.484, 95% CI: 1.036-40.598, p = 0.046). This study demonstrated that the ACE DD genotype is an independent risk factor for ACS, and in particular, for acute myocardial infarction. In addition, the ACE DD genotype is also associated with greater ACS severity and a higher risk of sudden cardiac death. ACE genotyping is recommended for patients with a history of ACS, and more intensive preventive care is suggested for patients with the DD genotype.

Influence of socioeconomic status on allograft and patient survival following kidney transplantation.

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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.

Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

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Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

2017-12-01

Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of TDTH and Tc populations in organ graft rejection. I. Functional analysis of graft-infiltrating T cells

International Nuclear Information System (INIS)

Stepkowski, S.M.; Duncan, W.R.

1986-01-01

To analyze the role of T cell subpopulations in the rejection of organ allografts, we developed a new model for obtaining large numbers of graft infiltrating cells (GICs). We isolated W3/25+ Th/DTH and OX8+ Ts/c from vascularized, irradiated rat spleen allografts. W3/25+ GICs obtained from spleen allografts transplanted to normal recipients were highly effective in eliciting cardiac allograft rejection when transferred to sublethally irradiated recipients, however, the OX8+ subset was incapable of eliciting rejection. On the other hand, when OX8+ GICs were obtained from spleen allografts transplanted to previously immunized recipients, they were as efficient as the W3/25+ Th/DTH subset in eliciting cardiac allograft destruction. These results indicate that the W3/25+, OX8- T cell is required for the rejection of primary organ allografts, but that the rejection of a secondary allograft by an immune recipient may be mediated, independently, by both W3/25+ and OX8+ cells

Proposal of quality indicators for cardiac rehabilitation after acute coronary syndrome in Japan: a modified Delphi method and practice test.

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Ohtera, Shosuke; Kanazawa, Natsuko; Ozasa, Neiko; Ueshima, Kenji; Nakayama, Takeo

2017-01-27

Cardiac rehabilitation is underused and its quality in practice is unclear. A quality indicator is a measurable element of clinical practice performance. This study aimed to propose a set of quality indicators for cardiac rehabilitation following an acute coronary event in the Japanese population and conduct a small-size practice test to confirm feasibility and applicability of the indicators in real-world clinical practice. This study used a modified Delphi technique (the RAND/UCLA appropriateness method), a consensus method which involves an evidence review, a face-to-face multidisciplinary panel meeting and repeated anonymous rating. Evidence to be reviewed included clinical practice guidelines available in English or Japanese and existing quality indicators. Performance of each indicator was assessed retrospectively using medical records at a university hospital in Japan. 10 professionals in cardiac rehabilitation for the consensus panel. In the literature review, 23 clinical practice guidelines and 16 existing indicators were identified to generate potential indicators. Through the consensus-building process, a total of 30 indicators were assessed and finally 13 indicators were accepted. The practice test (n=39) revealed that 74% of patients underwent cardiac rehabilitation. Median performance of process measures was 93% (IQR 46-100%). 'Communication with the doctor who referred the patient to cardiac rehabilitation' and 'continuous participation in cardiac rehabilitation' had low performance (32% and 38%, respectively). A modified Delphi technique identified a comprehensive set of quality indicators for cardiac rehabilitation. The single-site, small-size practice test confirmed that most of the proposed indicators were measurable in real-world clinical practice. However, some clinical processes which are not covered by national health insurance in Japan had low performance. Further studies will be needed to clarify and improve the quality of care in cardiac

[Structure and functional organization of integrated cardiac intensive care].

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Scherillo, Marino; Miceli, Domenico; Tubaro, Marco; Guiducci, Umberto

2007-05-01

The early invasive strategy for the treatment of acute coronary syndromes and the increasing number of older and sicker patients requiring prolonged and more complex intensive care have induced many changes in the function of the intensive care units. These changes include the statement that specially trained cardiologists and cardiac nurses who can manage patients with acute cardiac conditions should staff the intensive care units. This document indicates the structure of the units and specific recommendations for the number of beds, monitoring system, respirators, pacemaker/defibrillators and additional equipment.

Acute respiratory tract infections: a potential trigger for the acute coronary syndrome

NARCIS (Netherlands)

Harskamp, Ralf E.; van Ginkel, Margreet W.

2008-01-01

Clinical studies suggest that acute respiratory tract infection (ARTI) may be a risk factor for the acute coronary syndrome (ACS). ARTI is associated with an increased risk for ACS up to 2 weeks prior to a cardiac event. The mechanism that may underlie this association is unclear. Infections are

Remodeling of ACL Allografts is Inhibited by Peracetic Acid Sterilization

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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

Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology.

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Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

2015-10-01

Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

Correlation of C-Reactive Protein and Cardiac Enzymes with Angiographic Severity of Coronary Artery Disease in Pakistani Patients with Acute Coronary Syndrome.

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Saleem, Ayesha; Ali, Azmat

2017-02-01

To determine the correlation of C-reactive protein (CRP) levels with the severity of coronary stenosis on angiography and the association of cardiac enzymes with the degree of stenosis in acute coronary syndrome (ACS) patients. Secondly, to compare association of angiographic severity of vascular stenosis with CRP in patients with ST segment elevation myocardial infarction (STEMI) and non-STEMI / Unstable angina (UA). Prospective, descriptive study. Khan Research Laboratories (KRL) Hospital, from October 2014 to March 2015. CRP was measured on diagnosis of ACS in 70 patients. Cardiac enzymes were measured 6 hours after the onset of chest pain. Angiographic scoring for degree of stenosis and number of culprit vessels was done. Two groups consisting of patients with STEMI (group 1) and with NSTEMI/UA (group 2) were made. No correlation was found between CRP levels and angiographic stenosis in patients with ACS (r=0.162, p>0.05). No association was found between eosinophil count and severity of stenosis (p=0.88). Rise of cardiac enzymes and degree of coronary stenosis showed a positive correlation (p Rise in cardiac enzymes still grade high in predicting severity of vascular stenosis than eosinophil count or CRP levels.

Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following cardiac arrest

Science.gov (United States)

2013-01-01

Introduction Fluid resuscitation in the critically ill often results in a positive fluid balance, potentially diluting the serum creatinine concentration and delaying diagnosis of acute kidney injury (AKI). Methods Dilution during AKI was quantified by combining creatinine and volume kinetics to account for fluid type, and rates of fluid infusion and urine output. The model was refined using simulated patients receiving crystalloids or colloids under four glomerular filtration rate (GFR) change scenarios and then applied to a cohort of critically ill patients following cardiac arrest. Results The creatinine concentration decreased during six hours of fluid infusion at 1 litre-per-hour in simulated patients, irrespective of fluid type or extent of change in GFR (from 0% to 67% reduction). This delayed diagnosis of AKI by 2 to 9 hours. Crystalloids reduced creatinine concentration by 11 to 19% whereas colloids reduced concentration by 36 to 43%. The greatest reduction was at the end of the infusion period. Fluid dilution alone could not explain the rapid reduction of plasma creatinine concentration observed in 39 of 49 patients after cardiac arrest. Additional loss of creatinine production could account for those changes. AKI was suggested in six patients demonstrating little change in creatinine, since a 52 ± 13% reduction in GFR was required after accounting for fluid dilution and reduced creatinine production. Increased injury biomarkers within a few hours of cardiac arrest, including urinary cystatin C and plasma and urinary Neutrophil-Gelatinase-Associated-Lipocalin (biomarker-positive, creatinine-negative patients) also indicated AKI in these patients. Conclusions Creatinine and volume kinetics combined to quantify GFR loss, even in the absence of an increase in creatinine. The model improved disease severity estimation, and demonstrated that diagnostic delays due to dilution are minimally affected by fluid type. Creatinine sampling should be delayed at least

Acute Cardiac Failure in a Pregnant Woman due to Thyrotoxic Crisis

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Nao Okuda

2012-01-01

Full Text Available Introduction. Cardiac failure during pregnancy is usually related to preeclampsia/eclampsia, rarely to hyperthyroidism. While hyperthyroidism can easily lead to hypertensive cardiac failure and may harm the fetus, it is sometimes difficult to distinguish hyperthyroidism from normal pregnancy. Case Presentation. We encountered a case of 41-year-old pregnant woman with hypertensive cardiac failure. Because we initially diagnosed as pre-eclampsia/eclampsia, Caesarian section was performed. However, her symptoms still persisted after delivery. After thyroid function test results taken on the day of admission were obtained on the fourth day, we could diagnose that her cardiac failure was caused by thyrotoxic crisis. Conclusions. Hypertensive cardiac failure due to hyperthyroidism during pregnancy is rare and difficult to diagnose because of similar presentation of normal pregnancy. However, physicians should be aware of the risks posed by hyperthyroidism during pregnancy.

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.

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

Defining the Intrinsic Cardiac Risks of Operations to Improve Preoperative Cardiac Risk Assessments.

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Liu, Jason B; Liu, Yaoming; Cohen, Mark E; Ko, Clifford Y; Sweitzer, Bobbie J

2018-02-01

Current preoperative cardiac risk stratification practices group operations into broad categories, which might inadequately consider the intrinsic cardiac risks of individual operations. We sought to define the intrinsic cardiac risks of individual operations and to demonstrate how grouping operations might lead to imprecise estimates of perioperative cardiac risk. Elective operations (based on Common Procedural Terminology codes) performed from January 1, 2010 to December 31, 2015 at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program were studied. A composite measure of perioperative adverse cardiac events was defined as either cardiac arrest requiring cardiopulmonary resuscitation or acute myocardial infarction. Operations' intrinsic cardiac risks were derived from mixed-effects models while controlling for patient mix. Resultant risks were sorted into low-, intermediate-, and high-risk categories, and the most commonly performed operations within each category were identified. Intrinsic operative risks were also examined using a representative grouping of operations to portray within-group variation. Sixty-six low, 30 intermediate, and 106 high intrinsic cardiac risk operations were identified. Excisional breast biopsy had the lowest intrinsic cardiac risk (overall rate, 0.01%; odds ratio, 0.11; 95% CI, 0.02 to 0.25) relative to the average, whereas aorto-bifemoral bypass grafting had the highest (overall rate, 4.1%; odds ratio, 6.61; 95% CI, 5.54 to 7.90). There was wide variation in the intrinsic cardiac risks of operations within the representative grouping (median odds ratio, 1.40; interquartile range, 0.88 to 2.17). A continuum of intrinsic cardiac risk exists among operations. Grouping operations into broad categories inadequately accounts for the intrinsic cardiac risk of individual operations.

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.

Cell-based therapies for cardiac repair : a meeting report on scientific observations and European regulatory viewpoints

NARCIS (Netherlands)

Schüssler-Lenz, Martina; Beuneu, Claire; Menezes-Ferreira, Margarida; Jekerle, Veronika; Bartunek, Jozef; Chamuleau, Steven; Celis, Patrick; Doevendans, Pieter; O'Donovan, Maura; Hill, Jonathan; Hystad, Marit; Jovinge, Stefan; Kyselovič, Ján; Lipnik-Stangelj, Metoda; Maciulaitis, Romaldas; Prasad, Krishna; Samuel, Anthony; Tenhunen, Olli; Tonn, Torsten; Rosano, Giuseppe; Zeiher, Andreas; Salmikangas, Paula

In the past decade, novel cell-based products have been studied in patients with acute and chronic cardiac disease to assess whether these therapies are efficacious in improving heart function and preventing the development of end-stage heart failure. Cardiac indications studied include acute

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.

Science.gov (United States)

Hernandez-Fuentes, Maria P; Franklin, Christopher; Rebollo-Mesa, Irene; Mollon, Jennifer; Delaney, Florence; Perucha, Esperanza; Stapleton, Caragh; Borrows, Richard; Byrne, Catherine; Cavalleri, Gianpiero; Clarke, Brendan; Clatworthy, Menna; Feehally, John; Fuggle, Susan; Gagliano, Sarah A; Griffin, Sian; Hammad, Abdul; Higgins, Robert; Jardine, Alan; Keogan, Mary; Leach, Timothy; MacPhee, Iain; Mark, Patrick B; Marsh, James; Maxwell, Peter; McKane, William; McLean, Adam; Newstead, Charles; Augustine, Titus; Phelan, Paul; Powis, Steve; Rowe, Peter; Sheerin, Neil; Solomon, Ellen; Stephens, Henry; Thuraisingham, Raj; Trembath, Richard; Topham, Peter; Vaughan, Robert; Sacks, Steven H; Conlon, Peter; Opelz, Gerhard; Soranzo, Nicole; Weale, Michael E; Lord, Graham M

2018-02-01

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application. © 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

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.

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

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.

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

Drug-Induced Rhabdomyolysis with Elevated Cardiac Troponin T

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Gro Egholm

2015-01-01

Full Text Available The essential role of cardiac troponin in the diagnosis of acute myocardial infarction has led to the development of high-sensitivity assays, which are able to detect very small amounts of myocardial necrosis. The high-sensitivity cardiac troponin T assay, however, is not entirely specific for myocardial injury. This case report describes a 48-year-old woman, who, two years after cardiac transplantation, presented with rhabdomyolysis. During the course of the disease, her troponin T level was elevated on repeated occasions, but other definitive evidence of myocardial injury was not found. Asymptomatic cardiac troponin T elevations during rhabdomyolysis may be due to either cardiac involvement or false positive results stemming from skeletal muscle injury.

Leiomyoma in a Renal Allograft

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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.

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

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

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.

The Effect of Local Irradiation in Prevention and Reversal of Acute Rejection of Transplanted Kidney with High-dose Steroid Pulse

International Nuclear Information System (INIS)

Kim, I. H.; Ha, S. W.; Park, C. I.; Kim, S. T.

1986-01-01

From 1979 to 1984, 39 local allograft irradiations were given to 29 patients: 10 irradiations were administered for prevention and 29 for reversal of acute rejection of transplanted kidney. Three doses of 150 cGy every other day were combined with high-dose of methylprednisolone pulse (1 gm/day) for 3 days. For prevention of acute rejection, local irradiation was delivered on the days 1, 3, and 5 after the transplantation, and for reversal, irradiation started after the diagnosis of acute rejection. Eight out of 10 patients irradiated for prevention had acute allograft rejection, and, what is more, there was no surviving graft at 15 months after transplantation. Reversal of acute rejection was achieved in 71%. When the pre-irradiation level of serum creatinine was below 5.5 mg%, the reversal rate was 93%, but above 5.5 mg% the reversal rate was only 17% (p<0.01). Reirradiation after failure was not successful. Among 15 reversed patients, 7 (47%) had subsequent rejection (s). The functional graft survivals at 6 month, 1, 2, and 3 year were 70%, 65%, 54%, and 65%, respectively. Therapeutic irradiation resulted in better graft survival when serum creatinine was below 5.5 mg% (p<0.001) or when irradiation started within 15 days after the diagnosis of acute rejection (p<0.001)

The ECG Vertigo in Diabetes and Cardiac Autonomic Neuropathy

OpenAIRE

Voulgari, Christina; Tentolouris, Nicholas; Stefanadis, Christodoulos

2011-01-01

The importance of diabetes in the epidemiology of cardiovascular diseases cannot be overemphasized. About one third of acute myocardial infarction patients have diabetes, and its prevalence is steadily increasing. The decrease in cardiac mortality in people with diabetes is lagging behind that of the general population. Cardiovascular disease is a broad term which includes any condition causing pathological changes in blood vessels, cardiac muscle or valves, and cardiac rhythm. The ECG offers...

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

Distance to invasive heart centre, performance of acute coronary angiography, and angioplasty and associated outcome in out-of-hospital cardiac arrest: a nationwide study.

Science.gov (United States)

Tranberg, Tinne; Lippert, Freddy K; Christensen, Erika F; Stengaard, Carsten; Hjort, Jakob; Lassen, Jens Flensted; Petersen, Frants; Jensen, Jan Skov; Bäck, Caroline; Jensen, Lisette Okkels; Ravkilde, Jan; Bøtker, Hans Erik; Terkelsen, Christian Juhl

2017-06-01

To evaluate whether the distance from the site of event to an invasive heart centre, acute coronary angiography (CAG)/percutaneous coronary intervention (PCI) and hospital-level of care (invasive heart centre vs. local hospital) is associated with survival in out-of-hospital cardiac arrest (OHCA) patients. Nationwide historical follow-up study of 41 186 unselected OHCA patients, in whom resuscitation was attempted between 2001 and 2013, identified through the Danish Cardiac Arrest Registry. We observed an increase in the proportion of patients receiving bystander CPR (18% in 2001, 60% in 2013, P acute CAG/PCI (5% in 2001, 27% in 2013, P acute CAG/PCI annually in each region was defined as the CAG/PCI index. The following variables were associated with lower mortality in multivariable analyses: direct admission to invasive heart centre (HR 0.91, 95% CI: 0.89-0.93), CAG/PCI index (HR 0.33, 95% CI: 0.25-0.45), population density above 2000 per square kilometre (HR 0.94, 95% CI: 0.89-0.98), bystander CPR (HR 0.97, 95% CI: 0.95-0.99) and witnessed OHCA (HR 0.87, 95% CI: 0.85-0.89), whereas distance to the nearest invasive centre was not associated with survival. Admission to an invasive heart centre and regional performance of acute CAG/PCI were associated with improved survival in OHCA patients, whereas distance to the invasive centre was not. These results support a centralized strategy for immediate post-resuscitation care in OHCA patients. © The Author 2017. Published on behalf of the European Society of Cardiology.

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 ...

Ulinastatin administration is associated with a lower incidence of acute kidney injury after cardiac surgery: a propensity score matched study.

Science.gov (United States)

Wan, Xin; Xie, Xiangcheng; Gendoo, Yasser; Chen, Xin; Ji, Xiaobing; Cao, Changchun

2016-02-17

Systemic inflammation is involved in the development of acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB). Ulinastatin, a urinary trypsin inhibitor (UTI), possesses a variety of anti-inflammatory effects. Therefore, we hypothesized that the administration of ulinastatin would reduce the occurrence of AKI in patients undergoing cardiac surgery with CPB. A retrospective propensity score matched analysis was used to evaluate the effect of ulinastatin on the development of AKI in patients undergoing first documented cardiac surgery with CPB between January 2008 and December 2012 in our hospital. Multiple logistic regression models were also employed to identify the association between UTI administration and development of AKI. A total of 2072 patients who underwent cardiac surgery with CPB met the inclusion criteria. Before propensity score matching, variables such as age, baseline creatinine, CPB duration, red blood cells transfused, and hematocrit were statistically different between the ulinastatin (UTI) group and the control group. On the basis of propensity scores, 409 UTI patients were successfully matched to the 409 patients from among those 1663 patients without UTI administration. After propensity score matching, no statistically significant differences in the baseline characteristics were found between the UTI group and the control group. The propensity score matched cohort analysis revealed that AKI and the need for renal replacement therapy occurred more frequently in the control group than in the UTI group (40.83% vs. 30.32%, P = 0.002; 2.44% vs. 0.49%, P = 0.02, respectively). However, there were no significant differences in mortality, length of intensive care unit stay, and length of hospital stay between the UTI group and the control group. Using multivariate logistic regression analysis, we found ulinastatin played a protective role in the development of AKI after cardiac surgery (odds ratio 0.71, 95% confidence

PREVENTION OF LEFT VENTRICLE SYSTOLIC DYSFUNCTION IN PATIENTS WITH ACUTE CORONARY SYNDROME WITH ST SEGMENT ELEVATION AFTER CARDIAC REVASCULARIZATION

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A. L. Alyavi

2016-01-01

Full Text Available Aim. To study effects of bioflavonoid quercetin (corvitin on left ventricle (LV systolic dysfunction in patients with acute coronary syndrome with ST segment elevation (ACS+ST after cardiac revascularization.Material and methods. 60 patients with ACS+ST (44,2±1,3 y.o. were examined. Patients were admitted to hospital within 6 hours after complaints beginning. Patients were randomized in two groups. 30 patients of group A had standard therapy and cardiac revascularization. 30 patients of group B received corvitin additionally to standard therapy before cardiac revascularization. Echocardiography initially and stress-echocardiography with dobutamine after status stabilization (at 8-10 days of disease were performed.Results. Dobutamine test (with low and high doses showed myocardial viability in patients of group B. Patients of group A had irreversible LV systolic dysfunction in 32 % of segments. Corvitin slowed down LV dilatation progression in patients with ACS+ST. It resulted in the end-diastolic and end-systolic indexes did not change within 10 days. The LV ejection fraction was more increased in patients of group B in comparison with patients of group A.Conclusion. The early corvitin prescribing has positive effects on LV systolic function and prevents post-reperfusion complications.