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Sample records for acute cardiac rejection

  1. Prediction of acute cardiac rejection using radionuclide techniques

    Radionuclide scanning of the donor left ventricle using technetium-99m-labelled red cells was used to monitor acute rejection after heterotopic heart transplantation and compared with histopathological evidence of rejection obtained at examination of an endomyocardial biopsy specimen. The ejection fraction and end-diastolic, end-systolic and stroke volumes were calculated at each examination; an equation was derived from these data to predict the degree of acute rejection, using histopathological examination of endomyocardial biopsy specimens as criteria of the presence and severity of rejection. A highly significant multiple correlation between radionuclide scanning parameters and endomyocardial biopsy was found. The advantages of non-invasive radionuclide scanning over the invasive procedure of endomyocardial biopsy are discussed

  2. Prediction of acute cardiac rejection using radionuclide techniques

    Novitzky, D.; Bonioszczuk, J.; Cooper, D.K.C.; Isaacs, S.; Rose, A.G.; Smith, J.A.; Uys, C.J.; Barnard, C.N.; Fraser, R. (Cape Town Univ. (South Africa))

    1984-01-07

    Radionuclide scanning of the donor left ventricle using technetium-99m-labelled red cells was used to monitor acute rejection after heterotopic heart transplantation and compared with histopathological evidence of rejection obtained at examination of an endomyocardial biopsy specimen. The ejection fraction and end-diastolic, end-systolic and stroke volumes were calculated at each examination; an equation was derived from these data to predict the degree of acute rejection, using histopathological examination of endomyocardial biopsy specimens as criteria of the presence and severity of rejection. A highly significant multiple correlation between radionuclide scanning parameters and endomyocardial biopsy was found. The advantages of non-invasive radionuclide scanning over the invasive procedure of endomyocardial biopsy are discussed.

  3. Antimyosin imaging in acute myocardial infarction and cardiac transplant rejection

    Antimyosin imaging both diagnosed and quantitated heterotopic cardiac transplant rejection in a small number of dogs with either recent or remote transplantation. The authors describe study in humans which showed 80% diagnostic accuracy of planar antimyosin imaging in patients with a wide range of times posttransplantation. A larger multicenter study including SPECT imaging will either confirm or extend these preliminary findings. Multiple injections of antimyosin will probably be safe if HAMA levels are followed

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

    Li Li

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

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

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

  6. Comparative immunohistologic studies in an adoptive transfer model of acute rat cardiac allograft rejection

    It has been shown that fulminant acute rejection of rat cardiac allografts across a full haplotype disparity may occur as a direct result of adoptive transfer of sensitized W3/25+ MRC OX8- SIg- T helper/DTH syngeneic spleen cells to sublethally irradiated recipients. In order to establish the immunohistologic parameters of this form of rejection, allografts and recipient lymphoid tissue were analyzed using a panel of monoclonal antibodies of known cellular distribution. These data were compared with those obtained following reconstitution of irradiated allograft recipients with unseparated sensitized spleen cells, with unreconstituted irradiated donor recipient pairs, with unmodified first-set rejection, and with induced myocardial infarction of syngeneic heart grafts transplanted to normal and to sublethally irradiated recipients. Rejecting cardiac allografts transplanted to all reconstituted irradiated recipients were characterized by extensive infiltration with MRC OX8+ (T cytotoxic-suppressor, natural killer) cells even when this subset was virtually excluded from the reconstituting inocula. A similar proportional accumulation of MRC OX8+ cells observed at the infarct margins of syngeneic heart grafts transplanted to irradiated unreconstituted recipients greatly exceeded that present in normal nonirradiated controls. These data provide evidence that under conditions of heavy recipient irradiation, MRC OX8+ cells may be sequestered within heart grafts in response to nonspecific injury unrelated to the rejection process

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

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

    1993-01-01

    Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...... systems have evolved. Most recently, the International Grading System was introduced in The Journal of Heart and Lung Transplantation. In this study the interobserver reproducibility of both the Stanford Classification and the International Grading System is evaluated using Kappa statistics. Three...

  8. Assessment of sub-clinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy

    Comparing the diagnostic value of multi-sequential cardiac magnetic resonance imaging (CMR) with endomyocardial biopsy (EMB) for sub-clinical cardiac allograft rejection. One hundred and forty-six examinations in 73 patients (mean age 53 ± 12 years, 58 men) were performed using a 1.5 Tesla system and compared to EMB. Examinations included a STIR (short tau inversion recovery) sequence for calculation of edema ratio (ER), a T1-weighted spin-echo sequence for assessment of global relative enhancement (gRE), and inversion-recovery sequences to visualize late gadolinium enhancement (LGE). Histological grade ≥1B was considered relevant rejection. One hundred and twenty-seven (127/146 = 87 %) EMBs demonstrated no or mild signs of rejection (grades ≤1A) and 19/146 (13 %) a relevant rejection (grade ≥1B). Sensitivity, specificity, positive predictive, and negative predictive values were as follows: ER: 63 %, 78 %, 30 %, and 93 %; gRE: 63 %, 70 %, 24 %, and 93 %; LGE: 68 %, 36 %, 13 %, and 87 %; with the combination of ER and gRE with at least one out of two positive: 84 %, 57 %, 23 %, and 96 %. ROC analysis revealed an area under the curve of 0.724 for ER and 0.659 for gRE. CMR parameters for myocarditis are useful to detect sub-clinical acute cellular rejection after heart transplantation. Comparable results to myocarditis can be achieved with a combination of parameters. (orig.)

  9. Assessment of sub-clinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy

    Krieghoff, Christian; Hildebrand, Lysann; Grothoff, Matthias; Lehmkuhl, Lukas; Luecke, Christian; Andres, Claudia; Nitzsche, Stefan; Riese, Franziska; Gutberlet, Matthias [University Leipzig - Heart Centre, Department of Diagnostic and Interventional Radiology, Leipzig (Germany); Barten, Markus J.; Strueber, Martin; Mohr, Friedrich Wilhelm [University Leipzig - Heart Centre, Department of Cardiac Surgery, Leipzig (Germany)

    2014-10-15

    Comparing the diagnostic value of multi-sequential cardiac magnetic resonance imaging (CMR) with endomyocardial biopsy (EMB) for sub-clinical cardiac allograft rejection. One hundred and forty-six examinations in 73 patients (mean age 53 ± 12 years, 58 men) were performed using a 1.5 Tesla system and compared to EMB. Examinations included a STIR (short tau inversion recovery) sequence for calculation of edema ratio (ER), a T1-weighted spin-echo sequence for assessment of global relative enhancement (gRE), and inversion-recovery sequences to visualize late gadolinium enhancement (LGE). Histological grade ≥1B was considered relevant rejection. One hundred and twenty-seven (127/146 = 87 %) EMBs demonstrated no or mild signs of rejection (grades ≤1A) and 19/146 (13 %) a relevant rejection (grade ≥1B). Sensitivity, specificity, positive predictive, and negative predictive values were as follows: ER: 63 %, 78 %, 30 %, and 93 %; gRE: 63 %, 70 %, 24 %, and 93 %; LGE: 68 %, 36 %, 13 %, and 87 %; with the combination of ER and gRE with at least one out of two positive: 84 %, 57 %, 23 %, and 96 %. ROC analysis revealed an area under the curve of 0.724 for ER and 0.659 for gRE. CMR parameters for myocarditis are useful to detect sub-clinical acute cellular rejection after heart transplantation. Comparable results to myocarditis can be achieved with a combination of parameters. (orig.)

  10. Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation

    Nuclear magnetic resonance (NMR) imagings have been applied to the observation of tissue sodium-23 in myocardium undergoing cardiac rejection. Six canine donor hearts were heterotopically transplanted in the recipient's chest cavity. The dogs were then killed and sodium-23 image of the excised donor hearts were obtained using a high field NMR imaging system (1.5 Tesla, Magnetom). Proton NMR imaging was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathologic findings such as mild, moderate and severe rejection. The correlation coefficients between rejection score, and T1, T2 times and sodium NMR signal intensity were 0.79, 0.70 and 0.80, respectively. The moderate or severe rejected myocardium were clearly visible as areas of increased sodium NMR signal. These data suggested that increase of sodium may be mainly caused by the myocardial cellular necrosis. Sodium NMR will allow us to evaluate the location and extent of rejected myocardium undergoing heart transplantation. (author)

  11. Impact of animal strain on gene expression in a rat model of acute cardiac rejection

    Norsworthy Kelly J

    2009-06-01

    Full Text Available Abstract Background The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR. Using a rat heart transplant model and 2 different rat strains (Dark Agouti, and Brown Norway, microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC. Results In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ≥ 3. Only 13 genes were affected by both strain and rejection, which was Conclusion In ACR, genetic background has a large impact on the transcriptome of immune cells, but not heart tissue. Gene expression studies of ACR should avoid study designs that require cross strain comparisons between leukocytes.

  12. Myocardial scintigraphy with gallium-67 in the detection of cardiac acute rejection

    In order to evaluate the myocardial scintigraphy with Gallium-67 potentiality in the detection of acute rejection phenomenon, 105 studies were performed in 20 patients after they had a heart transplantation. The scintigraphic images were obtained by a conventional camera-computer system. These images were acquired 48 hours after all the patients were given an intravenous injection of 111 MBq of Gallium-67 Citrate. The biopsies were done according to the Mason technique and the histological analysis followed the Billingham standards. (author)

  13. Thallium kinetics in rat cardiac transplant rejection

    Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection

  14. Thallium kinetics in rat cardiac transplant rejection

    Barak, J.H.; LaRaia, P.J.; Boucher, C.A.; Fallon, J.T.; Buckley, M.J.

    1988-04-01

    Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection.

  15. Successful use of the TandemHeart percutaneous ventricular assist device as a bridge to recovery for acute cellular rejection in a cardiac transplant patient.

    Velez-Martinez, M; Rao, K; Warner, J; Dimaio, J; Ewing, G; Mishkin, J D; Mammen, P P A; Drazner, M H; Markham, D W; Patel, P C

    2011-12-01

    In this report, we presented a patient who benefited from hemodynamic support with the TandemHeart percutaneous ventricular assist device (pVAD; Cardiac Assist, Inc) implantation in the setting of early acute graft rejection 2 months after orthotopic heart transplant. The TandemHeart initially had been used for temporary hemodynamic assistance during postcardiotomy heart failure and high-risk coronary interventions. More recently, its use in patients with cardiogenic shock from acute myocardial infarction, fulminant myocarditis, and critical aortic stenosis has been reported. To our knowledge, this is one of the first reported cases in which the TandemHeart pVAD served as a successful device for support during acute cardiac transplant rejection. PMID:22172864

  16. Rejection in the cardiac transplant

    Standard chest radiography remains the most frequent applied method for monitoring post surgical cardiac transplant patients. Evidence suggests that after the 1st month cardiac enlargement is indeed a useful indicator of rejection, sometimes being caused by pericardial effusion and/or changes in left ventricular mass. Opportunistic infections, either pulmonary lesions or mediastinal abscesses, as well as malignant tumours may all occur and require evaluation or exclusion. Conventional computed transmission tomography is an excellent technique for surveying the entire thorax relatively non-invasively and is recommended whenever pulmonary, cardiac or mediastinal changes are unexplained. Coronary arteriography with or without digital subtraction remains the definitive method for examining the coronary arteries. Left ventricular function can be evaluated with either angiography or other non-invasive methods including such techniques as echocardiography and nuclear medicine. More recently monoclonal antibody labels for antimyosin show promise for identifying rejection. Ultrafast CT scanning is now available in a number of centres. It allows millisecond cross-sectional cine-tomography of the heart as well as of the whole chest, and also provides 3-D quantitative analyses of end-diastolic and systolic function including regional wall thickening dynamics and estimations of myocardial mass. Right, as well as left-sided cardiac chambers, are demonstrated routinely during the same ultrafast CT procedure. MRI, like ultrafast CT, is a new technique still being explored. MRI as well as MR spectroscopy are regarded as diagnostic radiology procedures. (author). 32 refs.; 3 figs.; 3 tabs

  17. Macrophage Uptake of Ultra-Small Iron Oxide Particles for Magnetic Resonance Imaging in Experimental Acute Cardiac Transplant Rejection

    Purpose: To discriminate between acutely rejecting and non-rejecting transplanted hearts using a blood pool contrast agent and T2 magnetic resonance imaging (MRI) in a clinical 1.5T scanner. Material and Methods: Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. One allogeneic and one syngeneic group each received either the ultra-small iron oxide particle (USPIO), at two different doses, or no contrast agent at all. MRI was performed on postoperative day 6. Immediately after the MR scanning, contrast agent was injected and a further MRI was done 24 h later. Change in T2 was calculated. Results: No significant difference in change in T2 could be seen between rejecting and non-rejecting grafts in either of the doses, or in the control groups. There was a difference between the allogeneic group that received the higher contrast agent dose and the allogeneic group that did not receive any contrast agent at all. Conclusion: In our rat model, measurements of T2 after myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not useful for the diagnosis of acute rejection

  18. Macrophage Uptake of Ultra-Small Iron Oxide Particles for Magnetic Resonance Imaging in Experimental Acute Cardiac Transplant Rejection

    Penno, E.; Johnsson, C.; Johansson, L.; Ahlstroem, H. [Uppsala Univ. Hospital (Sweden). Depts. of Diagnostic Radiology and of Transplantation Surgery

    2006-04-15

    Purpose: To discriminate between acutely rejecting and non-rejecting transplanted hearts using a blood pool contrast agent and T2 magnetic resonance imaging (MRI) in a clinical 1.5T scanner. Material and Methods: Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. One allogeneic and one syngeneic group each received either the ultra-small iron oxide particle (USPIO), at two different doses, or no contrast agent at all. MRI was performed on postoperative day 6. Immediately after the MR scanning, contrast agent was injected and a further MRI was done 24 h later. Change in T2 was calculated. Results: No significant difference in change in T2 could be seen between rejecting and non-rejecting grafts in either of the doses, or in the control groups. There was a difference between the allogeneic group that received the higher contrast agent dose and the allogeneic group that did not receive any contrast agent at all. Conclusion: In our rat model, measurements of T2 after myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not useful for the diagnosis of acute rejection.

  19. Cellular and Functional Imaging of Cardiac Transplant Rejection

    Wu, Yijen L.; Ye, Qing

    2011-01-01

    Heart transplantation is now an established treatment for patients suffering from end-stage heart diseases. With the advances in immunosuppressive treatment, the survival rate for transplant patients has improved greatly. However, allograft rejection, both acute and chronic, after heart transplantation is still a limitation leading to morbidity and mortality. The current clinical gold standard for screening rejection is endomyocardial biopsy (EMB), which is not only invasive, but also error-prone, due to the limited sample size and the site location of sampling. It would be highly desirable to have reliable and noninvasive alternatives for EMB in monitoring cardiac allograft rejection. The objective of this review is to highlight how cardiovascular imaging can contribute to noninvasively detecting and to evaluating both acute and chronic allograft rejection after heart transplantation, in particular, cardiovascular MRI (CMRI); and how CMRI can assess both immune cell infiltration at the rejecting organ, and the cardiac dysfunctions resulting from allograft rejection. PMID:21359095

  20. GATED SPECT IN PATIENTS WITH BIOPSY-NEGATIVE CARDIAC TRANSPLANT REJECTION

    E. N. Ostroumov; V. M. Zakharevich; E. D. Kotina; N. N. Mojeiko; A. G. Kupriyanova; E. I. Ryaboshtanova; B. N. Morozov; N.Z. Meboniya; Mironov, S. V.; A. Y. Kormer; I. M. Ilynsky; L. V. Beletskaya; E. N. Kazakov

    2009-01-01

    Humoral rejection of the cardiac allograft is still a challenging problem associated with high incidence of graft loss and patient mortality. These episodes of rejection are often more severe, and more difficult to treat, than classical acute cellular rejection. Hemodynamic compromise, in the absence of acute cellular rejection, called biopsy-negative rejection occurs in 10 to 20% of cardiac allograft recipients. The assessment of hemodynamic compromise can provide functional data in transpla...

  1. GATED SPECT IN PATIENTS WITH BIOPSY-NEGATIVE CARDIAC TRANSPLANT REJECTION

    E. N. Ostroumov

    2009-05-01

    Full Text Available Humoral rejection of the cardiac allograft is still a challenging problem associated with high incidence of graft loss and patient mortality. These episodes of rejection are often more severe, and more difficult to treat, than classical acute cellular rejection. Hemodynamic compromise, in the absence of acute cellular rejection, called biopsy-negative rejection occurs in 10 to 20% of cardiac allograft recipients. The assessment of hemodynamic compromise can provide functional data in transplant patients that is complementary to myocardial biopsies if the biopsy can miss significant rejection. We present three cases of the biopsy-negative rejection. All patients have studied with gated SPECT phase analysis. 

  2. Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts

    111In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium 99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and sign of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium 99m pyrophosphate accumulation (r=0.88) but was poorly correlated with labelled antibody uptake (r=0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labeled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium 99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin. (orig.)

  3. Antimyosin imaging in cardiac transplant rejection

    Johnson, L.L.; Cannon, P.J. (Department of Medicine, College of Physicians and Surgeons, Columbia University, New York (United States))

    1991-09-01

    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references.

  4. Antimyosin imaging in cardiac transplant rejection

    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references

  5. Complement and hyper acute rejection

    Al-Rabia Mohammed

    2009-01-01

    Full Text Available Organ transplantation has been a major development in clinical medicine but its success has been marred by the immune system′s capacity to respond to "non-self" cells and tissues. A full molecular understanding of this mechanism and the myriad triggers for immune rejection is yet to be elucidated. Consequently, immunosuppressive drugs remain the mainstay of post-transplant ma-nagement; however, these interventions have side effects such as increased incidence of cancer, post-transplant lymphoproliferative disorders, susceptibility to infection if not managed appro-priately and the inconvenience to the patient of lifelong treatment. Novel therapeutic approaches based on molecular understanding of immunological processes are thus needed in this field. The notion that factors influencing successful transplants might be of use as therapeutic approaches is both scientifically and medically appealing. Recent developments in the understanding of successful transplants are expected to provide new opportunities for safer transplantation. This article reviews the present understanding of the molecular basis of rejection and the role of complement in this process as well as the possibility of generating "intelligent" therapy that better target crucial components of hyper-acute rejections.

  6. Nucleic Acid Drugs for Prevention of Cardiac Rejection

    Jun-ichi Suzuki

    2009-01-01

    Full Text Available Heart transplantation has been broadly performed in humans. However, occurrence of acute and chronic rejection has not yet been resolved. Several inflammatory factors, such as cytokines and adhesion molecules, enhance the rejection. The graft arterial disease (GAD, which is a type of chronic rejection, is characterized by intimal thickening comprised of proliferative smooth muscle cells. Specific treatments that target the attenuation of acute rejection and GAD formation have not been well studied in cardiac transplantation. Recent progress in the nucleic acid drugs, such as antisense oligodeoxynucleotides (ODNs to regulate the transcription of disease-related genes, has important roles in therapeutic applications. Transfection of cis-element double-stranded DNA, named as “decoy,” has been also reported to be a useful nucleic acid drug. This decoy strategy has been not only a useful method for the experimental studies of gene regulation but also a novel clinical strategy. In this paper, we reviewed the experimental results of NF-κB, E2F, AP-1, and STAT-1 decoy and other ODNs using the experimental heart transplant models.

  7. Monitoring of Acute Rejection after Orthotopic Heart Tranplantation

    Meng chun ying; Huang ke li; Luo bin; Wen ding guo

    2006-01-01

    Objectives To study the monitoring of rejection after orthotopic heart thansplantation.Methods From 1998 to 2005, 10 othotopic heart thansplans were performed, and acute rejection was monitored by endomyocardial biopsy as well as by clinical features, ECG, ultrasonocardiography and blood serum determination of Tropin I, and by the combination of these methods, we analysed the monitoring of acute rejection after the heart transplantation. Results With the combination of clinical features, ECG, ultrasonocardiography and blood serum test, 5 occurences of acute rejection were judged in the postoperative course, which were comfirmed by endomyocardial biopsy to be 2 acute rejections in Ⅰ b degree, 3 acute rejections in Ⅲ a degree. Endomyocardial biopsy were routinely performed 21 times postoperatively in which there were 1 acute rejection in Ⅰ a degree and 5 acute rejections in Ⅰ b degree. Conclusions Acute rejection is an important factor influencing the postoperative course of heart transplantation, so it is imperative to have an intime, effective and planned monitoring procedure for acute rejection. Endomyocardial biopsy is a sensitive and reliable method in diagnosis of acute rejection, but it is invasive and probable for some complications. The noninvasive method such as clinical features, ECG,ultrasonocardiography and blood serum test can be used as additive means in the diagnosis of acute rejection.Endomyocardial biopsy should be combined with some noninvasive methods in monitoring acute rejection after the heart transplantation.

  8. Acute appendicitis mistaken as acute rejection in renal transplant recipients.

    Talwalkar N; Javali D; Venkatesh K; Iyer S; Venkatesh M; Joshi U

    1994-01-01

    Case histories of 2 renal transplant recipients are reported who had presenting features of fever, leukocytosis and pain/tenderness over right iliac fossa and were diagnosed to be due to acute appendicitis rather than more commonly suspected acute rejection episode which has very similar features. Diagnosis of acute appendicitis was suspected on the basis of rectal examination and later confirmed by laparotomy. The purpose of this communication is to emphasize the need for proper diagnosis in...

  9. Detection of cardiac transplant rejection with radiolabeled lymphocytes

    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy

  10. Detection of cardiac transplant rejection with radiolabeled lymphocytes. [Rats

    Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-03-01

    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy.

  11. Acute Rejection and Humoral Sensitization in Lung Transplant Recipients

    Martinu, Tereza; Chen, Dong-Feng; Palmer, Scott M

    2009-01-01

    Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent develop...

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

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

    2000-12-01

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

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

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

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

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

    2009-01-01

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

  15. Acute appendicitis mistaken as acute rejection in renal transplant recipients.

    Talwalkar N

    1994-01-01

    Full Text Available Case histories of 2 renal transplant recipients are reported who had presenting features of fever, leukocytosis and pain/tenderness over right iliac fossa and were diagnosed to be due to acute appendicitis rather than more commonly suspected acute rejection episode which has very similar features. Diagnosis of acute appendicitis was suspected on the basis of rectal examination and later confirmed by laparotomy. The purpose of this communication is to emphasize the need for proper diagnosis in patient with such presentation; otherwise wrong treatment may be received.

  16. LATE ACUTE REJECTION IN LIVER TRANSPLANT: A SYSTEMATIC REVIEW

    Nacif, Lucas Souto; Pinheiro, Rafael Soares; PÉCORA, Rafael Antônio de Arruda; Ducatti, Liliana; ROCHA-SANTOS, Vinicius; Andraus, Wellington; D'ALBUQUERQUE, Luiz Carneiro

    2015-01-01

    Introduction: Late acute rejection leads to worse patient and graft survival after liver transplantation. Aim: To analyze the reported results published in recent years by leading transplant centers in evaluating late acute rejection and update the clinical manifestations, diagnosis and treatment of liver transplantation. Method: Systematic literature review through Medline-PubMed database with headings related to late acute rejection in articles published until November 2013 was done. Were a...

  17. Acute pulmonary rejection in heart and lung transplant recipients

    Acute pulmonary rejection occurs in up to 50% of patients undergoing heart and lung transplant procedures. These patients are also susceptible to volume overload and pneumonia. To evaluate the radiographic and high-resolution CT appearances of acute pulmonary rejection, we compared chest radiographs and high-resolution CT scans with the clinical findings and with histologic and lavage data from 91 serial transbronchial biopsies in 13 patients. The radiographic appearance of acute pulmonary rejection is characterized by prominent septal lines and pleural effusions. The authors conclude that in the appropriate clinical setting, the appearance of new pleural effusions and prominent septal lines is highly suggestive of acute pulmonary rejections

  18. Cellular and Functional Imaging of Cardiac Transplant Rejection

    Wu, Yijen L.; Ye, Qing; Ho, Chien

    2011-01-01

    Heart transplantation is now an established treatment for patients suffering from end-stage heart diseases. With the advances in immunosuppressive treatment, the survival rate for transplant patients has improved greatly. However, allograft rejection, both acute and chronic, after heart transplantation is still a limitation leading to morbidity and mortality. The current clinical gold standard for screening rejection is endomyocardial biopsy (EMB), which is not only invasive, but also error-p...

  19. P-31 MR spectroscopy of acute rejection in transplanted rat hearts

    To investigate the potential utility of P-31 NMR spectroscopy in the diagnosis of acute cardiac allograft rejection, the authors obtained high resolution in vitro spectra of perchloric acid extracts of freeze clamped transplanted rat hearts. These preliminary results suggest P-32 NMR spectroscopy may have utility in monitoring rejection in heart transplantation. In the acutely rejecting allografts they observed a marked increase in several resonances in the region downfield (to the left) from phosphocreatine (PCr) compared with the isografts. Specifically, the resonance of inorganic phosphate (Pi) which accounts for 55% - 65% of the total signal in the downfield region increased 1.85-fold. A fourfold increase was observed in the largest of three resonances present in the monophosphate region. Located at a chemical shift of 4.3 ppm, this resonance constituted 33% of the total signal in the downfield region. The PCr/B-ATP ratio decreased only slightly in the acutely rejecting allograft

  20. Imaging-based diagnosis of acute renal allograft rejection

    Thölking, Gerold; Schuette-Nuetgen, Katharina; Kentrup, Dominik; Pawelski, Helga; Reuter, Stefan

    2016-01-01

    Kidney transplantation is the best available treatment for patients with end stage renal disease. Despite the introduction of effective immunosuppressant drugs, episodes of acute allograft rejection still endanger graft survival. Since efficient treatment of acute rejection is available, rapid diagnosis of this reversible graft injury is essential. For diagnosis of rejection, invasive core needle biopsy of the graft is the “gold-standard”. However, biopsy carries the risk of significant graft injury and is not immediately feasible in patients taking anticoagulants. Therefore, a non-invasive tool assessing the whole organ for specific and fast detection of acute allograft rejection is desirable. We herein review current imaging-based state of the art approaches for non-invasive diagnostics of acute renal transplant rejection. We especially focus on new positron emission tomography-based as well as targeted ultrasound-based methods. PMID:27011915

  1. Bronchoalveolar Immunologic Profile of Acute Human Lung Transplant Allograft Rejection

    Gregson, Aric L.; Hoji, Aki; Saggar, Rajan; Ross, David J; Kubak, Bernard M; Jamieson, Beth D.; Weigt, S. Samuel; Lynch, Joseph P.; Ardehali, Abbas; Belperio, John A.; Yang, Otto O

    2008-01-01

    Bronchoalveolar lavage fluid (BALF) offers a potential means to diagnose acute rejection and could provide insight into the immune mechanisms responsible for lung allograft rejection. Transbronchial biopsies from 29 bronchoscopic procedures were assessed for rejection. Concurrent BALF lymphocyte subsets were examined by flow cytometry, including CD4+ and CD8+ T cells and their activation status via CD38 expression, NK, NK-like T (NT), B, T regulatory (Treg) and invariant receptor NK-T cells (...

  2. Acute rejection episodes after kidney transplantation

    Hamida Fethi

    2009-01-01

    Full Text Available Acute rejection episodes (AREs are a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains, at least partially, the improvement seen in the results of transplantation in recent years. The objectives of this study are to analyze the incidence and severity of AREs, their risk factors and their influence on graft and patient survival. We retrospectively studied 280 kidney transplants performed in adults at the Charles Nicolle Hospital, Tunis, between 1986 and 2004. The diagnosis of ARE was based on clinical data and response to treatment. Allograft biopsies were performed in ten cases. The treatment of AREs consisted of pulse methylprednisolone and anti-thymocyte globulin. There were 186 males (66.4% and 94 females (33.6%, and their mean age was 31 ± 8.9 years. Overall, the 280 study patients experienced a total of 113 AREs. Of them, 85 had only one ARE, 28 had two to three and none had more than three AREs. A total of 68 AREs were completely re-versible, 42 were partially reversible while three could not be reversed with treatment. The mean inci-dence of AREs was 40.4%. The incidence was > 45% between 1986 and 1997, decreased to 20.5% between 1998 and 2000 and to 9% between 2001 and 2004. Graft survival rates in patients with and without AREs were respectively 91% and 93% at three years, 82% and 90% at five years and 73% and 83% at 10 years. We found a decrease in the incidence of AREs in recent years in our study patients, and this was related to the introduction of sensitized cross-match and the newer immunosuppressive agents, particularly MMF. Additionally, AREs had a deleterious impact on late graft survival in our study population.

  3. A new molecular approach to the diagnosis of acute rejection

    Chandraker, Anil; Strom, Terry B.

    2013-01-01

    Renal biopsy is the gold standard for detection of rejection in kidney transplant recipients but is not considered until evidence of renal dysfunction is apparent. Now, Suthanthiran and colleagues suggest that mRNA levels in urinary cells from these patients might be diagnostic and prognostic of acute cellular rejection.

  4. Acute kidney injury after pediatric cardiac surgery

    Sarvesh Pal Singh

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article.

  5. [Acute cardiac failure in pheochromocytoma.

    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...... in left ventricular function and elevated myocardial enzymes. No coronary stenoses were found. The myocardium regained nearly normal systolic function in one and a half month. A renal P was laparoscopicaly removed. We discuss the pathophysiology of catecholamine cardiomyopathy. Udgivelsesdato: 2008...

  6. Early diagnosis of acute postoperative renal transplant rejection

    A prospective evaluation of In-111 labeled autologous platelet scintigraphy for the early diagnosis of acute postoperative renal transplant rejection was undertaken. To date, 28 consecutive patients between 7 and 14 days post-op have been injected with 500μCi of In-111 platelets followed by imaging at 24 and 48 hours. Activity within the renal transplant exceeding activity in the adjacent iliac vessels was considered to be evidence of rejection, and both chemical evidence and clinical impression of rejection at 5 days after completion of imaging was accepted as proof of ongoing or incipient rejection at the time of scintigraphy. In addition, to visual inspection, independent quantitative analysis compared the area-normalized activity over the transplant with the adjacent iliac vessels (normal <1.0). For 5 patients, positive In-111 scintigraphy was present before convincing clinical evidence of rejection. In-111 platelet scintigraphy is useful not only to confirm the clinical diagnosis of rejection but also to establish the early, pre-clinical diagnosis of incipient acute postoperative renal transplant rejection

  7. Early diagnosis of acute postoperative renal transplant rejection

    Tisdale, P.L.; Collier, B.D.; Kauffman, H.M.; Adams, M.B.; Isitman, A.T.; Hellman, R.S.; Rao, S.A.; Joestgen, T.; Krohn, L.

    1985-05-01

    A prospective evaluation of In-111 labeled autologous platelet scintigraphy for the early diagnosis of acute postoperative renal transplant rejection was undertaken. To date, 28 consecutive patients between 7 and 14 days post-op have been injected with 500..mu..Ci of In-111 platelets followed by imaging at 24 and 48 hours. Activity within the renal transplant exceeding activity in the adjacent iliac vessels was considered to be evidence of rejection, and both chemical evidence and clinical impression of rejection at 5 days after completion of imaging was accepted as proof of ongoing or incipient rejection at the time of scintigraphy. In addition, to visual inspection, independent quantitative analysis compared the area-normalized activity over the transplant with the adjacent iliac vessels (normal <1.0). For 5 patients, positive In-111 scintigraphy was present before convincing clinical evidence of rejection. In-111 platelet scintigraphy is useful not only to confirm the clinical diagnosis of rejection but also to establish the early, pre-clinical diagnosis of incipient acute postoperative renal transplant rejection.

  8. Acute renal transplant rejections: A single center experience

    Jabur Wael

    2008-01-01

    Full Text Available We undertook this observational study to assess the incidence of acute rejections (AR in the first six months after transplantation at Al-Karama Hospital, Iraq. Sixty eight patients (49 males and 19 females underwent renal transplantation in 2006 and were followed up weekly. Forty six received kidneys from related donors and 22 from unrelated donors. During the first six months after transplantation AR occurred in 16 patients (23%; 11 (23% related and 5 (23% unrelated donor transplantation. We conclude that the incidence of acute rejection was similar in related and unrelated donor transplantation and the general incidence was comparable to that reported from most centers.

  9. Noninvasive detection of human cardiac transplant rejection with indium-111 antimyosin (Fab) imaging

    Diagnosis of rejection after cardiac transplantation is currently made by right ventricular endomyocardial biopsy. To evaluate antimyosin imaging as a noninvasive means of detecting human cardiac rejection, the Fab fragment of murine monoclonal antimyosin antibodies was labeled with indium-111 and given intravenously to 18 patients (age 45 +/- 12 years) in 20 studies 7 days to 9 years after transplantation. Endomyocardial biopsy specimens were obtained at the time of each imaging study. Eight patients had positive scans confirmed by biopsy as rejection, and eight patients had negative scans and no evidence of rejection on biopsy. Discordance was observed in four studies, two with positive scans and no rejection on biopsy and two with negative scans and positive biopsy. The sensitivity, specificity, and overall accuracy of the technique were each 80%. Imaging with radiolabeled antimyosin antibody Fab fragments may be of value in the noninvasive identification of rejection in the cardiac transplant recipient

  10. Noninvasive detection of human cardiac transplant rejection with indium-111 antimyosin (Fab) imaging

    Frist, W.; Yasuda, T.; Segall, G.; Khaw, B.A.; Strauss, H.W.; Gold, H.; Stinson, E.; Oyer, P.; Baldwin, J.; Billingham, M.

    1987-11-01

    Diagnosis of rejection after cardiac transplantation is currently made by right ventricular endomyocardial biopsy. To evaluate antimyosin imaging as a noninvasive means of detecting human cardiac rejection, the Fab fragment of murine monoclonal antimyosin antibodies was labeled with indium-111 and given intravenously to 18 patients (age 45 +/- 12 years) in 20 studies 7 days to 9 years after transplantation. Endomyocardial biopsy specimens were obtained at the time of each imaging study. Eight patients had positive scans confirmed by biopsy as rejection, and eight patients had negative scans and no evidence of rejection on biopsy. Discordance was observed in four studies, two with positive scans and no rejection on biopsy and two with negative scans and positive biopsy. The sensitivity, specificity, and overall accuracy of the technique were each 80%. Imaging with radiolabeled antimyosin antibody Fab fragments may be of value in the noninvasive identification of rejection in the cardiac transplant recipient.

  11. Computational Chemical Imaging for Cardiovascular Pathology: Chemical Microscopic Imaging Accurately Determines Cardiac Transplant Rejection

    Tiwari, Saumya; Reddy, Vijaya B.; Bhargava, Rohit; Raman, Jaishankar

    2015-01-01

    Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a st...

  12. Acute cardiac failure in neuroleptic malignant syndrome.

    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.

  13. Acute leukaemoid reaction following cardiac surgery

    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.

  14. Shotgun Proteomics Identifies Proteins Specific for Acute Renal Transplant Rejection

    Sigdel, Tara K.; Kaushal, Amit; Gritsenko, Marina; Norbeck, Angela D.; Qian, Wei-Jun; Xiao, Wenzhong; Camp, David G., II; Smith, Richard D.; Sarwal, Minnie M.

    2010-01-01

    Acute rejection (AR) remains the primary risk factor for renal transplant outcome; development of non-invasive diagnostic biomarkers for AR is an unmet need. We used shotgun proteomics applying LC-MS/MS and ELISA to analyze a set of 92urine samples, from patients with AR, stable grafts (STA), proteinuria (NS), and healthy controls (HC). A total of 1446 urinary proteins were identified along with a number of NS specific, renal transplantation specific and AR specific proteins. Relative abundan...

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

    O.C.K.M. Penn

    1979-01-01

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

  16. Radiation therapy treatment of acute refractory renal allograft rejection

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

  17. Late-onset acute rejection after living donor liver transplantation

    Nobuhisa Akamatsu; Yasuhiko Sugawara; Sumihito Tamura; Junichi Keneko; Yuichi Matsui; Kiyoshi Hasegawa; Masatoshi Makuuchi

    2006-01-01

    AIM: To investigate the incidence and risk factors of late-onset acute rejection (LAR) and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids.METHODS: Adult living donor liver transplantation recipients (n = 204) who survived more than 6 mo after living donor liver transplantation were enrolled.Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation,tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration.Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median followup period was 34 mo.RESULTS: LAR was observed in 15 cases (7%) and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset posttransplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients (19%). Multivariate analysis revealed that a cyclosporinebased regimen was significantly associated with LAR.CONCLUSION: Both LAR and drug-induced adverse events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.

  18. Simkania negevensis and acute cellular rejection in lung transplant recipients.

    Jamal, Alainna J; Resende, Mariangela R; Prochnow, Taisa; McGilvray, Ian; Pilewski, Joseph M; Crespo, Maria M; Singer, Lianne G; McCurry, Kenneth R; Kolls, Jay K; Keshavjee, Shaf; Liles, W Conrad; Husain, Shahid

    2015-08-01

    Simkania negevensis infection has been hypothesized to play a role in lung transplant rejection. The incidence of S. negevensis infection and its association with acute cellular rejection (ACR) were determined in a prospective cohort study of 78 lung transplant recipients (LTRs) in Toronto, Canada, and Pittsburgh, USA, from July 2007 to January 2010. Simkania negevensis testing was detected by quantitative polymerase chain reaction (PCR) on bronchoalveolar lavage fluid. The relationship between S. negevensis and ACR was examined using Cox proportional hazards models and generalized linear and latent mixed models. Cumulative incidence estimates for time-to-ACR in S. negevensis PCR-positive vs. PCR-negative LTRs were 52.7% vs. 31.1% at six months and 68.9% vs. 44.6% at one yr, respectively. Although not statistically significant, there was a trend toward a higher risk of ACR among S. negevensis PCR-positive vs. PCR-negative LTRs in all statistical models. PMID:26009941

  19. Clinical and pathological analysis of acute rejection following orthotopic liver transplantation

    MA Yi; WANG Guo-dong; HE Xiao-shun; LI Jun-liang; ZHU Xiao-feng; HU Rui-de

    2009-01-01

    Background Acute rejection is one of the most important factors for prognosis following liver transplantation. With the use of potent immunosuppressants, acute rejection does not always present typical manifestations. Moreover, other complications often occur concomitantly after liver transplantation, which makes early diagnosis of acute rejection more difficult. Acute rejection is best diagnosed by liver biopsy. Differentiation of clinical manifestations and pathological features plays an important role in achieving individualized immunosuppressive treatment and prolonging long term survival of patients given orthotopic liver transplants.Methods From January 2004 to December 2006, 516 orthotopic liver transplantations were performed at the First Affiliated Hospital, Sun Yat-sen University. For patients who suffered acute rejection, clinical manifestations, histopathological features, diagnosis and anti-rejection treatment were summarized and analyzed. Results In 86 cases (16.7%), of the 516 recipients, 106 episodes of acute rejection occurred, which included 9 with histopathological borderline changes, 36 Banff Ⅰ rejections, 48 Banff Ⅱ and 13 Banff Ⅲ. Among these, 36 were cured by adjusting the dose of immunosuppressant and 65 were reversed by methylprednisolone pulse treatment. Five were methylprednisolone resistant, 3 of whom were given OKT3 treatment and 2 underwent liver retransplantation. Conclusions Due to potent immunosuppressive agents, acute rejection following an orthotopic liver transplantation lacks typical clinical manifestations and pathological features. Acute rejection is best diagnosed by liver biopsy. Designing rational individualized immunosuppressive regimen based on clinical and pathological features of acute rejection plays an important role in prolonging long term survival of patients.

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

    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

  1. Outcome of Acute Graft Rejection Associated with Hemodynamic Compromise in Pediatric Heart Transplant Recipients

    Phelps, Christina M.; Tissot, Cecile; Buckvold, Shannon; Gralla, Jane; Ivy, D. Dunbar; Pietra, Biagio A.; Miyamoto, Shelley D.

    2010-01-01

    We sought to analyze the outcome of hemodynamically significant acute graft rejection in pediatric heart transplant recipients from a single-center experience. Acute graft rejection remains a major cause of morbidity and mortality for patients who undergo orthotopic heart transplantation and has been associated with the severity of the rejection episode. A retrospective review of all children experiencing a hemodynamically significant rejection episode after orthotopic heart transplantation w...

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

    A. O. Shevchenko; I. U. Tunjaieva; A. A. Nasyrova; B. L. Mironkov; I. M. Ilinsky; N. P. Mozhejko; I. I. Muminov; O. P. Shevchenko

    2015-01-01

    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 ...

  3. Peer Rejection Cues Induce Cardiac Slowing after Transition into Adolescence

    Gunther Moor, Bregtje; Bos, Marieke G. N.; Crone, Eveline A.; van der Molen, Maurits W.

    2014-01-01

    The present study examined developmental and gender differences in sensitivity to peer rejection across the transition into adolescence by examining beat-by-beat heart rate responses. Children between the ages of 8 and 14 years were presented with unfamiliar faces of age-matched peers and were asked to predict whether they would be liked by the…

  4. Cardiac tamponade in acute rheumatic carditis.

    Tan, A T; Mah, P K; Chia, B L

    1983-01-01

    In patients with valvular heart disease, fever, and cardiomegaly echocardiography is an invaluable noninvasive tool. In this report we describe a young female presenting with cardiac tamponade due to acute rheumatic carditis. Echocardiography showed an exudative pericardial effusion which was haemorrhagic on pericardiocentesis. She responded to steroid therapy with resolution of carditis and pericardial effusion.

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

    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

  6. Identification of cardiac rejection in heterotopic heart transplantation using 111In-antimyosin

    It is important in heart transplantation to evaluate precisely the extent and location of cardiac rejection. At present, right ventricular endomyocardial biopsy has been used as the gold standard, however, establishment of noninvasive, simple, and easy diagnostic procedure is desired. The canine donor heart, in which atrial septal defect and tricuspid regurgitation had been produced beforehand, was heterotopically transplanted into the recipient's chest cavity. In seven dogs, two to three mCi of 111In-antimyosin-Fab was injected intravenously upon cardiac rejection before the heart was excised. 111In-antimyosin myocardial imaging was then performed using a gamma camera. In the same slice, a histopathological rejection score was calculated and divided into mild, moderate or severe injection. The uptake of 111In-antimyosin was significantly higher in moderate and severe rejected myocardium, since this agent produced a specific and selective localization and concentration in areas of myocardial damage. Therefore, this new technique allows the evaluation of therapeutic intervention upon cardiac rejection and may replace right ventricular endomyocardial biopsy. (orig.)

  7. 111-Indium-labelled platelets for diagnosis of acute kidney transplant rejection and monitoring of prostacyclin anti-rejection treatment

    33 patients were examined daily under a gamma camera after weekly injections of 111-In-labelled autologous platelets over a period of at least 4 weeks after transplantation. A group of 33 patients with long-term stable and well-functioning grafts served as controls. By means of a computerized recording technique, platelet trapping in the graft was measured and expressed as platelet-uptake index (PUI). The method worked well for the early diagnosis of acute rejection signified by an increase in PUI, accompanied by a shortening of platelet half life (t/2). 6 patients suffering from acute rejection received infusions of prostacyclin in addition to conventional high-dose methylprednisolone therapy. In 4 cases the PUI decreased again and an improvement in graft function was observed. Prostacyclin infusion treatment was applied also in 12 patients with histologically-proven chronic transplant rejection. Decreased platelet consumption by the graft and a temporary improvement in transplant function were achieved. We suggest that prostacyclin could enrich the possibilities of anti-rejection treatment by providing a tool for the suppression of platelet trapping in the graft. The platelet scan served as a useful method for the early detection of acute rejection, as well as the monitoring of prostacyclin anti-rejection treatment. (Autor)

  8. 111-Indium-labelled platelets for diagnosis of acute kidney transplant rejection and monitoring of prostacyclin anti-rejection treatment

    Leithner, C.; Pohanka, E.; Schwarz, M. (Vienna Univ. (Austria). 2. Medizinische Klinik); Sinzinger, H. (Vienna Univ. (Austria). Abt. fuer Nuklearmedizin); Syre, G. (Vienna Univ. (Austria). Pathologisch-Anatomisches Inst.)

    1984-01-01

    33 patients were examined daily under a gamma camera after weekly injections of 111-In-labelled autologous platelets over a period of at least 4 weeks after transplantation. A group of 33 patients with long-term stable and well-functioning grafts served as controls. By means of a computerized recording technique, platelet trapping in the graft was measured and expressed as platelet-uptake index (PUI). The method worked well for the early diagnosis of acute rejection signified by an increase in PUI, accompanied by a shortening of platelet half life (t/2). 6 patients suffering from acute rejection received infusions of prostacyclin in addition to conventional high-dose methylprednisolone therapy. In 4 cases the PUI decreased again and an improvement in graft function was observed. Prostacyclin infusion treatment was applied also in 12 patients with histologically-proven chronic transplant rejection. Decreased platelet consumption by the graft and a temporary improvement in transplant function were achieved. We suggest that prostacyclin could enrich the possibilities of anti-rejection treatment by providing a tool for the suppression of platelet trapping in the graft. The platelet scan served as a useful method for the early detection of acute rejection, as well as the monitoring of prostacyclin anti-rejection treatment.

  9. Shotgun Proteomics Identifies Proteins Specific for Acute Renal Transplant Rejection

    Sigdel, Tara K.; Kaushal, Amit; Gritsenko, Marina A.; Norbeck, Angela D.; Qian, Weijun; Xiao, Wenzhong; Camp, David G.; Smith, Richard D.; Sarwal, Minnie M.

    2010-01-04

    Acute rejection (AR) remains the primary risk factor for renal transplant outcome; development of non-invasive diagnostic biomarkers for AR is an unmet need. We used shotgun proteomics using LC-MS/MS and ELISA to analyze a set of 92 urine samples, from patients with AR, stable grafts (STA), proteinuria (NS), and healthy controls (HC). A total of 1446 urinary proteins were identified along with a number of NS specific, renal transplantation specific and AR specific proteins. Relative abundance of identified urinary proteins was measured by protein-level spectral counts adopting a weighted fold-change statistic, assigning increased weight for more frequently observed proteins. We have identified alterations in a number of specific urinary proteins in AR, primarily relating to MHC antigens, the complement cascade and extra-cellular matrix proteins. A subset of proteins (UMOD, SERPINF1 and CD44), have been further cross-validated by ELISA in an independent set of urine samples, for significant differences in the abundance of these urinary proteins in AR. This label-free, semi-quantitative approach for sampling the urinary proteome in normal and disease states provides a robust and sensitive method for detection of urinary proteins for serial, non-invasive clinical monitoring for graft rejection after

  10. Chronic cardiac rejection: identification of five upregulated genes in transplanted hearts by differential mRNA display.

    Utans, U; Liang, P; Wyner, L R; Karnovsky, M. J.; Russell, M. E.

    1994-01-01

    Transplant arteriosclerosis, the major manifestation of chronic rejection, develops after allogeneic (Lewis to F344) but not syngeneic (Lewis to Lewis) rat cardiac transplantation. To identify transcriptionally regulated mediators associated with chronic cardiac rejection, we adapted the differential mRNA display technique for in vivo transplant specimens. Gene transcript patterns in four allogeneic hearts showing early signs of chronic rejection were compared with those in two syngeneic hear...

  11. Can deconvolution of renal transplant curves discriminate acute necrosis for acute rejection?

    Full text: The management of allogeneic renal transplants in the acute post-operative period is diagnostically challenging when there is poor or no function of the graft, which occurs in about 10-15% of cases. Although acute tubular necrosis (ATN) is most common, acute transplant rejection remains a possibility in 25% of cases. Radionuclide renography (RRG) allows a non invasive assessment of graft perfusion and function. However, the ability to differentiate ATN from acute rejection, in particular mild cellular type, is quite limited. Thus we sought to improve the diagnostic value of RRG. From a pool of 137 renal transplant recipients from 1997 to 1998, we studied 21 subjects who had had a renal transplant biopsy with a tissue diagnosis of ATN (13) or rejection (8). They were chosen because they had also had serial RRG done at day + 1 and another close to the day of biopsy (day X). For each study, using deconvolution analysis of the input iliac artery bolus as reference, and comparing it with the dispersion of radioactivity over time in the whole graft, which corresponds to the initial iliac artery bolus, we derived a graft delay index (GDI). We then compared the GDIs of day + 1 vs day X, as a simple subtraction and as a linear ratio. In 1 of 13 subjects with ATN, we found that the GDI decreased at day X compared with day + 1. In 7 of 8 with rejection, the GDI increased at day X. Thus by comparing the graft delay index of a study done at some point in the acute post-operative period with day + 1, we can discriminate between ATN and rejection. It is our intention to apply our method in a prospective study

  12. HLA-G Polymorphism (rs16375) and Acute Rejection in Liver Transplant Recipients

    2014-01-01

    Background. HLA-G molecules exhibit immunomodulatory properties that can delay graft rejection. The 14 bp insertion/deletion polymorphism (INDEL) (rs16375) influences the stability of final HLA-G mRNA and its soluble isoforms. Objective. The present study aimed to investigate the possible association between this polymorphism and the incidence of acute rejection in Iranian liver transplant recipients. Methods. Different genotypes were evaluated by PCR. The patients who had acute rejection wit...

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

    Helga Pawelski

    2014-01-01

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

  14. A bedside technique for the diagnosis of acute rejection in renal transplants using 111-In platelets

    A total of 33 patients was studied with the aim of developing a bedside method for providing early diagnosis of acute rejection using 111-In labelled platelets. Platelet deposition was detected in all patients suffering acute rejection. A significant increase in kidney/aortic arch ratio, as measured by the portable bedside system, preceded the clinical diagnosis in 70% of patients. Using this system, it appeared possible not only to diagnose acute rejection at an earlier stage but also to predict irrecoverable transplant loss even in the presence of tubular necrosis. By labelling the platelets repeatedly for at least two weeks after transplantation, the period of highest risk for acute rejection and other complications. The gamma camera should still be employed in the event of markedly increased platelet deposition to differentiate between rejection and vascular complications

  15. Diagnosis of acute cardiac ischemia.

    Pope, J Hector; Selker, Harry P

    2003-02-01

    A better understanding of coronary syndromes allow physicians to appreciate UAP and AMI as part of a continuum of ACI. ACI is a life-threatening condition whose identification can have major economic and therapeutic importance as far as threatening dysrhythmias and preventing or limiting myocardial infarction size. The identification of ACI continues to challenge the skill of even experienced clinicians, yet physicians continue (appropriately) to admit the overwhelming majority of patients with ACI; in the process, they admit many patients without acute ischemia [2], overestimating the likelihood of ischemia in low-risk patients because of magnified concern for this diagnosis for prognostic and therapeutic reasons. Studies of admitting practices from a decade ago have yielded useful clinical information but have shown that neither clinical symptoms nor the ECG could reliably distinguish most patients with ACI from those with other conditions. Most studies have evaluated the accuracy of various technologies for diagnosing ACI, yet only a few have evaluated the clinical impact of routine use. The prehospital 12-lead ECG has moderate sensitivity and specificity for the diagnosis of ACI. It has demonstrated a reduction of the mean time to thrombolysis by 33 minutes and short-term overall mortality in randomized trials. In the general ED setting, only the ACI-TIPI has demonstrated, in a large-scale multicenter clinical trial, a reduction in unnecessary hospitalizations without decreasing the rate of appropriate admission for patients with ACI. The Goldman chest pain protocol has good sensitivity for AMI but was not shown to result in any differences in hospitalization rate, length of stay, or estimated costs in the single clinical impact study performed. The protocol's applicability to patients with UAP has not been evaluated. Single measurement of biomarkers at presentation to the ED has poor sensitivity for AMI, although most biomarkers have high specificity. Serial

  16. Sonographic findings in borderline changes and subclinical acute renal allograft rejection

    Krejci, Karel [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: karel.krejci@fnol.cz; Zadrazil, Josef [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: josef.zadrazil@fnol.cz; Tichy, Tomas [Institute of Pathology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: tomas.tichy@fnol.cz; Al-Jabry, Sadek [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: sadekj@seznam.cz; Horcicka, Vladko [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: vl.horcicka@fnol.cz; Strebl, Pavel [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: apolik@centrum.cz; Bachleda, Petr [2nd Surgical Department and Transplant Centrum, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: petr.bachleda@fnol.cz

    2009-08-15

    Purpose: A clinically manifested acute rejection is associated with graft dysfunction and with some ultrasound findings. The aim of our study was to determine the potential of ultrasound evaluation in the detection of subclinical acute rejective changes diagnosed in stable grafts by protocol biopsy. Methods: Gray-scale evaluation, color Doppler imaging (CDI) and power Doppler imaging (PDI) was performed before each of 184 protocol graft biopsies in 77 patients in the third week, third month and first year after transplantation. The group was divided into four subgroups-normal histological finding, borderline changes, subclinical acute rejection of IA grade, and a clinically manifested acute rejection of IA grade. The sonographic findings were compared with individual groups. Results: Detection of parenchymal edema using gray-scale imaging significantly differentiated borderline changes and subclinical acute rejection of IA grade from normal histological findings in the third week and in the third month (P = 0.013, P = 0.002 and P = 0.024, P < 0.001), respectively. A similar finding could be recorded in the latter group in the first year after transplantation (P = 0.024). The presence of edema and reduced peripheral parenchymal perfusion in PDI significantly more often indicated a clinically manifested acute IA rejection (P = 0.019, P = 0.004, P = 0.044). Parenchymal CDI hyperperfusion had a high specificity (89.5%) but a low sensitivity (60%) in the detection of the subclinical form of acute IA rejection. Conclusion: A composite gray-scale, PDI and CDI evaluation provide a significant differentiation of groups with borderline changes and subclinical acute rejection and groups with normal histological finding and clinically manifested acute rejection.

  17. Non-invasive diagnosis of acute heart- or lung-transplant rejection using radiolabeled annexin V

    Blankenberg, F.G. [Stanford Univ., CA (United States). Dept. of Radiology; Strauss, H.W. [Stanford Univ., CA (United States). Nuclear Medicine Div.

    1999-05-01

    Background. Apoptosis is a ubiquitous set of cellular processes by which superfluous or unwanted cells are eliminated in the body without harming adjacent healthy tissues. When apoptosis is inappropriate (too little or too much), a variety of human diseases can occur, including acute heart or lung transplant rejection. Objective. Our group has developed a new radiopharmaceutical, radiolabeled annexin V, which can image apoptosis. Results and conclusion. Here we briefly review the biomolecular basis of apoptosis and its role in acute rejection. We also describe the possible use of radiolabeled annexin V to screen children noninvasively for acute rejection following organ transplantation. (orig.) With 6 figs., 53 refs.

  18. Non-invasive diagnosis of acute heart- or lung-transplant rejection using radiolabeled annexin V

    Background. Apoptosis is a ubiquitous set of cellular processes by which superfluous or unwanted cells are eliminated in the body without harming adjacent healthy tissues. When apoptosis is inappropriate (too little or too much), a variety of human diseases can occur, including acute heart or lung transplant rejection. Objective. Our group has developed a new radiopharmaceutical, radiolabeled annexin V, which can image apoptosis. Results and conclusion. Here we briefly review the biomolecular basis of apoptosis and its role in acute rejection. We also describe the possible use of radiolabeled annexin V to screen children noninvasively for acute rejection following organ transplantation. (orig.)

  19. Computational Chemical Imaging for Cardiovascular Pathology: Chemical Microscopic Imaging Accurately Determines Cardiac Transplant Rejection

    Tiwari, Saumya; Reddy, Vijaya B.; Bhargava, Rohit; Raman, Jaishankar

    2015-01-01

    Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR) spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients’ biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures. PMID:25932912

  20. Computational chemical imaging for cardiovascular pathology: chemical microscopic imaging accurately determines cardiac transplant rejection.

    Saumya Tiwari

    Full Text Available Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients' biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures.

  1. Cardiac MRI of acute coronary syndrome.

    Akerem Khan, Shamruz; Khan, Shamruz Akarem; Williamson, Eric E; Foley, Thomas A; Cullen, Ethany L; Young, Phillip M; Araoz, Philip A

    2013-05-01

    Acute coronary syndrome (ACS) is a major cause of morbidity and mortality worldwide. New serological biomarkers, such as troponins, have improved the diagnosis of ACS; however, the diagnosis of ACS can still be difficult as there is marked heterogeneity in its presentation and significant overlap with other disorders presenting with chest pain. Evidence is accumulating that cardiac MRI provides information that can aid the detection and differential diagnosis of ACS, guide clinical decision-making and improve risk-stratification after an event. In this review, we present the relevant cardiac MRI techniques that can be used to detect ACS accurately, provide differential diagnosis, identify the sequelae of ACS, and determine prognostication after ACS. PMID:23668741

  2. The Value of Laboratory Diagnostics of Acute Renal Graft Rejection Compared to the Goldstandard Transplant Biopsy

    Fornara, P; Fischer, K; O. Rettkowski; Loertzer, H.; Wicht, A.; L. Kielwagen; Hamza, A.

    2006-01-01

    The main problem of organ transplantation is acute rejection and its therapy. Clinical symptoms (oliguria, hypertension, pain in the transplant, fever, weight gain) and laboratory chemical/histological findings are possible signs of a rejection after kidney transplantation. A suspicion for a rejection is firstly expressed by finding clinical signs. The laboratory chemistry and the histology prove this suspicion true or not. Deviate findings in laboratory chemistry and histology are possible. ...

  3. Impact of Acute Rejection on Kidney Allograft Outcomes in Recipients on Rapid Steroid Withdrawal

    Hamawi, K.; Mazur, M.J.; Mulligan, D. C.; Moss, A. A.; Y. Devarapalli; Chakkera, H.A.; Nijim, S.; R. L. Heilman; Williams, J. W.; Reddy, K.S.

    2011-01-01

    Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW). Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups. Results. 457 kidney transplant recipients tr...

  4. Renography and biopsy-verified acute rejection in renal allotransplanted patients receiving cyclosporin A

    Thomsen, H.S.; Nielsen, S.L.; Larsen, S.; Lokkegaard, H.

    1987-01-01

    Acute impairment of renal function caused by cyclosporin A can be hard to differentiate from acute rejection. Therefore, kidney function after cadaveric allograft transplantation was repeatedly determined by renography in 42 patients receiving either high dose cyclosporin A (32 patients) or azathioprine and prednisone (10 patients) until a graft biopsy showed either acute rejection or no rejection within the first 5 postoperative weeks. The graft function as judged from the renograms was significantly poorer when cyclosporin A was used than when azathioprine and prednisone were the immunosuppressants. In the azathioprine and prednisone group a biopsy showing acute rejection was always preceded by a deterioration in the renogram. In cyclosporin A treated patients a graft biopsy following an early deterioration in the renogram showed acute rejection in only 56% of the biopsies. It was not possible to identify a time course or a function level of the renogram that could predict rejection in these patients. It is concluded that graft biopsies should be used liberally to diagnose rejection during cyclosporin A treatment if surgical complications after transplantations have been ruled out. Radionuclide studies may offer an invaluable aid in determining a nonnephrotoxic initial dose of the drug.

  5. Renography and biopsy-verified acute rejection in renal allotransplanted patients receiving cyclosporin A

    Acute impairment of renal function caused by cyclosporin A can be hard to differentiate from acute rejection. Therefore, kidney function after cadaveric allograft transplantation was repeatedly determined by renography in 42 patients receiving either high dose cyclosporin A (32 patients) or azathioprine and prednisone (10 patients) until a graft biopsy showed either acute rejection or no rejection within the first 5 postoperative weeks. The graft function as judged from the renograms was significantly poorer when cyclosporin A was used than when azathioprine and prednisone were the immunosuppressants. In the azathioprine and prednisone group a biopsy showing acute rejection was always preceded by a deterioration in the renogram. In cyclosporin A treated patients a graft biopsy following an early deterioration in the renogram showed acute rejection in only 56% of the biopsies. It was not possible to identify a time course or a function level of the renogram that could predict rejection in these patients. It is concluded that graft biopsies should be used liberally to diagnose rejection during cyclosporin A treatment if surgical complications after transplantations have been ruled out. Radionuclide studies may offer an invaluable aid in determining a nonnephrotoxic initial dose of the drug. (orig.)

  6. Pretransplant thymic function predicts acute rejection in antithymocyte globulin-treated renal transplant recipients.

    Bamoulid, Jamal; Courivaud, Cécile; Crepin, Thomas; Carron, Clémence; Gaiffe, Emilie; Roubiou, Caroline; Laheurte, Caroline; Moulin, Bruno; Frimat, Luc; Rieu, Philippe; Mousson, Christiane; Durrbach, Antoine; Heng, Anne-Elisabeth; Rebibou, Jean-Michel; Saas, Philippe; Ducloux, Didier

    2016-05-01

    Lack of clear identification of patients at high risk of acute rejection hampers the ability to individualize immunosuppressive therapy. Here we studied whether thymic function may predict acute rejection in antithymocyte globulin (ATG)-treated renal transplant recipients in 482 patients prospectively studied during the first year post-transplant of which 86 patients experienced acute rejection. Only CD45RA(+)CD31(+)CD4(+) T cell (recent thymic emigrant [RTE]) frequency (RTE%) was marginally associated with acute rejection in the whole population. This T-cell subset accounts for 26% of CD4(+) T cells. Pretransplant RTE% was significantly associated with acute rejection in ATG-treated patients (hazard ratio, 1.04; 95% confidence interval, 1.01-1.08) for each increased percent in RTE/CD4(+) T cells), but not in anti-CD25 monoclonal (αCD25 mAb)-treated patients. Acute rejection was significantly more frequent in ATG-treated patients with high pretransplant RTE% (31.2% vs. 16.4%) or absolute number of RTE/mm(3) (31.7 vs. 16.1). This difference was not found in αCD25 monclonal antibody-treated patients. Highest values of both RTE% (>31%, hazard ratio, 2.50; 95% confidence interval, 1.09-5.74) and RTE/mm(3) (>200/mm(3), hazard ratio, 3.71; 95% confidence interval, 1.59-8.70) were predictive of acute rejection in ATG-treated patients but not in patients having received αCD25 monoclonal antibody). Results were confirmed in a retrospective cohort using T-cell receptor excision circle levels as a marker of thymic function. Thus, pretransplant thymic function predicts acute rejection in ATG-treated patients. PMID:27083287

  7. Molecular Classifiers for Acute Kidney Transplant Rejection in Peripheral Blood by Whole Genome Gene Expression Profiling

    Kurian, S M; Williams, A N; Gelbart, T.; Campbell, D.; Mondala, T. S.; Head, S. R.; Horvath, S; Gaber, L; R. Thompson; Whisenant, T; Lin, W; Langfelder, P; Robison, E. H.; Schaffer, R. L.; Fisher, J S

    2014-01-01

    There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with exce...

  8. Increased T cell glucose uptake reflects acute rejection in lung grafts

    Chen, Delphine L.; Wang, Xingan; Yamamoto, Sumiharu; Carpenter, Danielle; Engle, Jacquelyn T.; Li, Wenjun; Lin, Xue; Kreisel, Daniel; Krupnick, Alexander S.; Huang, Howard J.; Gelman, Andrew E.

    2013-01-01

    Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [18F]fluorodeoxyglucose ([18F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the graft...

  9. Acute Tension Pneumothorax Following Cardiac Herniation after Pneumonectomy

    Daniel Steinmann; Eva Rohr; Andreas Kirschbaum

    2010-01-01

    A tension pneumothorax is one of the main causes of cardiac arrest in the initial postoperative period after thoracic surgery. Tension pneumothorax and cardiac herniation must be taken into account in hemodynamically unstable patients after pneumonectomy. We report an unusual case of successful treatment of acute tension pneumothorax following cardiac herniation and intrathoracic bleeding after pneumonectomy.

  10. Cardiac Arrhythmias and Abnormal Electrocardiograms After Acute Stroke.

    Ruthirago, Doungporn; Julayanont, Parunyou; Tantrachoti, Pakpoom; Kim, Jongyeol; Nugent, Kenneth

    2016-01-01

    Cardiac arrhythmias and electrocardiogram (ECG) abnormalities occur frequently but are often underrecognized after strokes. Acute ischemic and hemorrhagic strokes in some particular area of brain can disrupt central autonomic control of the heart, precipitating cardiac arrhythmias, ECG abnormalities, myocardial injury and sometimes sudden death. Identification of high-risk patients after acute stroke is important to arrange appropriate cardiac monitoring and effective management of arrhythmias, and to prevent cardiac morbidity and mortality. More studies are needed to better clarify pathogenesis, localization of areas associated with arrhythmias and practical management of arrhythmias and abnormal ECGs after acute stroke. PMID:26802767

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

    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/mm3 2-4 months after treatment (p = 0.05). CD8+ lymphocytes also decreased during treatment from 233.2 to 65.8 cells/mm3 (p = 0.003) but rose significantly above normal to 381.3 cells/mm3 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

  12. Value of In-111 antimyosin in the diagnosis of cardiac transplant rejection

    The authors have tested the clinical reliability and utility of 111-In antimyosin (IN-AM) in patients with suspected cardiac transplant rejection and in 20 control patients. They have studied 36 patients within 4 days before or after endomyocardial biopsy (EMB). Single-photon emission CT (SPECT) images were obtained 48 hours after injection. The images were interpreted visually and by calculation of a heart-to-lung ratio (H/L). H/L > 1.6 demonstrated various stages of rejection episodes. In six false-negative studies, four patients were treated with a bolus injection of high-dose steroids before IN-AM injection. Two patients developed human antimouse antibodies (HAMA) after repeated injection. A normalizing in EMB finding always correlated with a decrease in the H/L ratio

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

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

    2015-08-01

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

  14. Doppler sonography in renal transplants; differential diagnosis of normal from acute rejection

    We undertook a combined retrospective and prospective analysis of duplex Doppler examinations performed over a perion of 10 months in order to assess the value of Doppler study(DS)in evaluating renal allograft dysfunction. A total of 110 DS on 82 transplant patients were performed including 79 normal transplants, 29 acute rejections and 2 acute tubular necrosis(ATN). Resistive Index(RI) in 79 normal transplants ranged from 0.44 to 0.7 (Mean;0.59+0.07) in the arcuate artery, and from 0.45 to 0.75(mean;0.61+0.08) in the interlobar artery. RI in 29 cases of acute rejection ranged from 0.61 to 1.0(mean ;0.77+0.10)in the interlobar artery. In ATNRI ranged from 0.59 to 0.63(mean 0.62) in the arcuate artery, and from 0.59 to 0.62(mean 0.61) in the interlobar artery. The RI in acute rejection is significantly higher than that of the normal transplants (p<0.001). With a resistive index greater than 0.8, 100% positive predictive value was obtained for the diagnosis of acute rejection. The value less than 0.7 was unlikely to suggest acute rejection(negative predictive value 92%)

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

    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

  16. Graft irradiation in the treatment of acute rejection of renal transplants: a randomized study

    A randomized study of graft irradiation in the treatment of acute rejection of renal transplants was conducted from 1978 to 1981. Patients developing clinical signs of an acute graft rejection received customary antirejection treatment in the form of intravenous administration of high-dose (1 gm per day) of methylprednisolone. They were at the same time randomized to either receive therapeutic irradiation (175 rad every other day to a total of 525 rad) or sham irradiation. Neither the patient nor the Transplant Service surgeons knew at any time whether the radiation treatment had been given. Eighty-three rejection episodes occurring in 64 grafts were entered into the study. Acute rejection was reversed in 84.5% of grafts in the control and 75% in the treated group. The incidence of recurrent rejection was higher in the treated group (66 vs. 46%) and graft survival was lower (22% vs. 54%). The study failed to demonstrate a beneficial effect of graft irradiation in the treatment of acute renal allograft rejection, when used in conjunction with high dose steriods

  17. Graft irradiation in the treatment of acute rejection of renal transplants: a randomized study

    Pilepich, M.V.; Anderson, C.B.; Etheredge, E.E.; Sicard, G.A.; Melzer, J.S.; Blum, J.

    1982-05-01

    A randomized study of graft irradiation in the treatment of acute rejection of renal transplants was conducted from 1978 to 1981. Patients developing clinical signs of an acute graft rejection received customary antirejection treatment in the form of intravenous administration of high-dose (1 gm per day) of methylprednisolone. They were at the same time randomized to either receive therapeutic irradiation (175 rad every other day to a total of 525 rad) or sham irradiation. Neither the patient nor the Transplant Service surgeons knew at any time whether the radiation treatment had been given. Eighty-three rejection episodes occurring in 64 grafts were entered into the study. Acute rejection was reversed in 84.5% of grafts in the control and 75% in the treated group. The incidence of recurrent rejection was higher in the treated group (66 vs. 46%) and graft survival was lower (22% vs. 54%). The study failed to demonstrate a beneficial effect of graft irradiation in the treatment of acute renal allograft rejection, when used in conjunction with high dose steriods.

  18. Renal Contrast-Enhanced Sonography Findings in a Model of Acute Cellular Allograft Rejection.

    Grabner, A; Kentrup, D; Pawelski, H; Mühlmeister, M; Biermann, C; Edemir, B; Heitplatz, B; Van Marck, V; Bettinger, T; Pavenstädt, H; Schlatter, E; Stypmann, J; Tiemann, K; Reuter, S

    2016-05-01

    Noninvasive methods to diagnose and differentiate acute cellular rejection from acute tubular necrosis or acute calcineurin inhibitor toxicity are still missing. Because T lymphocytes play a decisive role in early states of rejection, we investigated the suitability and feasibility of antibody-mediated contrast-enhanced ultrasound by using microbubbles targeted to CD3(+) , CD4(+) , or CD8(+) T cells in different models of renal disease. In an established rat renal transplantation model, CD3-mediated ultrasound allows the detection of acute rejection as early as on postoperative day 2. Ultrasound signal intensities increased with the severity of inflammation. Further, an early response to therapy could be monitored by using contrast-enhanced sonography. Notably, acute tubular necrosis occurring after ischemia-reperfusion injury as well as acute calcineurin inhibitor toxicity could easily be differentiated. Finally, the quantified ultrasound signal correlated significantly with the number of infiltrating T cells obtained by histology and with CD3 mRNA levels, as well as with chemokine CXCL9, CXCL11, and CCL19 mRNA but not with KIM-1 mRNA expression, thereby representing the severity of graft inflammation but not the degree of kidney injury. In summary, we demonstrate that antibody-mediated contrast-enhanced ultrasound targeting T lymphocytes could be a promising tool for an easy and reproducible assessment of acute rejection after renal transplantation. PMID:26613381

  19. Use of surface-enhanced Raman scattering as a prognostic indicator of acute kidney transplant rejection

    Chi, Jingmao; Zaw, Thet; Cardona, Iliana; Hosnain, Mujtaba; Garg, Neha; Lefkowitz, Heather R.; Tolias, Peter; Du, Henry

    2015-01-01

    We report an early, noninvasive and rapid prognostic method of predicting potential acute kidney dysfunction using surface-enhanced Raman scattering (SERS). Our analysis was performed on urine samples collected prospectively from 58 kidney transplant patients using a He-Ne laser (632.8 nm) as the excitation source. All abnormal kidney function episodes (three acute rejections and two acute kidney failures that were eventually diagnosed independently by clinical biopsy) consistently exhibited ...

  20. Insights from Computational Modeling in Inflammation and Acute Rejection in Limb Transplantation

    Wolfram, Dolores; Starzl, Ravi; Hackl, Hubert; Barclay, Derek; Hautz, Theresa; Zelger, Bettina; Brandacher, Gerald; Lee, W. P. Andrew; Eberhart, Nadine; Vodovotz, Yoram; Pratschke, Johann; Pierer, Gerhard; Schneeberger, Stefan

    2014-01-01

    Acute skin rejection in vascularized composite allotransplantation (VCA) is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplex...

  1. Successful therapy with rituximab of refractory acute humoral renal transplant rejection: a case report.

    Celik, A; Saglam, F; Cavdar, C; Sifil, A; Atila, K; Sarioglu, S; Bora, S; Gulay, H; Camsari, T

    2008-01-01

    Acute humoral rejection (AHR) is generally less responsive to conventional anti-rejection treatment with consequent allograft losses. Therapeutic options include antilymphocyte antibody (ATG), intravenous immunglobulin (IVIG), plasmapheresis, or immunoadsorption with protein A together with intensification of immunsuppression with a tacrolimus/mycophenolate mofetil combination. This report describes a transplant recipient who responded to rituximab therapy as treatment for steroid-, ATG-, IVIG-, and plasmapheresis-resistant AHR. PMID:18261611

  2. Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation

    Priscila Cilene León Bueno de Camargo

    2014-08-01

    Full Text Available Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4. The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients.

  3. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma.

    Spain, L; Higgins, R; Gopalakrishnan, K; Turajlic, S; Gore, M; Larkin, J

    2016-06-01

    Immune checkpoint inhibitors such as ipilimumab and nivolumab improve survival in patients with advanced melanoma and are increasingly available to clinicians for use in the clinic. Their safety in organ transplant recipients is not well defined but published case reports describing treatment with ipilimumab have not been complicated by graft rejection. No cases of anti-programmed cell death protein 1 administration are reported in this group. We describe a case of acute graft rejection in a kidney transplant recipient after treatment with nivolumab, after progression on ipilimumab. Potential factors increasing the risk of graft rejection in this case are discussed, in particular the contribution of nivolumab. PMID:26951628

  4. Outcome of Acute Graft Rejection Associated with Hemodynamic Compromise in Pediatric Heart Transplant Recipients

    Tissot, Cecile; Buckvold, Shannon; Gralla, Jane; Ivy, D. Dunbar; Pietra, Biagio A.; Miyamoto, Shelley D.

    2011-01-01

    We sought to analyze the outcome of hemodynamically significant acute graft rejection in pediatric heart transplant recipients from a single-center experience. Acute graft rejection remains a major cause of morbidity and mortality for patients who undergo orthotopic heart transplantation and has been associated with the severity of the rejection episode. A retrospective review of all children experiencing a hemodynamically significant rejection episode after orthotopic heart transplantation was performed. Fifty-three patients with 54 grafts had 70 rejection episodes requiring intravenous inotropic support. Forty-one percent of these patients required high-dose inotropic support, with the remaining 59% of patients requiring less inotropic support. Overall graft survival to hospital discharge was 41% for patients in the high-dose group compared to 94% in the low-dose group. Six-month graft survival in patients who required high-dose inotropes remained at 41% compared to 44% in the low-dose group. Hemodynamically significant acute graft rejection in pediatric heart transplant recipients is a devastating problem with poor short- and long-term outcomes. Survival to hospital discharge is dismal in patients who require high-dose inotropic support. In contrast, survival to discharge is quite good in patients who require only low-dose inotropic support; however, six-month graft survival in this group is low secondary to a high incidence of graft failure related to worsening or aggressive transplant coronary artery disease. PMID:20963408

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

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

  6. CXCL9 and CXCL10 accelerate acute transplant rejection mediated by alloreactive memory T cells in a mouse retransplantation model

    ZHUANG, JIAWEI; SHAN, ZHONGGUI; MA, TENG; LI, CHUN; QIU, SHUIWEI; ZHOU, XIAOBIAO; LIN, LIANFENG; QI, ZHONGQUAN

    2014-01-01

    C-X-C motif chemokine ligand (CXCL) 9 and CXCL10 play key roles in the initiation and development of acute transplant rejection. Previously, higher levels of RANTES expression and secretion were demonstrated in retransplantation or T-cell memory-transfer models. In the present study, the effect of the chemokines, CXCL9 and CXCL10, were investigated in a mouse retransplantation model. BALB/c mice were used as donors, while C57BL/6 mice were used as recipients. In the experimental groups, a heterotopic heart transplantation was performed six weeks following skin grafting. In the control groups, a heterotopic heart transplantation was performed without skin grafting. Untreated mice served as blank controls. The mean graft survival time of the heterotopic heart transplantations was 7.7 days in the experimental group (n=6), as compared with 3.25 days in the control group (n=6; P<0.001). On day three following cardiac transplantation, histological evaluation of the grafts revealed a higher International Society for Heart & Lung Transplantation grade in the experimental group as compared with the control group. In addition, gene expression and serum concentrations of CXCL9, CXCL10, interferon-γ, and interleukin-2 were markedly higher in the experimental group when compared with the control group. Differences between the levels of CXCL9 and CXCL10 in the pre- and post-transplant mice indicated that the chemokines may serve as possible biomarkers to predict acute rejection. The results of the present study demonstrated that CXCL9 and CXCL10 play a critical role in transplantation and retransplantation. High levels of these cytokines during the pre-transplant period may lead to extensive acute rejection. Thus, the observations enhance the understanding of the mechanism underlying the increased expression and secretion of CXCL9 and CXCL10 by alloreactive memory T cells. PMID:24944628

  7. T cell immunohistochemistry refines lung transplant acute rejection diagnosis and grading

    2013-01-01

    Objective Lung transplant volume has been increasing. However, inaccurate and uncertain diagnosis for lung transplant rejection hurdles long-term outcome due to, in part, interobserver variability in rejection grading. Therefore, a more reliable method to facilitate diagnosing and grading rejection is warranted. Method Rat lung grafts were harvested on day 3, 7, 14 and 28 post transplant for histological and immunohistochemical assessment. No immunosuppressive treatment was administered. We explored the value of interstitial T lymphocytes quantification by immunohistochemistry and compared the role of T cell immunohistochemistry with H&E staining in diagnosing and grading lung transplant rejection. Results Typical acute rejection from grade A1 to A4 was found. Rejection severity was heterogeneously distributed in one-third transplanted lungs (14/40): lesions in apex and center were more augmented than in the base and periphery of the grafts, respectively. Immunohistochemistry showed profound difference in T lymphocyte infiltration among grade A1 to A4 rejections. The coincidence rate of H&E and immunohistochemistry was 77.5%. The amount of interstitial T lymphocyte infiltration increased gradually with the upgrading of rejection. The statistical analysis demonstrated that the difference in the amount of interstitial T lymphocytes between grade A2 and A3 was not obvious. However, T lymphocytes in lung tissue of grade A4 were significantly more abundant than in other grades. Conclusions Rejection severity was heterogeneously distributed within lung grafts. Immunohistochemistry improves the sensitivity and specificity of rejection diagnosis, and interstitial T lymphocyte quantitation has potential value in diagnosing and monitoring lung allograft rejection. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1536075282108217. PMID:24330571

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

    张国伟; 刘宏宇; 夏求明; 李君权; 吕航; 张庆华; 姚志发

    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.

  9. Cardiac computed tomography in patients with acute coronary syndrome

    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.

  10. Efficacy of mycofenolate mofetil for steroid-resistant acute rejection after living donor liver transplantation

    Nobuhisa Akamatsu; Yasuhiko Sugawara; Sumihito Tamura; Yuichi Matsui; Junichi Kaneko; Masatoshi Makuuchi

    2006-01-01

    AIM: To discuss the use of mycophenolate mofetil (MMF) as an immunosuppressant in steroid resistant rejection after liver transplantation. METHODS: The clinical records of 260 adult patients who underwent living donor liver transplantation (LDLT) were reviewed. Tacrolimus and methylprednisolone were used for primary immunosuppression. Acute rejection was first treated with steroids. When steroid resistance occurred, the patient was treated with a combination of steroids and MMF. Anti-T-cell monoclonal antibody was administered to patients who were not responsive to steroids in combination with MMF.RESULTS: A total of 90 (35%) patients developed acute rejection. The median interval time from transplantation to the first episode was 15 d. Fifty-four patients were steroid resistant. Forty-four patients were treated with MMF and the remaining 10 required anti-T-cell monoclonal antibody treatment. Progression to chronic rejection was observed in one patient. Bone marrow suppression and gastrointestinal symptoms were the most common side effects associated with MMF use. There was no significant increase in opportunistic infections. CONCLUSION: Our results demonstrate that MMF is a potent and safe immunosuppressive agent for rescue therapy in patients with acute rejection after LDLT.

  11. HLA-G Polymorphism (rs16375) and Acute Rejection in Liver Transplant Recipients

    Azarpira, Negar; Aghdaie, Mahdokht H.; Kazemi, Kurosh; Darai, Masumeh

    2014-01-01

    Background. HLA-G molecules exhibit immunomodulatory properties that can delay graft rejection. The 14 bp insertion/deletion polymorphism (INDEL) (rs16375) influences the stability of final HLA-G mRNA and its soluble isoforms. Objective. The present study aimed to investigate the possible association between this polymorphism and the incidence of acute rejection in Iranian liver transplant recipients. Methods. Different genotypes were evaluated by PCR. The patients who had acute rejection within 6 months after transplantation were classified as acute rejection (AR) group, while others were considered as nonacute rejection (NAR) group. Results. Among the recipients, 21 patients (21%) had at least one episode of AR, while the other 79 patients (79%) had normal liver function. No significant differences were found between the two groups regarding sex, MELD score, and primary liver disease. Also, no difference was observed concerning rs16375 genotype and allele frequency (P = 0.44, OR: 0.69; CI: 0.21–2.10). Conclusion. The study results revealed no significant difference between the AR and the NAR groups regarding the 14 bp INDEL genotypes and alleles. Further studies are recommended to be conducted on other polymorphic sites as well as monitoring of serum HLA-G concentration in order to ascertain the potential implications of this marker in our population. PMID:24591768

  12. Perfusatory recovery of the grafted lung during convalescence from acute rejection.

    Yamamoto, H; Okada, M; Tobe, S; Tsuji, F; Ohbo, H; Yamashita, C

    2000-01-01

    The aim of this study was to evaluate whether or not perfusatory recovery of the grafted lung occurs is the early stage of convalesce from acute rejection following a single lung transplantation. Eight adult mongrel dogs underwent an allotransplantation of the left lung with treatment of 10 mg/kg cyclosporine and 4 mg/kg azathioprine. Doppler flow probes were placed to the ascending aorta and the left pulmonary artery. Immunosuppressant therapy was discontinued to induce rejection after postoperative day 14. When the left pulmonary artery flow rate (l-PAFR) decreased to less than 20%, methylprednisolone (20 mg/kg) was administered for 3 days along with a resumption of cyclosporine and azathioprine. Pulmonary circulation and chest roentgenograms were evaluated every day through the rejection episode. An open lung biopsy was also performed in each dog to obtain specimens of the grafts and native lungs for histologic examination. When l-PAFR decreased to less than 20%, mild acute rejection was found in all dogs. l-PAFR increased significantly on the third day after methylprednisolone treatment. Thereafter, a histologic examination revealed minimal acute rejection in one dog and no abnormality in seven dogs. The perfusatory recovery of the grafted lung was thought to reflect the histological change in the course of convalescence. PMID:10664339

  13. Usefulness of liver stiffness measurement during acute cellular rejection in liver transplantation.

    Crespo, Gonzalo; Castro-Narro, Graciela; García-Juárez, Ignacio; Benítez, Carlos; Ruiz, Pablo; Sastre, Lydia; Colmenero, Jordi; Miquel, Rosa; Sánchez-Fueyo, Alberto; Forns, Xavier; Navasa, Miquel

    2016-03-01

    Liver stiffness measurement (LSM) is a useful method to estimate liver fibrosis and portal hypertension. The inflammatory process that takes place in post-liver transplant acute cellular rejection (ACR) may also increase liver stiffness. We aimed to explore the association between liver stiffness and the severity of ACR, as well as to assess the relationship between liver stiffness and response to rejection treatment in a prospective study that included 27 liver recipients with biopsy-proven ACR, 30 stable recipients with normal liver tests, and 30 hepatitis C virus (HCV)-infected LT recipients with histologically diagnosed HCV recurrence. Patients with rejection were stratified into 2 groups (mild and moderate/severe) according to the severity of rejection evaluated with the Banff score. Routine biomarkers and LSM with FibroScan were performed at the time of liver biopsy (baseline) and at 7, 30, and 90 days in patients with rejection and at baseline in control patients. Median baseline liver stiffness was 5.9 kPa in the mild rejection group, 11 kPa in the moderate/severe group (P = 0.001), 4.2 kPa in stable recipients (P = 0.02 versus mild rejection), and 13.6 kPa in patients with recurrent HCV (P = 0.17 versus moderate/severe rejection). The area under the receiver operator characteristic curve of LSM to discriminate mild versus moderate/severe ACR was 0.924, and a LSM value of 8.5 kPa yielded a positive predictive value of 100% to diagnose moderate/severe rejection. Liver stiffness improved in 7%, 21%, and 64% of patients with moderate/severe rejection at 7, 30, and 90 days. In conclusion, according to the results of this exploratory study, LSM is associated with the severity of ACR in liver transplantation and thus may be of help in its assessment. Liver Transpl 22:298-304, 2016. © 2015 AASLD. PMID:26609794

  14. Harmful Effect of Anti-Class II Antibodies in Kidney Transplant Patients who Experienced an Acute Rejection Episode

    Berthou, F.; Absi, L.; Mariat, C; Alamartine, E.; M. Phayphet

    2006-01-01

    The presence of anti-lymphocytes antibodies is associated with the occurrence of acute rejection after kidney transplantation but few is known on their role after the rejection episode. We conducted a retrospective study in kidney transplant recipients who experienced a biopsy proven acute rejection episode to analyse the influence of anti-lymphocytes antibodies on clinical outcome. Anti-lymphocytes antibodies were detected before and after transplantation and characterized for isotype, class...

  15. Variation of T cell subset during acute rejection after liver transplantation in rhesus monkeys

    Ran Jiang-hua; Liu Jing; Zhang Xi-bing; Zhang Sheng-ning; Wu Shu-yuan; Li Lai-bang; Li Wang; Li Li

    2014-01-01

    Abstract BACKGROUND: Looking for the early diagnosis of acute rejection indicators after liver transplantation can assess the risk after liver transplantation quickly and effectively, and T lymphocytes play the significant role in acute rejection. OBJECTIVE:To observe the relationship between acute rejection and variation of expression of T cel subset in blood after liver transplantation in rhesus monkey. METHODS: The sixteen liver transplant models in rhesus monkey which were constructed successfuly by the method of “double-cuff and one support tube” were divided into two groups randomly: experiment group (no treated by immunosuppressant in perioperative period) and control group (treated by immunosuppressant in perioperative period). Then the blood specimen and liver tissue respectively were colected at 6, 12, 24 and 72 hours after operation. The levels of alanine transferase, aspartate aminotransferase, and total bilirubin were detected with the fuly automatic biochemical analyser. The levels of CD4+/CD8+were tested by flow cytometry. The liver tissue in rhesus monkey after liver transplantation was detected by hematoxylin-eosin staining. The degree of acute rejection was evaluated by Banff Score System. RESULTS AND CONCLUSION: Acute rejection appeared in the experiment group at 12, 24, and 72 hours after liver transplantation. Levels of alanine transferase, aspartate aminotransferase, and total bilirubin were significantly higher in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). The expression of CD4+/CD8+of the experiment group and control group began to rise at 6 hours after surgery, but the experiment group increased the most obvious. CD4+/CD8+ expression was significantly greater in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). Morphological pathology was severer, and Banff score was higher in the experiment group than in the control group at

  16. Use of surface-enhanced Raman scattering as a prognostic indicator of acute kidney transplant rejection

    Chi, Jingmao; Zaw, Thet; Cardona, Iliana; Hosnain, Mujtaba; Garg, Neha; Lefkowitz, Heather R.; Tolias, Peter; Du, Henry

    2015-01-01

    We report an early, noninvasive and rapid prognostic method of predicting potential acute kidney dysfunction using surface-enhanced Raman scattering (SERS). Our analysis was performed on urine samples collected prospectively from 58 kidney transplant patients using a He-Ne laser (632.8 nm) as the excitation source. All abnormal kidney function episodes (three acute rejections and two acute kidney failures that were eventually diagnosed independently by clinical biopsy) consistently exhibited unique SERS spectral features in just one day following the transplant surgery. These results suggested that SERS analysis provides an early and more specific indication to kidney function than the clinically used biomarker, serum creatinine (sCr). PMID:25798301

  17. Lymphotactin: a key regulator of lymphocyte trafficking during acute graft rejection.

    Wang, J D; Nonomura, N; Takahara, S; Li, B S; Azuma, H; Ichimaru, N; Kokado, Y; Matsumiya, K; Miki, T; Suzuki, S; Okuyama, A

    1998-09-01

    The attraction of leucocytes to allografts is essential for rejection. The process is controlled by chemokines. In order to clarify the role of lymphotactin (a cytokine that represents a novel branch of the chemokine superfamily) in regulating leucocyte trafficking during graft rejection, we used rat renal transplantation models to examine its gene expression and the distribution of lymphotactin-expressing cells in renal grafts. Lymphotactin mRNA was upregulated strongly in acutely rejecting renal allografts. The mRNA was undetectable in isografts, chronically rejecting renal allografts or normal kidney. Once lymphotactin was expressed, large numbers of infiltrating lymphocytes were seen. Moreover extended studies demonstrated that in cultured rat spleen cells the expression of lymphotactin mRNA was markedly induced by phytohaemagglutinin (PHA) or phorbol myristate acetate (PMA), and such induction was inhibited by the immunosuppressive drugs FK506 and cyclosporin. Collectively, these observations provide new evidence demonstrating that lymphotactin is a key regulator of lymphocyte motility and adhesiveness during acute allograft rejection. FK506 and cyclosporin inhibition of lymphotactin expression is likely to represent an important molecular mechanism of the action of the drugs. PMID:9767457

  18. Pulmonary circulatory parameters as indices for the early detection of acute rejection after single lung transplantation.

    Yamamoto, H; Okada, M; Tobe, S; Tsuji, F; Ohbo, H; Nakamura, H; Yamashita, C

    1998-01-01

    We investigated the relationship between the changes in the pulmonary blood flow and histology during acute rejection following single lung transplantation. In single lung transplantation using adult mongrel dogs, immunosuppression with cyclosporine and azathioprine was discontinued after postoperative day 14 to induce rejection. Doppler flow probes were placed adjacent to the ascending aorta and the left pulmonary artery to measure the blood flow on a daily basis. In addition, chest roentgenograms were also examined daily. The pulmonary pressure was measured using a Swan-Ganz catheter prior to and following the induction of rejection. Open lung biopsies were performed when the left pulmonary artery flow decreased to half of the prerejection value. The pulmonary artery flow decreased to 14.3% of the aortic flow 5 days after the discontinuation of immunosuppression. The graft pulmonary vascular resistance increased significantly compared to the prerejection values (P < 0.001). This was not accompanied by any abnormalities on chest roentgenography. The histology was consistent, with marked perivascular lymphocytic infiltration with little alveolar or interstitial changes. During rejection, the increased pulmonary vascular resistance in the graft was probably the result of perivascular inflammatory cell infiltration, which was seen prior to changes on chest roentgenography. Changes in the left pulmonary artery flow and histology thus appear to be closely correlated in the early stages of acute rejection. PMID:9744398

  19. Acute or chronic transplant rejection - high resolution CT of the chest in lung transplant recipients

    Purpose: Aim of the study was to evaluate the postoperative changes in patients with single (SLTX) or double lung transplantation (DLTX) with HRCT and to correlate those findings with the clinical diagnosis. Material and methods: 29 patients with SLTX (n = 14) or DLTX (n = 15) were observed for more than 6 years after transplantation by HRCT (n = 82). CT examinations were performed in inspiration and expiration (n = 70) with a slice thickness of 1 mm and a feed of 10 mm. The image material was evaluated by 2 experienced radiologists in consensus. Criteria for acute rejection at HRCT were: ground glass opacities and focal air trapping in expiration. Criteria for chronic transplant rejection were: bronchial dilatation, bronchial wall thickening and thickening of interlobar septae. The clinical evaluation consisted of laboratory tests, lung function tests, and bronchoscopy including bronchial lavage in special cases. Results: 20/29 patients are still alive (mean 21 months). 5/9 patients died because of chronic transplantant rejection, 1 patient suffered from a non-Hodgkin's lymphoma localised at the right hilus. Severe threatening pneumonia occurred in 13 cases. 10/29 patients showed symptoms of acute rejection. Expiratory HRCT found a focal air trapping in all cases and extended ground glass opacities in 11/14 cases. Also a bronchial dilatation was observed in more than 50% (9/14). 12/29 patients suffered from chronic transplant rejection. HRCT showed bronchial dilatation in 26/27 investigations and severe ground glass opacities in 21/27 investigations. Thickening of the interlobal septa as well as centrilobular opacities were found in more than 50% of the examinations. Conclusion: High resolution CT of the chest in patients after lung transplantation is able to show numerous pathological alterations. Without clinical information a confident differentiation in acute or chronic transplant rejection or pneumonia can be difficult or impossible. (orig.)

  20. Haptoglobin activates innate immunity to enhance acute transplant rejection in mice

    Shen, Hua; Song, Yang; Colangelo, Christopher M.; Wu, Terence; Bruce, Can; Scabia, Gaia; Galan, Anjela; Maffei, Margherita; Goldstein, Daniel R.

    2011-01-01

    Immune tolerance to transplanted organs is impaired when the innate immune system is activated in response to the tissue necrosis that occurs during harvesting and implantation procedures. A key molecule in this immune pathway is the intracellular TLR signal adaptor known as myeloid differentiation primary response gene 88 (MyD88). After transplantation, MyD88 induces DC maturation as well as the production of inflammatory mediators, such as IL-6 and TNF-α. However, upstream activators of MyD88 function in response to transplantation have not been identified. Here, we show that haptoglobin, an acute phase protein, is an initiator of this MyD88-dependent inflammatory process in a mouse model of skin transplantation. Necrotic lysates from transplanted skin elicited higher inflammatory responses in DCs than did nontransplanted lysates, suggesting DC-mediated responses are triggered by factors released during transplantation. Analysis of transplanted lysates identified haptoglobin as one of the proteins upregulated during transplantation. Expression of donor haptoglobin enhanced the onset of acute skin transplant rejection, whereas haptoglobin-deficient skin grafts showed delayed acute rejection and antidonor T cell priming in a MyD88-dependent graft rejection model. Thus, our results show that haptoglobin release following skin necrosis contributes to accelerated transplant rejection, with potential implications for the development of localized immunosuppressive therapies. PMID:22156194

  1. Incidence and Severity of Acute Allograft Rejection in Liver Transplant Recipients Treated With Alfa lnterferon

    Jain, Ashokkumar; Demetris, Anthony J.; Manez, Rafael; Tsamanadas, Athanassisos C.; Thiel, David; Rakela, Jorge; Starzl, Thomas E.; Fung, John J.

    1998-01-01

    Interferon alfa-2b (IFN-α) therapy has been shown to be effective in the treatment of viral hepatitis B (HBV) or viral hepatitis C (HCV) in patients who did not undergo transplantation. However, in allograft recipients, treatment with IFN-α often leads to allograft rejection. The aim of the present study was to determine if IFN-α therapy increases the incidence or severity of acute rejection in human liver allograft recipients. One hundred five orthotopic liver transplant (OLT) recipients wit...

  2. New scoring system identifies kidney outcome with radiation therapy in acute renal allograft rejection

    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

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

    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.

  4. Renal blood flow after transplantation: Effects of acute tubular necrosis, rejection, and cyclosporine toxicity

    The authors incorporated their recently developed radionuclide first pass-technique for the quantitative measurement of renal transplant perfusion into routine DTPA imaging. Using this technique they investigated the effects of acute tubular necrosis (ATN), rejection, and cyclosporing toxicity on renal blood flow in a series of 80 studies in 35 patients, with independent evaluation of renal function. Transplant flow values were as follows: normal functioning, 439 mL/min +-83; ATN 248 mL/min +-63; rejection, 128 mL/min +-58; cyclosporing toxicity, 284 mL/min +-97; (normal flow in nontransplanted kidneys, approximately 550 mL/min). Differences between normal functioning, ATN, and rejection were significant (P < .05). Interestingly, immediate postsurgical hyperemia frequently occurred, with flow values sometimes exceeding 700 mL/min

  5. Infusion of nonmyeloablative bone marrow alleviates acute rejection reaction in liver allotransplantation

    XIE Hai-yang; HUANG Dong-sheng; JIA Chang-ku; ZHENG Shu-sen

    2005-01-01

    Objective: To study the effect and implication of nonmyeloablative donor specific bone marrow (DSBM) infusion on the immunoreaction of liver allotransplantation. Methods: Orthotopic liver transplantation model was used in this study. Groups were set as follows: Group Ⅰ, syngeneic control (Wistar-to-Wistar); Group Ⅱ, acute rejection (SD-to-Wistar); Group Ⅲ, acute rejection treated with cyclosporine A (CsA) by intramuscular injection (SD-to-Wistar+CsA); Group Ⅳ, bone marrow infusion at 7 d pretransplantation followed by short-term CsA treatment (SD-to-Wistar+DSBM); Another group of short-term CsA treatment preoperatively without bone marrow infusion was also set as control. General characteristics and survival time were observed.Histological grades of rejection were determined by pathological examination. IL-2 and IFN-γ level in peripheral blood and donor liver were detected respectively by Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot. Chimerism of donor cells was measured by PCR for a male-specific marker (Y-chromosome-specific sequence, Sry). Results: No signs of rejection were found in Group Ⅰ. Acute rejection occurred in both Group Ⅱ and the short-term CsA treated group. All the recipients died at (9~15)d posttransplantation with a median survival time of (10.7±0.5) d and (11.2±2.4) d, respectively. Only mild rejection could be seen in Group Ⅲ. In Group Ⅳ, 4 out of 6 recipients had long-term survival (>100 d), the histological grade of rejection was significantly lower than that of Group Ⅱ, so did the expression level of IL-2 and IFN-γ in both peripheral blood and grafted liver.Y-chromosome-specific sequence (Sry) of male SD rats could be detected in the bone marrow, spleen and thymus of female recipients at 15 d after bone marrow infusion. Conclusion: Mild preconditioning nonmyeloablative donor specific bone marrow infusion can enhance chimerism formation in recipients, alleviate the rejection of liver allotransplantation

  6. Combined Detection of Serum IL-10, IL-17, and CXCL10 Predicts Acute Rejection Following Adult Liver Transplantation

    Kim, Nayoung; Yoon, Young-In; Yoo, Hyun Ju; Tak, Eunyoung; Ahn, Chul-Soo; Song, Gi-Won; Lee, Sung-Gyu; Hwang, Shin

    2016-01-01

    Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity. PMID:27498551

  7. Pathological and clinical correlates of FOXP3+ cells in renal allografts during acute rejection.

    Veronese, F; Rotman, S; Smith, R N; Pelle, T D; Farrell, M L; Kawai, T; Benedict Cosimi, A; Colvin, R B

    2007-04-01

    The localization and significance of regulatory T cells (Treg) in allograft rejection is of considerable clinical and immunological interest. We analyzed 80 human renal transplant biopsies (including seven donor biopsies) with a double immunohistochemical marker for the Treg transcription factor FOXP3, combined with a second marker for CD4 or CD8. Quantitative FOXP3 cell counts were performed and analyzed for clinical and pathologic correlates. FOXP3(+) cells were present in the interstitium in acute cellular rejection (ACR) type I and II, at a greater density than in acute humoral rejection or CNI toxicity (p attraction or generation at that site. Considering only patients with ACR, a higher density of FOXP3(+) correlated with HLA class II match (p = 0.03), but paradoxically with worse graft survival. We conclude that infiltration of FOXP3(+) cells occurs in ACR to a greater degree than in humoral rejection, however, within the ACR group, no beneficial effect on outcome was evident. Tregs concentrate in tubules, probably contributing to FOXP3 mRNA in urine; the significance and pathogenesis of 'Treg tubulitis' remains to be determined. PMID:17286616

  8. Quantitative study of Indium-111-oxine platelet kinetics in acute and chronic renal transplant rejection

    Heyns, A.duP.; Pieters, H.; Badenhorst, P.N.; Wessels, P.; Loetter, M.G.; Minnaar, P.C.; Pauw, F.H.

    1982-01-01

    Thirteen patients were investigated on 22 occasions at times varying from 1 day to 10 years after living family donor or cadaver renal transplantation. Platelet survival in the circulation, and in vivo platelet distribution and sites of deposition and sequestration was quantitatively determined with Indium-111-oxine (In-111-oxine) labelled platelets and a scintillation camera interfaced with a computer assisted imaging system. In all patients platelet survival was shortened and the platelet survival curve exponential. In patients with no evidence of transplant rejection and those with chronic rejection, there was no measurable or visible accumulation of labelled platelets in the kidney. The sequestration pattern of In-111 labelled platelets at the end of platelet life span was within normal limits and located in the reticuloendothelial system. In those patients with acute transplant rejection, platelet survival was shortened. Labelled platelets accumulated in the kidney: this was clearly visualized on scintigraphy and reflected by a significant increase in the radioactivity count density of the kidney. Platelets not deposited in the transplant were sequestrated in the reticuloendothelial system. This study demonstrates the diagnostic value of In-111 labelled platelet kinetics in the investigation of acute renal failure after renal transplantation. This investigation appears of limited clinical value in chronic rejection.

  9. A quantitative study of Indium-111-oxine platelet kinetics in acute and chronic renal transplant rejection

    Thirteen patients were investigated on 22 occasions at times varying from 1 day to 10 years after living family donor or cadaver renal transplantation. Platelet survival in the circulation, and in vivo platelet distribution and sites of deposition and sequestration was quantitatively determined with Indium-111-oxine (In-111-oxine) labelled platelets and a scintillation camera interfaced with a computer assisted imaging system. In all patients platelet survival was shortened and the platelet survival curve exponential. In patients with no evidence of transplant rejection and those with chronic rejection, there was no measurable or visible accumulation of labelled platelets in the kidney. The sequestration pattern of In-111 labelled platelets at the end of platelet life span was within normal limits and located in the reticuloendothelial system. In those patients with acute transplant rejection, platelet survival was shortened. Labelled platelets accumulated in the kidney: this was clearly visualized on scintigraphy and reflected by a significant increase in the radioactivity count density of the kidney. Platelets not deposited in the transplant were sequestrated in the reticuloendothelial system. This study demonstrates the diagnostic value of In-111 labelled platelet kinetics in the investigation of acute renal failure after renal transplantation. This investigation appears of limited clinical value in chronic rejection. (orig.)

  10. Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration.

    Kueckelhaus, Maximilian; Fischer, Sebastian; Seyda, Midas; Bueno, Ericka M; Aycart, Mario A; Alhefzi, Muayyad; ElKhal, Abdallah; Pomahac, Bohdan; Tullius, Stefan G

    2016-06-01

    The advent of more potent immunosuppressants led to the first successful human upper extremity transplantation in 1998. At this time, >100 upper extremity transplants, 30 face transplants, and a variety of other vascularized composite allotransplantation (VCA) procedures have been performed around the world. VCA recipients present unique challenges for transplantation. The incidence of acute rejection exceeds 80% in hand and face transplantation and is well documented, whereas reports about antibody-mediated rejection and chronic rejection remain scarce. Immunosuppression protocols commonly used at US centers are derived from solid organ transplantation protocols. Novel approaches to minimize rejections in VCA may include improved HLA matching and considerations toward cytomegalovirus infection status. New graft preservation techniques may decrease immunogenicity prior to transplant. Novel monitoring methods such as valid biomarkers, ultrasound biomicroscopy, and sentinel flaps may enable earlier diagnosis of rejection. Cell-based therapies are being explored to achieve immunosuppressive regimen minimization or even tolerance induction. The efficacy of local immunosuppression in clinical VCA remains controversial. In conclusion, although immunosuppressive strategies adapted from SOT have demonstrated good midterm results, focusing on the unique features of VCA grafts may enable additional, more specific treatment strategies in the future and improved long-term graft outcomes. PMID:26265179

  11. Tumor Necrosis Factor Receptor 2: Its Contribution to Acute Cellular Rejection and Clear Cell Renal Carcinoma

    Jun Wang; Al-Lamki, Rafia S.

    2013-01-01

    Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein and one of the two receptors that orchestrate the complex biological functions of tumor necrosis factor (TNF, also designed TNF- α ). Accumulating experimental evidence suggests that TNFR2 plays an important role in renal disorders associated with acute cellular rejection and clear cell renal carcinoma but its exact role in these settings is still not completely understood. This papers reviews the factors that may...

  12. Disseminated Intravascular Coagulation (DIC) Accompanied by Acute Rejection in a Post Renal Transplant Recipient

    Dohi, Kiyohiko; Eto, Takaaki; Ono, Eiji; Fukuda, Yasuhiko; Takenaka, Masaharu; Yahata, Hiroshi; Asahara, Toshimasa; Tabe, Yasuji; Marubayashi, Seiji; Ezaki, Haruo

    1984-01-01

    A kidney transplant recipient with disseminated intravascular coagulation (DIC) accompanied by acute rejection was described. The principal symptome of the patient was massive gross hematuria. She showed thrombocytopenia, marked decrease of fibrinogen and elevation of fibrinogen degradation products (FDP) level. The patient was treated by continuous intravenous heparin infusion (total dose was 85, 800 units), and it was very effective. The symtoms due to DIC were improved on the 9th day after...

  13. Functional evaluation of transplanted kidneys in normal function and acute rejection using BOLD MR imaging

    In this study, we evaluated a large number of subjects using BOLD MRI to provide more information about oxygen metabolism in the normal function of transplanted kidneys and to distinguish acute graft rejection from normal function kidneys. This study included 122 subjects (20 volunteers, 72 patients with normal functioning transplants, and 21 patients with acute rejection), and 9 patients had normal function grafts received examination while grafts dysfunction occurred within 6 months during the follow-up. The R2* (1/s) values in the cortex and medulla as well as the R2* ratio of the medulla to cortex (R2* ratio of M/C) were recorded. The R2* values of the medulla were higher than those of the cortex in the normal function group and the volunteers which have a steep R2* ratio of M/C. All the R2* values in the acute rejection group were lower than those in the normal function grafts group (P 1.1) is an important reason for keeping clinical normal function.

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

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

  15. Acute kidney injury after cardiac arrest

    Tujjar, Omar; Mineo, Giulia; Dell’Anna, Antonio; Poyatos-Robles, Belen; Donadello, Katia; Scolletta, Sabino; Vincent, Jean-Louis; Taccone, Fabio Silvio

    2015-01-01

    Introduction The aim of this study was to evaluate the incidence and determinants of AKI in a large cohort of cardiac arrest patients. Methods We reviewed all patients admitted, for at least 48 hours, to our Dept. of Intensive Care after CA between January 2008 and October 2012. AKI was defined as oligo-anuria (daily urine output

  16. Differentiation of acute untreated rejection from cyclosporine nephrotoxicity and acute tubular necrosis by indium-111 labeled platelet scintigraphy

    The authors have previously reported that unlike normal and nephrotic native kidneys, acutely rejecting kidney transplants show significant platelet uptake by Indium-111 labeled platelet scintigraphy (lPLS). To determine if lLPS can differentiate acute rejection (AR) from cyclosporine (CY) nephrotoxicity and acute tubular necrosis (ATN). The authors studied 5 groups of kidney transplant recipients. Group 1, n=6 (3 on Imuran, 3 on CY, CR=1.4 +- 0.6, mean +- SD) had no evidence for rejection (kidney biopsy in 2). Group 11, n=4(1 on Imuran, 3 on CY, Cr=2.8 +- 1.1) had ATN (biopsy in 2). Group 111, n=3(all on CY, Cr=2.3 +- 1.9) had suspected CY nephrotoxicity:all patients (pts) improved upon withdrawal of CY and biopsies were negative for rejection in 2. Group IV, n=11 (10 on Imuran 1 on CY, CR=5.6 +- 4.1) had acute rejection on biopsy. In group V, n=7 (3 on imuran 4 on CY, Cr=6.1 +- 3.4) pts were treated for rejection for 12 +- 4 days. All pts received Prednisone. The first image was obtained 6 +- 4 hrs after injection of 215 +- 30μ Ci of lN-111 and thereafter 1 to 3 times a day for a maximum of 6 days. Platelet Uptake Index (PUl) was calculated as the ratio of uptake over the transplant against a contralateral reference area. One way analysis of variance was carried out. PUIs from groups I, II, III and V were significantly different from groups IV: 1.1 +- .07 (p<0.004), 1.22 +- .09 (p<0.05), 1.14 +- .05 (p<0.04) and 1.21 +- .07 (p<0.004) versus 1.52 +- .17. The authors conclude that 1) ILP can be used for the diagnosis of untreated AR. 2) Untreated AR can be differentiated from CY nephrotoxicity and ATN

  17. Role of cardiac MRI in acute myocardial infarction

    Erwin Mulia

    2013-02-01

    Full Text Available Mortality in patients with acute myocardial infarction (AMI has decreased significantly and appears to be the result of current reperfusion therapeutic strategies. Reperfusion itself may develop into reperfusion injury. Therefore, management of these patients poses several challenges, such as diagnosing and managing heart failure, identifying persistent or inducible ischaemia, estimating the need for anticoagulation, and assessing overall cardiovascular risk. This case presentation will demonstrate the impact of cardiac magnetic resonance imaging (MRI in the assessment of the pathophysiology of AMI in the current reperfusion era. Cardiac MRI can provide a wide range of clinically useful information which will help clinicians to manage and choose specific therapeutic strategies for AMI patients. (Med J Indones. 2013;22:46-53Keywords: Acute myocardial infarction, cardiac magnetic resonance imaging, reperfusion injury

  18. Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients

    Moes, Dirk Jan A R; Press, Rogier R; Ackaert, Oliver; Ploeger, Bart A; Bemelman, Frederike J; Diack, Cheikh; Wessels, Judith A M; van der Straaten, Tahar; Danhof, Meindert; Sanders, Jan-Stephan F; Homan van der Heide, Jaap J; Guchelaar, Henk Jan; de Fijter, Johan W

    2016-01-01

    AIMS: This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). METHODS: Adult renal transplant recipients (n = 361) on cyclosporine-based

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

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

    2009-06-01

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

  20. Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients

    2012-01-01

    Background Acute rejection (AR) episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Non-invasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population. Methods In this proof of principle study, serial urine samples in the early post transplant phase from 6 patients with biopsy verified acute rejections and 6 age-matched controls without clinical signs of rejection were analyzed by shotgun proteomics. Results Eleven proteins fulfilled predefined criteria for regulation in association with AR. They presented detectable regulation already several days before clinical suspicion of AR (increased plasma creatinine). The regulated proteins could be grouped by their biological function; proteins related to growth and proteins related to immune response. Growth-related proteins (IGFBP7, Vasorin, EGF and Galectin-3-binding protein) were significantly up-regulated in association with AR (P = 0.03) while proteins related to immune response (MASP2, C3, CD59, Ceruloplasmin, PiGR and CD74) tended to be up-regulated ( P = 0.13). Conclusion The use of shotgun proteomics provides a robust and sensitive method for identification of potentially predictive urinary biomarkers of AR. Further validation of the current findings is needed to establish their potential clinical role with regards to clinical AR diagnosis. Trial registration ClinicalTrials.gov number NCT00139009 PMID:23369437

  1. Radioimmunoassay of human cardiac tropomyosin in acute myocardial infarction

    Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac 125I-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)

  2. Perspectives on the value of biomarkers in acute cardiac care and implications for strategic management.

    Kossaify, Antoine; Garcia, Annie; Succar, Sami; Ibrahim, Antoine; Moussallem, Nicolas; Kossaify, Mikhael; Grollier, Gilles

    2013-01-01

    Biomarkers in acute cardiac care are gaining increasing interest given their clinical benefits. This study is a review of the major conditions in acute cardiac care, with a focus on biomarkers for diagnostic and prognostic assessment. Through a PubMed search, 110 relevant articles were selected. The most commonly used cardiac biomarkers (cardiac troponin, natriuretic peptides, and C-reactive protein) are presented first, followed by a description of variable acute cardiac conditions with their relevant biomarkers. In addition to the conventional use of natriuretic peptides, cardiac troponin, and C-reactive protein, other biomarkers are outlined in variable critical conditions that may be related to acute cardiac illness. These include ST2 and chromogranin A in acute dyspnea and acute heart failure, matrix metalloproteinase in acute chest pain, heart-type fatty acid binding protein in acute coronary syndrome, CD40 ligand and interleukin-6 in acute myocardial infarction, blood ammonia and lactate in cardiac arrest, as well as tumor necrosis factor-alpha in atrial fibrillation. Endothelial dysfunction, oxidative stress and inflammation are involved in the physiopathology of most cardiac diseases, whether acute or chronic. In summary, natriuretic peptides, cardiac troponin, C-reactive protein are currently the most relevant biomarkers in acute cardiac care. Point-of-care testing and multi-markers use are essential for prompt diagnostic approach and tailored strategic management. PMID:24046510

  3. Utility of Double Filtration Plasmapheresis in Acute Antibody Mediated Renal Allograft Rejection: Report of Three Cases

    Yalçın SOLAK

    2011-09-01

    Full Text Available Plasmapheresis is an extracorporeal procedure, which is often employed to rapidly lower circulating titers of autoantibodies, immune complexes or toxins. There are two types of plasmapheresis namely, regular plasmapheresis (RPP by centrifugation and membrane filtration, and double filtration plasmapheresis (DFPP which is a special form of membrane filtration in which two membranes called as plasma separator and plasma fractionator are employed to filter macromolecules more selectively. DFPP have several advantages over RP. Despite widespread utilization of DFPP in the setting of ABO blood group incompatible kidney transplantation, there is no report regarding DFPP in patients with antibody mediated acute renal allograft rejection who are good candidates for beneficial effects of DFPP. Here we report three renal transplant recipients in whom DFPP was applied as a component of anti-rejection treatment regimen.

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

    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

  5. Molecular Classifiers for Acute Kidney Transplant Rejection in Peripheral Blood by Whole Genome Gene Expression Profiling

    Kurian, S. M.; Williams, A. N.; Gelbart, T.; Campbell, D.; Mondala, T. S.; Head, S. R.; Horvath, S.; Gaber, L.; Thompson, R.; Whisenant, T.; Lin, W.; Langfelder, P.; Robison, E. H.; Schaffer, R. L.; Fisher, J. S.; Friedewald, J.; Flechner, S. M.; Chan, L. K.; Wiseman, A. C.; Shidban, H.; Mendez, R.; Heilman, R.; Abecassis, M. M.; Marsh, C. L.; Salomon, D. R.

    2015-01-01

    There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction. PMID:24725967

  6. Cardiac Arrest in a Heart Transplant Patient Receiving Dexmedetomidine During Cardiac Catheterization.

    Schwartz, Lawrence Israel; Miyamoto, Shelley D; Stenquist, Scott; Twite, Mark David

    2016-06-01

    Dexmedetomidine is an α-2 agonist with a sedative and cardiopulmonary profile that makes it an attractive anesthetic in pediatric cardiac patients. Cardiac transplant patients may suffer from acute cellular rejection of the cardiac conduction system and, therefore, are at an increased risk of the electrophysiological effect of dexmedetomidine. We present such a patient who had a cardiac arrest while receiving dexmedetomidine during cardiac catheterization. Because acute cellular rejection of the cardiac conduction system is difficult to diagnose, dexmedetomidine should be used with caution in pediatric heart transplant patients. PMID:26721807

  7. Cardiac calcification in acute intermittent porphyria

    Tanmoy Ghatak

    2011-01-01

    Full Text Available Aetiology of pericardial calcifications can be multifactorial. Tuberculosis has been reported as the most common cause. Other known causes include uraemia, asbestosis, post-traumatic or postoperative. We report a rare case of pericardial calcification seen in a patient with established acute intermittent porphyria. A direct causal relationship cannot be established between porphyria and pericardial calcification, but it may be due to deposition of the porphyrin in the pericardium.

  8. Cardiac calcification in acute intermittent porphyria

    Tanmoy Ghatak; Afzal Azim; Arvind K Baronia; Banani Poddar

    2011-01-01

    Aetiology of pericardial calcifications can be multifactorial. Tuberculosis has been reported as the most common cause. Other known causes include uraemia, asbestosis, post-traumatic or postoperative. We report a rare case of pericardial calcification seen in a patient with established acute intermittent porphyria. A direct causal relationship cannot be established between porphyria and pericardial calcification, but it may be due to deposition of the porphyrin in the pericardium.

  9. Cortical perfusion index: A predictor of acute rejection in transplanted kidneys

    The presently available non-invasive methods for the diagnosis of acute rejection crisis (ARC) of renal transplants are not satisfactory. However, the need for such a test is of paramount clinical importance. A prospective study of 74 post-transplantation events in renal allograft recipients was performed. Clinical, surgical exploration and biopsy data were correlated with TC-99m DTPA scintigraphy using the following indices: Global perfusion index (GPI), cortical perfusion index (CPI), medullary perfusion index (MPI), the peak-to-plateau ratio (P/P), iliac artery peak to renal peak time (delta-P) and washout half-time (T1/2). Of the 74 events, 24 were proven to be due to acute rejection crisis (ARC), 13 were of ureteral obstruction, 18 various nephropathies and 19 in stable renal transplant function. The P/P, delta-P and T1/2 were not good predictors of ARC; the sensitivity was 79%, 79% and 80% respectively. The sensitivity of the GPI was 58% and the specificity was 87%. The cortical perfusion index rated better: specificity=84% and sensitivity=87%. However, the best indicator of ARC seemed to be the percent increase in cortical perfusion index over previous values obtained during stable graft function. Thus the sensitivity was found to be 91% and specificity was 96%. The difference between global and cortical perfusion indices reflects shunting of blood for cortex to medulla. This study suggest that the cortical perfusion index (CPI) and the percent increase in CPI can be used to non-invasively diagnose acute renal allograft rejection

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

    Silke Roedder

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

  11. Early diagnosis of acute postoperative renal transplant rejection by indium-111-labeled platelet scintigraphy

    A prospective evaluation of 111In-labeled platelet scintigraphy (IPS) for the early diagnosis of acute postoperative renal transplant rejection (TR) was undertaken. The results of IPS were compared with in vitro biochemical tests, the clinical finding of graft tenderness, and combined [/sup 99m/Tc]DTPA and [131I]orthoiodohippurate scintigraphy. With a sensitivity of 0.93 and a specificity of 0.95, IPS provided otherwise unavailable diagnostic information. Furthermore, postoperative IPS was a good predictor of long-term allograft survival

  12. Early diagnosis of acute postoperative renal transplant rejection by indium-111-labeled platelet scintigraphy

    Tisdale, P.L.; Collier, B.D.; Kauffman, H.M.; Adams, M.B.; Isitman, A.T.; Hellman, R.S.; Hoffmann, R.G.; Rao, S.A.; Joestgen, T.; Krohn, L.

    1986-08-01

    A prospective evaluation of /sup 111/In-labeled platelet scintigraphy (IPS) for the early diagnosis of acute postoperative renal transplant rejection (TR) was undertaken. The results of IPS were compared with in vitro biochemical tests, the clinical finding of graft tenderness, and combined (/sup 99m/Tc)DTPA and (/sup 131/I)orthoiodohippurate scintigraphy. With a sensitivity of 0.93 and a specificity of 0.95, IPS provided otherwise unavailable diagnostic information. Furthermore, postoperative IPS was a good predictor of long-term allograft survival.

  13. CHALLENGES IN TREATMENT OF RENAL GRAFT ACUTE ANTIBODY-MEDIATED REJECTION

    A. I. Sushkov

    2016-01-01

    Full Text Available Diagnostic criteria and treatment protocols for acute antibody-mediated rejection (AMR of kidney allograft remain controversial. We report the case of early severe AMR after primary kidney transplantation. The graft removal was considered in the absence of treatment efficacy and in the presence of systemic infl ammatory response syndrome. However, at surgery the graft looked normal and it was not removed. The repeated treatment course (plasmapheresis, antithymocyte globulin, intravenous immunoglobulin and rituximab was effective. The patient has good and stable graft function in 1 year after transplantation. 

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

    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

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

    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.

  16. Inflammatory cells and activation markers in BAL during acute rejection and infection in lung transplant recipients: a prospective, longitudinal study.

    Riise, G C; Kjellström, C; Ryd, W; Scherstén, H; Nilsson, F; Mårtensson, G; Andersson, B A

    1997-08-01

    Acute rejection of the transplanted lung is a clinical problem, since it decreases graft survival and predisposes the patient to chronic rejection and obliterative bronchiolitis (OB). In an earlier study, we had indications that eosinophil cationic protein (ECP) from activated eosinophils and hyaluronan (HYA) from fibroblasts were associated with acute pulmonary rejection. This prospective longitudinal study was designed to investigate whether molecules from activated inflammatory cells in bronchoalveolar lavage (BAL) fluid could serve as clinically useful diagnostic markers for acute rejection. BAL fluid from 138 bronchoscopies performed in 10 single lung, four bilateral lung and five heart-lung transplant recipients were analysed. Nine patients were studied for a period of more than 1 yr (mean 13.4 months) after surgery. Differential cell counts were made from the BAL fluid. ECP, myeloperoxidase (MPO), HYA and interleukin-8 (IL-8) were used as indirect markers for activation and attraction of eosinophils, neutrophils and fibroblasts, respectively. Fifty four episodes of acute rejection were diagnosed. Two patients developed OB. Nine episodes of bacterial infection, 13 episodes of cytomegalovirus (CMV) pneumonitis, three of Pneumocystis carinii infection and one of respiratory syncytial virus (RSV) infection were diagnosed. The mean levels of ECP, MPO, HYA and IL-8 were all higher during rejection episodes, but differences were not statistically significant compared to no rejection, when the confounding factors of time, concomitant infection, and repeated measures in the same individual had been accounted for. We could not confirm that measurements of eosinophil cationic protein, myeloperoxidase, hyaluronan and interleukin-8 in bronchoalveolar lavage fluid can be used as diagnostic markers for acute rejection in the postoperative follow-up of lung transplant recipients. PMID:9272913

  17. Studies of CTLA4Ig in acute rejection of pancreas transplantation in rats

    Junbo Yu; Zekuan Xu; Shuguang Han; Yi Miao

    2006-01-01

    Objective: To investigate the protective effect of CTLA4Ig in rejection of pancreaticoduodenal transplantation model of rat. Methods: Pancreaticoduodenal transplantion models were established from the donor F344 rats to the Lewis recipients. The models were divided into 2 groups: Group A and B with 12 rats in each group.2 days after transplantation, reciepients in group A were treated with i.p. injection of sailine, and those in group B CTLA4I were injected(200 μg). On day 1,4,7,10after transplantation, the grafts were harvested for histopathological examination. On day 4 after transplantation, the CD4+CD25+Tcells in the grafts were detected by Flow Cytometry. Results: Compared with group A: the degree of the rejection of grafts in group B was lower. The number of CD4+CD25+ T cells of graft was (7.91±1.26)% in group A and (13.81±1.71)% in group B, which had significant difference(P<0.01). Conclusion: CTLA4Ig could inhibit T cell costimulatory pathway, prevent acute rejection, which might be mediated by increasing the number of CD4+CD25+ regulatory T cells.

  18. Comparison of multiplex meta analysis techniques for understanding the acute rejection of solid organ transplants

    Khatri Purvesh

    2010-10-01

    Full Text Available Abstract Background Combining the results of studies using highly parallelized measurements of gene expression such as microarrays and RNAseq offer unique challenges in meta analysis. Motivated by a need for a deeper understanding of organ transplant rejection, we combine the data from five separate studies to compare acute rejection versus stability after solid organ transplantation, and use this data to examine approaches to multiplex meta analysis. Results We demonstrate that a commonly used parametric effect size estimate approach and a commonly used non-parametric method give very different results in prioritizing genes. The parametric method providing a meta effect estimate was superior at ranking genes based on our gold-standard of identifying immune response genes in the transplant rejection datasets. Conclusion Different methods of multiplex analysis can give substantially different results. The method which is best for any given application will likely depend on the particular domain, and it remains for future work to see if any one method is consistently better at identifying important biological signal across gene expression experiments.

  19. Difficulties, guidelines and review of developing an acute rejection model after rat intestinal transplantation.

    Andres, Ane Miren; Santamaria, Monica; Hernandez-Oliveros, Francisco; Guerra, Laura; Lopez, Sergio; Stringa, Pablo; Vallejo, Maria Teresa; Largo, Carlota; Encinas, Jose Luis; Garcia de Las Heras, Maria Soledad; Lopez-Santamaria, Manuel; Tovar, Juan Antonio

    2016-05-01

    Experimental small bowel transplantation (SBT) in rats has been proven to be a useful tool for the study of ischemia-reperfusion and immunological aspects related to solid organ transplantation. However, the model is not completely refined, specialized literature is scarce and complex technical details are typically omitted or confusing. Most studies related to acute rejection (AR) use the orthotopic standard, with small sample sizes due to its high mortality, whereas those studying chronic rejection (CR) use the heterotopic standard, which allows longer term survival but does not exactly reflect the human clinical scenario. Various animal strains have been used, and the type of rejection and the timing of its analysis differ among authors. The double purpose of this study was to develop an improved unusual AR model of SBT using the heterotopic technique, and to elaborate a guide useful to implement experimental models for studying AR. We analyzed the model's technical details and expected difficulties in overcoming the learning curve for such a complex microsurgical model, identifying the potential problem areas and providing a step-by-step protocol and reference guide for future surgeons interested in the topic. We also discuss the historic and more recent options in the literature. PMID:27102447

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

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

    2011-01-01

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

  1. Mycophenolate mofetil: safety and efficacy in the prophylaxis of acute kidney transplantation rejection

    Pranav Dalal

    2009-01-01

    Full Text Available Pranav Dalal1, Monica Grafals2, Darshika Chhabra2, Lorenzo Gallon21Department of Medicine, Mount Sinai Hospital, Chicago, USA; 2Northwestern University–Feinberg School of Medicine, Chicago, USAAbstract: Mycophenolate mofetil (MMF, a prodrug of mycophenolic acid (MPA, is an inhibitor of inosine monophosphate dehydrogenase (IMPDH. It preferentially inhibits denovo pathway of guanosine nucleotide synthesis in T and B-lymphocytes and prevents their proliferation, thereby suppresses both cell mediated and humoral immune responses. Clinical trials in kidney transplant recipients have shown the efficacy of MMF in reducing the incidence and severity of acute rejection episodes. It also improves long term graft function as well as graft and patient survival in kidney transplant recipients. MMF is useful as a component of toxicity sparing regimens to reduce or avoid exposure of steroids or calcineurin inhibitor (CNI. Enteric-coated mycophenolate sodium (EC-MPS can be used as an alternative immunosuppressive agent in kidney transplant recipients with efficacy and safety profile similar to MMF.Keywords: mycophenolate mofetil, kidney transplantation, acute rejection, toxicity sparing

  2. Activation of counter-regulatory mechanisms in a rat renal acute rejection model

    Salomon Daniel R

    2008-02-01

    Full Text Available Abstract Background Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.

  3. Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients

    Loftheim Håvard

    2012-08-01

    Full Text Available Abstract Background Acute rejection (AR episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Non-invasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population. Methods In this proof of principle study, serial urine samples in the early post transplant phase from 6 patients with biopsy verified acute rejections and 6 age-matched controls without clinical signs of rejection were analyzed by shotgun proteomics. Results Eleven proteins fulfilled predefined criteria for regulation in association with AR. They presented detectable regulation already several days before clinical suspicion of AR (increased plasma creatinine. The regulated proteins could be grouped by their biological function; proteins related to growth and proteins related to immune response. Growth-related proteins (IGFBP7, Vasorin, EGF and Galectin-3-binding protein were significantly up-regulated in association with AR (P = 0.03 while proteins related to immune response (MASP2, C3, CD59, Ceruloplasmin, PiGR and CD74 tended to be up-regulated ( P = 0.13. Conclusion The use of shotgun proteomics provides a robust and sensitive method for identification of potentially predictive urinary biomarkers of AR. Further validation of the current findings is needed to establish their potential clinical role with regards to clinical AR diagnosis. Trial registration ClinicalTrials.gov number NCT00139009

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

    Christensen, Hanne Krarup; Johannesen, Helle Hjorth; Christensen, Anders Fogh; Bendtzen, Klaus; Boysen, Gudrun Margrethe

    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...

  5. Belatacept for prevention of acute rejection in adult patients who have had a kidney transplant: an update

    Wojciechowski D; Vincenti F

    2012-01-01

    David Wojciechowski, Flavio VincentiKidney Transplant Service, University of California, San Francisco, CA, USAAbstract: In June 2011, the US Food and Drug Administration approved belatacept for the prophylaxis of organ rejection in adult kidney transplant recipients. This review discusses the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen. Belatacept is a selective costimulation blocker designed to provide effective immunosuppressio...

  6. The use of 111In-labelled lymphocyte imaging to evaluate graft rejection following cardiac transplantation in dogs

    Lymphocytes separated from venous blood from six dogs who had heterotopic cardiac transplants have been labeled using 111In-oxine. Labeled lymphocytes were reinjected into the dogs and imaging for the heart carried out over the successive 3 or 4 days. For comparison serial ECGs and punch biopsies of the heart was clearly visible in three of the six dogs, faintly visible in two and not seen in one. 630 μCi111In was used in the dog where no uptake was seen and subsequent studies showed this amount of the radiopharmaceutical was toxic to lymphocytes. In the remaining five dogs the mean ratio of uptake of 111In in donor to recipient heart was 14:1 (range 6.5:1-21:1). The lack of substantial uptake in the transplanted heart of two dogs is attributed to a delay in rejection relative to the time the labled lymphocytes were injected. The results suggest that 111In-labeled lymphocytes have potential as a noninvasive test for detecting rejection of cardiac transplants. (orig.)

  7. Acute antibody-mediated rejection after ABO-incompatible kidney transplantation treated successfully with antigen-specific immunoadsorption

    Just, Søren Andreas; Marcussen, Niels; Sprogøe, Ulrik; Koefoed-Nielsen, Pernille; Bistrup, Claus

    2010-01-01

    ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody-mediated reje...... that ABO-incompatible kidney transplantation complicated by acute antibody-mediated rejection, caused by ABO antibodies, may successfully be treated with this regime.......ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody......-mediated rejection (Banff grade II with IgG deposits) caused by ABO antibodies (anti-B). Anti-rejection treatment with anti-B-specific immunoadsorption, intravenous immunoglobulin and methylprednisolone efficiently cleared deposited IgG from the kidney allograft and re-established normal kidney function. We suggest...

  8. Acute antibody-mediated rejection after AB0-incomptible kidney transplantation treated successfully with antigen-specific immunoadsorption

    Just, Søren Andreas; Marcussen, Niels; Sprogøe, Ulrik; Kofoed-Nielsen, Pernille Bundgaard; Bistrup, Claus

    2009-01-01

    ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody-mediated reje...... that ABO-incompatible kidney transplantation complicated by acute antibody-mediated rejection, caused by ABO antibodies, may successfully be treated with this regime.......ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody......-mediated rejection (Banff grade II with IgG deposits) caused by ABO antibodies (anti-B). Anti-rejection treatment with anti-B-specific immunoadsorption, intravenous immunoglobulin and methylprednisolone efficiently cleared deposited IgG from the kidney allograft and re-established normal kidney function. We suggest...

  9. Clinical Implications and Risk Factors of Acute Pancreatitis after Cardiac Valve Surgery

    Chung, Joo Won; Ryu, Sung Ho; Jo, Jung Hyun; Park, Jeong Youp; Lee, Sak; Park, Seung Woo; Song, Si Young; Chung, Jae Bock

    2012-01-01

    Purpose Acute pancreatitis is one of the potentially lethal complications that occurs after cardiac surgery. We tried to identify risk factors for and the prognosis of acute pancreatitis after cardiac valve surgery with cardiopulmonary bypass. Materials and Methods We retrospectively analyzed a database of consecutive patients who underwent cardiac valve surgery with cardiopulmonary bypass between January 2005 and April 2010 at our institution. Patients were classified as having acute pancrea...

  10. Adiponectin Ameliorates Endotoxin-Induced Acute Cardiac Injury

    Yoshio Watanabe

    2014-01-01

    Full Text Available Background. Obesity is a risk factor for cardiovascular disease. Increasing evidence suggests that reduced levels of the adipocyte-derived plasma protein adiponectin are associated with an increased cardiovascular risk. Here, we examined the effects of adiponectin on lipopolysaccharide- (LPS- induced acute cardiac injury in vivo. Methods and Results. A single dose of LPS (10 mg/kg was intraperitoneally injected into wild-type (WT and adiponectin-knockout (APN-KO mice. Following LPS administration, APN-KO mice had exacerbation of left ventricular (LV systolic dysfunction compared with WT mice. Administration of LPS to WT and APN-KO mice led to an increased expression of inflammatory cytokines including TNF-α and IL-6 in the heart, but the magnitude of this induction was greater in APN-KO mice compared to WT mice. Systemic delivery of an adenoviral vector expressing adiponectin (Ad-APN improved LPS-induced LV dysfunction in APN-KO mice, and this effect was accompanied by the reduced expression of TNF-α and IL-6 in the heart. Administration of etanercept, a soluble TNF receptor abolished the reduced LV contractile function in response to LPS in APN-KO mice. Conclusion. These results suggest that adiponectin protects against LPS-induced acute cardiac injury by suppressing cardiac inflammatory responses, and could represent a potential therapeutic target in sepsis-associated myocardial dysfunction.

  11. Acute kidney injury in septua- and octogenarians after cardiac surgery

    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.

  12. 99mTc-tin colloid scintigraphy in the diagnosis of acute rejection. Reactions of renal transplants

    Quantitative measurements of 99mTc-tin colloid uptake in renal transplants permits differentiation of acute rejection from other causes of deteriorating renal function, such as acute tubular necrosis, cyclosporin A nephrotoxicity or chronic rejection. 144 99mTc-tin colloid scintigrams were performed on 71 renal transplants; the results were compared with clinical, biochemical and histological findings. Sensitivity of colloid scintigraphy is 97.4% and specificity is 80%. Compared with other isotope methods, this has the advantage that it does not depend on comparison with repeated examinations. (orig.)

  13. Efficacy of rabbit anti-thymocyte globulin for steroid-resistant acute rejection after liver transplantation.

    Lee, Jae Geun; Lee, Juhan; Lee, Jung Jun; Song, Seung Hwan; Ju, Man Ki; Choi, Gi Hong; Kim, Myoung Soo; Choi, Jin Sub; Kim, Soon Il; Joo, Dong Jin

    2016-06-01

    Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child-Turcotte-Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients' median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver transplant recipients

  14. Analysis of NAD(P)H fluorescence components in cardiac myocytes from human biopsies: a new tool to improve diagnostics of rejection of transplanted patients

    Cheng, Y.; Mateasik, A.; Poirier, N.; Miró, J.; Dahdah, N.; Chorvat, D., Jr.; Chorvatova, A.

    2009-02-01

    Tissue autofluorescence is one of the most versatile non-invasive tools for mapping the metabolic state in living tissues. Increasing interest in the imaging and diagnosis of living cells and tissues, based on their intrinsic fluorescence rather than fluorescence labeling, is closely connected to the latest developments in high-performance spectroscopic and microscopic techniques. We investigate metabolic state of cardiac cells isolated from one additional human biopsy from transplanted pediatric patients presenting either no rejection (R0) or mild rejection (R1). Two different approaches for isolation of human cardiac myocytes are also compared. Spectrally-resolved fluorescence lifetime detection of NAD(P)H fluorescence (excitation by pulsed 375 nm picosecond laser) is tested as a promising new tool for quantitative analysis of intrinsic cellular autofluorescence signals in living cardiomyocytes. This work opens new horizons in the evaluation of cardiac transplant rejection using latest fluorescence imaging approaches.

  15. Acute Rejection Associated with Donor-Specific Anti-MICA Antibody in a Highly Sensitized Pediatric Renal Transplant Recipient

    Narayan, Shoba; Tsai, Eileen W.; Zhang, Qiuheng; Wallace, William D.; Reed, Elaine F.; Ettenger, Robert B.

    2013-01-01

    Allograft rejection in HLA identical transplant recipients and in patients without detectable donor specific anti-HLA antibodies has lead to the identification of non-HLA antigens as targets of the alloimmune response. Major Histocompatibility Complex class I-related chain A (MICA) antigen has been recognized as an important non-HLA target in renal transplantation. Recent studies have shown that anti-MICA antibodies are associated with acute renal allograft rejection and failure. Current cross match procedures using donor lymphocytes fail to detect MICA antibodies. Transplant candidates are not routinely tested for pre-sensitization to MICA antigens nor are transplant donors typed for MICA alleles. Optimal classification and treatment of acute rejection associated with MICA antibody remains unknown. In this case report, we are the first to describe the clinical course and treatment of donor specific MICA antibody associated with both Banff type II A acute cellular rejection (ACR) and antibody mediated rejection (AMR) in a highly sensitized pediatric renal re-transplant recipient. This case also emphasizes the importance of pre-transplant screening for donor specific MICA antibody especially in highly sensitized renal transplant patients.. PMID:21199204

  16. Functional changes of dendritic cells derived from allogeneic partial liver graft undergoing acute rejection in rats

    Ming-Qing Xu; Zhen-Xiang Yao

    2003-01-01

    4 days after transplantation (P<0.001) was observed.CONCLUSION: DCs derived from allogeneic partial liver graftundergoing acute rejection display features of mature DC.

  17. Derivation and Validation of a Cytokine-Based Assay to Screen for Acute Rejection in Renal Transplant Recipients

    De Serres, Sacha A.; Mfarrej, Bechara G.; Grafals, Monica; Riella, Leonardo V.; Magee, Ciara N.; Yeung, Melissa Y.; Dyer, Christine; Ahmad, Usaila; Chandraker, Anil

    2012-01-01

    Summary Background and objectives Acute rejection remains a problem in renal transplantation. This study sought to determine the utility of a noninvasive cytokine assay in screening of acute rejection. Design, setting, participants, & measurements In this observational cross-sectional study, 64 patients from two centers were recruited upon admission for allograft biopsy to investigate acute graft dysfunction. Blood was collected before biopsy and assayed for a panel of 21 cytokines secreted by PBMCs. Patients were classified as acute rejectors or nonrejectors according to a classification rule derived from an initial set of 32 patients (training cohort) and subsequently validated in the remaining patients (validation cohort). Results Although six cytokines (IL-1β, IL-6, TNF-α, IL-4, GM-CSF, and monocyte chemoattractant protein-1) distinguished acute rejectors in the training cohort, logistic regression modeling identified a single cytokine, IL-6, as the best predictor. In the validation cohort, IL-6 was consistently the most accurate cytokine (area under the receiver-operating characteristic curve, 0.85; P=0.006), whereas the application of a prespecified cutoff level, as determined from the training cohort, resulted in a sensitivity and specificity of 92% and 63%, respectively. Secondary analyses revealed a strong association between IL-6 levels and acute rejection after multivariate adjustment for clinical characteristics (P<0.001). Conclusions In this pilot study, the measurement of a single cytokine can exclude acute rejection with a sensitivity of 92% in renal transplant recipients presenting with acute graft dysfunction. Prospective studies are needed to determine the utility of this simple assay, particularly for low-risk or remote patients. PMID:22498498

  18. Case of Acute Graft Failure during Suspected Humoral Rejection with Preserved Ejection Fraction, but Severely Reduced Longitudinal Deformation Detected by 2D-Speckle Tracking

    Clemmensen, Tor Skibsted; Eiskjær, Hans; Kofoed-Nielsen, Pernille B;

    2014-01-01

    remained unchanged, indicating need of more reliable noninvasive methods for graft function surveillance. Global longitudinal strain relates to clinical heart failure, filling pressure, and cardiac index during suspected humoral rejection and microvascular dysfunction in this HTX patient. We suggest...

  19. Temporal profile of calcineurin phosphatase activity during acute allograft rejection in the heterotopic rat heart transplantation model

    Karamperis, N; Koefoed-Nielsen, P B; Marcussen, N;

    2008-01-01

    it can be utilized as a pharmacodynamic marker to identify and monitor the rejection process. METHODS: The heterotopic cervical rat heart transplantation model was used (dark Agouti to Lewis). We performed 25 control isogeneic and 46 allogeneic transplantations. Rats were sacrificed at various...... as a pharmacodynamic biomarker of acute allograft rejection in the heterotopic rat heart transplantation model. Further research is required in order to reveal the precise role of CaN during acute allograft rejection....... postoperative time points. CaN activity was measured in isolated peripheral blood and spleen mononuclear cells and in graft heart homogenates. CaN activity was measured as the release of radiolabeled phosphate from a previously phosphorylated 19 amino acid peptide. RESULTS: We have shown that CaN's activity...

  20. Elevated mRNA levels of CTLA-4, FoxP3, and granzyme B in BAL, but not in blood, during acute rejection of lung allografts

    Madsen, Caroline B; Nørgaard, Astrid; Iversen, Martin;

    2010-01-01

    Regulatory T cells (Tregs) have been related to acute rejection as have the cytotoxic T cells, their immunological counterpart. High expression of cytotoxic markers has been related to acute rejection incidents following both kidney and intestine transplantation, while the correlation between FoxP3...

  1. Lack of association of recipient MCP-1 gene promoter polymorphism with acute graft rejection after orthotopic liver transplantation.

    Franco-López, E; González-Escribano, M F; Aguilera, I; Pascasio, J M; Pareja, F; Bernardos, A; Núñez-Roldán, A

    2005-04-01

    Acute graft rejection after orthotopic liver transplantation (OLT) is associated with leukocyte infiltration of the graft. Monocyte chemoattractant protein-1 (MCP-1) is a beta-chemokine involved in the attraction and accumulation of mononuclear granulocytes toward sites of inflammation. A biallelic polymorphism (G/A) at position -2518 of the MCP-1 gene has been described. Cells obtained from individuals with the GG or AG genotypes have been found to produce more MCP-1 than those obtained from individuals with the AA genotype. The goal of this study was to assess the possible association between this polymorphism and susceptibility to acute graft rejection after OLT. One hundred fifty Caucasian liver transplant recipients from the South of Spain underwent genotyping using a polymerase chain reaction (PCR) amplification followed by restriction fragment length polymorphism (RFLP). No significant differences were observed when patients with versus without acute rejection episodes were compared for the distribution of -2518 MCP-1 genotypes. The present study supports the lack of involvement of polymorphism at position -2518 (A/G) of the MCP-1 gene on the susceptibility to acute allograft rejection among OLT recipients. PMID:15866653

  2. Serial changes in longitudinal graft function and implications of acute cellular graft rejections during the first year after heart transplantation

    Clemmensen, Tor Skibsted; Løgstrup, Brian Bridal; Eiskjær, Hans;

    2015-01-01

    AIMS: The aim of this prospective study was to use left ventricular global longitudinal strain (LV-GLS) as a non-invasive tool for the monitoring of graft function in relation to acute cellular rejection (ACR) during the first year after heart transplantation (HTX). METHODS AND RESULTS: The study...

  3. Performance of polymerase chain reaction techniques detecting perforin in the diagnosis of acute renal rejection: a meta-analysis.

    Yushu Shang

    Full Text Available BACKGROUND: Studies in the past have shown that perforin expression is up-regulated during acute renal rejection, which provided hopes for a non-invasive and reliable diagnostic method to identify acute rejection. However, a systematic assessment of the value of perforin as a diagnostic marker of acute renal rejection has not been performed. We conducted this meta-analysis to document the diagnostic performance of perforin mRNA detection and to identify potential variables that may affect the performance. METHODOLOGY/PRINCIPAL FINDINGS: Relevant materials that reported the diagnostic performance of perforin mRNA detection in acute renal rejection patients were extracted from electronic databases. After careful evaluation of the studies included in this analysis, the numbers of true positive, true negative, false positive and false negative cases of acute renal rejection identified by perforin mRNA detection were gathered from each data set. The publication year, sample origin, mRNA quantification method and housekeeping gene were also extracted as potential confounding variables. Fourteen studies with a total of 501 renal transplant subjects were included in this meta-analysis. The overall performance of perforin mRNA detection was: pooled sensitivity, 0.83 (95% confidence interval: 0.78 to 0.88; pooled specificity, 0.86 (95% confidence interval: 0.82 to 0.90; diagnostic odds ratio, 28.79 (95% confidence interval: 16.26 to 50.97; and area under the summary receiver operating characteristic curves value, 0.9107±0.0174. The univariate analysis of potential variables showed some changes in the diagnostic performance, but none of the differences reached statistical significance. CONCLUSIONS/SIGNIFICANCE: Despite inter-study variability, the test performance of perforin mRNA detected by polymerase chain reaction was consistent under circumstances of methodological changes and demonstrated both sensitivity and specificity in detecting acute renal

  4. Belatacept for prevention of acute rejection in adult patients who have had a kidney transplant: an update

    Wojciechowski, David; Vincenti, Flavio

    2012-01-01

    In June 2011, the US Food and Drug Administration approved belatacept for the prophylaxis of organ rejection in adult kidney transplant recipients. This review discusses the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen. Belatacept is a selective costimulation blocker designed to provide effective immunosuppression while avoiding the toxicities associated with calcineurin inhibitors. Phase III trial data have demonstrated that belatacept is noninferior to cyclosporine in 1-year patient and allograft survival. Three-year data demonstrate an ongoing improvement in mean measured glomerular filtration rate in belatacept-treated versus cyclosporine-treated patients. However, the rate of acute rejection was higher in belatacept-treated patients compared with cyclosporine. Specifically, there was a higher incidence of Banff type II rejections in patients treated with belatacept. Despite the higher Banff grade, rejections on belatacept were not associated with other factors associated with poor outcomes, such as the development of donor-specific antibodies or reduced estimated glomerular filtration rate. One safety issue that must be considered when using belatacept is the potential for increased risk of post-transplant lymphoproliferative disease. There were more cases of post-transplant lymphoproliferative disease in belatacept-treated patients, especially in recipients seronegative for Epstein–Barr virus or patients treated with lymphocyte-depleting agents. Therefore, belatacept can be recommended for use in Epstein–Barr virus antibody-positive recipients. PMID:23152668

  5. Gastroesophageal Reflux Disease Is Associated With an Increased Rate of Acute Rejection in Lung Transplant Allografts

    Shah, N.S.; Force, S.D.; Mitchell, P.O.; Lin, E.; Lawrence, E.C.; Easley, K.; Qian, J.; Ramirez, A.; Neujahr, D.C.; Gal, A.; Leeper, K.; Pelaez, A.

    2012-01-01

    Purpose Gastric fundoplication (GF) for gastroesophageal reflux disease (GERD) may protect against the progression of chronic rejection in lung transplant (LT) recipients. However, the association of GERD with acute rejection episodes (ARE) is uncertain. This study sought to identify if ARE were linked to GERD in LT patients. Methods This single-center retrospective observational study, of patients transplanted from January 1, 2000, to January 31, 2009, correlated results of pH probe testing for GERD with ARE (≥International Society for Heart and Lung Transplantation A1 or B1). We compared the rates of ARE among patients with GERD (DeMeester Score > 14.7) versus without GERD as number of ARE per 1,000 patient-days after LT. Patients undergoing GF prior to LT were excluded. Results The analysis included 60 LT subjects and 9,249 patient-days: 33 with GERD versus 27 without GERD. We observed 51 ARE among 60 LT recipients. The rate of ARE was highest among patients with GERD: 8.49 versus 2.58, an incidence density ratio (IDR) of 3.29 (P = .00016). Upon multivariate negative binomial regression modeling, only GERD was associated with ARE (IDR 2.15; P = .009). Furthermore, GERD was associated with multiple ARE (36.4% vs 0%; P < .0001) and earlier onset compared with patients without GERD: ARE proportion at 2 months was 0.55 versus 0.26 P = .004). Conclusion In LT recipients, GERD was associated with a higher rate, multiple events, and earlier onset of ARE. The efficacy of GF to reduce ARE among patients with GERD needs further evaluation. PMID:20832573

  6. Electrocardiographic findings and cardiac manifestations in acute aluminum phosphide poisoning.

    Soltaninejad, Kambiz; Beyranvand, Mohammad-Reza; Momenzadeh, Seyed-Akbar; Shadnia, Shahin

    2012-07-01

    Aluminium phosphide (AlP) poisoning has a high mortality due to cardiovascular involvement. In this study, we evaluated the frequency of cardiac manifestations and electrocardiographic (ECG) findings in 20 patients with acute AlP poisoning, who were admitted to the intensive care unit (ICU) in Tehran, Iran, over a period of 6 months (between October 2008 and April 2009). The sex, age, cause and manner of ingestion, number of ingested AlP tablets, cardiac and ECG manifestations, creatine phosphokinase (CPK), CPK-myocardial band (CPK-mb) and troponin-T (TnT) were extracted from the patients' files. All data were analysed with Statistical Package for the Social Sciences (SPSS) software. The majority (60%) of patients were male. The mean age was 27 ± 8.7 years. The mortality rate was 40%. In all of the patients, the cause of poisoning was intentional suicide and ingestion was the route of exposure. The mean number of ingested AlP tablets per patient was 2.2 ± 1.1. The average time interval between admission and cardiovascular manifestations or ECG findings was 168.8 ± 116.2 min. The range of systolic (SBP) and diastolic blood pressure was 60-130 mmHg and 40-70 mmHg, respectively. Dysrhythmia was observed in nine (45%) cases. Elevation of the ST segment was seen in nine cases (45%). Seven patients (35%) had prolonged QTc intervals. Bundle branch block (BBB) was observed in four (20%) patients. In nine (45%) patients, the serum cardiac TnT qualitative assay was positive. There were no significant differences between normal and abnormal ECG groups according to sex, age, number and manner of ingested AlP tablets and SBP. There was a significant correlation between cardiac manifestations and ECG findings and TnT-positive results with mortality in acute AlP poisoning. PMID:22687771

  7. Belatacept for prevention of acute rejection in adult patients who have had a kidney transplant: an update

    Wojciechowski D

    2012-11-01

    Full Text Available David Wojciechowski, Flavio VincentiKidney Transplant Service, University of California, San Francisco, CA, USAAbstract: In June 2011, the US Food and Drug Administration approved belatacept for the prophylaxis of organ rejection in adult kidney transplant recipients. This review discusses the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen. Belatacept is a selective costimulation blocker designed to provide effective immunosuppression while avoiding the toxicities associated with calcineurin inhibitors. Phase III trial data have demonstrated that belatacept is noninferior to cyclosporine in 1-year patient and allograft survival. Three-year data demonstrate an ongoing improvement in mean measured glomerular filtration rate in belatacept-treated versus cyclosporine-treated patients. However, the rate of acute rejection was higher in belatacept-treated patients compared with cyclosporine. Specifically, there was a higher incidence of Banff type II rejections in patients treated with belatacept. Despite the higher Banff grade, rejections on belatacept were not associated with other factors associated with poor outcomes, such as the development of donor-specific antibodies or reduced estimated glomerular filtration rate. One safety issue that must be considered when using belatacept is the potential for increased risk of post-transplant lymphoproliferative disease. There were more cases of post-transplant lymphoproliferative disease in belatacept-treated patients, especially in recipients seronegative for Epstein–Barr virus or patients treated with lymphocyte-depleting agents. Therefore, belatacept can be recommended for use in Epstein–Barr virus antibody-positive recipients.Keywords: belatacept, kidney transplant, acute rejection

  8. Human herpesvirus-6 and cytomegalovirus DNA in liver donor biopsies and their correlation with HLA matches and acute cellular rejection

    Ana Carolina Guardia

    2014-04-01

    Full Text Available Herpesvirus reactivation is common after liver transplantation. OBJECTIVE: Analyze the presence of cytomegalovirus (HCMV and human herpesvirus-6 (HHV-6 DNA in liver donor biopsies, seeking to better understand issues involving human donor leukocyte antigens (HLA-A, B and DR, as well as correlations with acute cellular rejection. METHODS: Fifty-nine liver transplantation patients were investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies, using the Nested-PCR technique. The clinical donor information and HLA matches were obtained from the São Paulo State Transplant System. The recipients' records regarding acute cellular rejection were studied. RESULTS: Seven (11.8% biopsies were positive for HCMV DNA and 29 (49% were positive for HHV-6 DNA. In 14 donors with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for significant association (p=0.09, 22 recipients developed acute cellular rejection and 9/22 were positive for HLA-DR 15 (p=0.03; χ 2=4.51, which was statistically significant in univariate analysis and showed a tendency after multivariate analysis (p=0.08. CONCLUSION: HHV-6 DNA was prevalent in liver donors studied as well as HLA-DR 15. These findings suggest that patients with HLA-DR 15 in liver donor biopsies develop more rejection after liver transplantation.

  9. Changes in dendritic cells and dendritic cell subpopulations in peripheral blood of recipients during acute rejection after kidney transplantation

    Ma Linlin; Liu Yong; Wu Junjie; Xu Xiuhong; Liu Fen; Feng Lang; Xie Zelin

    2014-01-01

    Background Advances in transplantation immunology show that the balance between dendritic cells (DCs) and their subsets can maintain stable immune status in the induction of tolerance after transplantation.The aim of this study was to investigate if DCs and DC subpopulations in recipient peripheral blood are effective diagnostic indicators of acute rejection following kidney transplantation.Methods Immunofluorescent flow cytometry was used to classify white blood cells (WBCs),the levels of mononuclear cells and DCs (including the dominant subpopulations,plasmacytoid DC (pDC) and myeloid DC (mDC)) in peripheral blood at 0,1,7,and 28 days and 1 year after kidney transplantation in 33 patients.In addition,the blood levels of interleukin-10 (IL-10) and IL-12 were monitored before and after surgery.Fifteen healthy volunteers served as normal controls.Patients were undertaking hemodialysis owing to uremia before surgery.Results The total number of DCs,pDC,and mDC in peripheral blood and the pDC/mDC ratio were significantly lower in patients than controls (P <0.05).Peripheral DCs suddenly decreased at the end of day 1,then gradually increased through day 28 but remained below normal levels.After 1 year,levels were higher than before surgery but lower than normal.The mDC levels were higher in patients with acute rejection before and 1 day after surgery (P <0.005).There was no significant difference in IL-10 and IL-12 levels between patients with and without acute rejection.Conclusion The changes in DCs and DC subpopulations during the acute rejection period may serve as effective markers and referral indices for monitoring the immune state,and predicting rejection and reasonably adjusting immunosuppressants.

  10. Does the circadian pattern for acute cardiac events presentation vary with fasting?

    Suwaidi Al; Bener A; Gehani A; Behair S; Mohanadi D; Salam A; Binali HA

    2006-01-01

    Background: Over one billion Muslims fast worldwide during the month of Ramadan. The impact of fasting on circadian presentation with acute cardiac events is unknown. Aim: To determine if fasting has any effect on the circadian presentation of acute cardiac events. Setting and Design: A prospective study in a general hospital. Materials and Methods: Patients with acute coronary events were divided into two groups based on the history of fasting. Information about age, gender, cardiova...

  11. The involvement of donor specific CTL in cardiac transplant rejection: relevance of avidity

    N.E.M. van Emmerik (Nancy)

    1998-01-01

    textabstractWhen a micro-organism penetrates the body, defensive mechanisms of the non-specific innate immune system come into play, such as soluble chemical factors (bactericidal lysozyme, acute phase proteins, interferons), extracellular killing (NK cells, eosinophils), and phagocytosis (macrophag

  12. Recipient Cytotoxic T Lymphocyte Antigen 4 +49 Single-Nucleotide Polymorphism Is Not Associated with Acute Rejection after Liver Transplantation in Chinese Population

    Zhijun Jiang, Ying Chen, Xiaonin Feng, Haiyang Xie, Lin Zhou, Shusen Zheng

    2013-01-01

    Full Text Available Objective: Single-nucleotide polymorphisms (SNPs in Cytotoxic T lymphocyte antigen 4 (CTLA-4 gene have been detected and proved to associate with the incidence of rejection after transplantation. However, previous studies gained inconsistent results about the association between CTLA-4 +49 single-nucleotide polymorphism and susceptibility of allograft rejection. Therefore we sought to clarify whether CTLA-4 +49 SNP influences the incidence of acute rejection after liver transplantation in Chinese population. Methods: Genomic DNA from 335 liver transplant recipients was genotyped for CTLA-4 +49 SNP by DNA sequencing. Acute rejection was confirmed by pathologic evidences. The association between CTLA-4 +49 SNP and incidence of acute rejection was then analyzed by dominant, recessive, codominant and overdominant models. Results: The incidence of acute rejection within the first 3 months was 11.9%. In acute rejectors, the frequency was 45% for G/G, 10% for A/A and 45% for A/G respectively, compared with 47.5% for G/G, 10.8% for A/A and 41.7% for A/G in non-acute rejectors. And no significant difference of allele distribution between these 2 groups was detected. Conclusions: This study suggests that CTLA-4 +49 SNP is not associated with acute rejection after liver transplantation in Chinese population.

  13. Cortex perfusion index: a sensitive detector of acute rejection crisis in transplanted kidneys

    Damage to the renal cortical microcirculation, an early event in the course of acute rejection crisis (ARC), usually precedes measurable functional derangements in the transplanted kidney. Direct assessment of cortical blood flow by radionuclide renography may provide a sensitive and reliable index to the diagnosis of ARC, with particular regard to the differential diagnosis of ARC and ATN. Computer generated time-activity curves of global, cortical, and medullary renal blood flow were analyzed in 67 instances (35 patients) of renal allograft dysfunction and correlated with needle biopsy of these kidneys. No increase in cortex perfusion index (CPI), i.e., decrease in cortical perfusion, was found when the patients were suffering from ureteral obstruction or drug and viral nephropathy (mean perfusion index (PI) increase (8%). In contrast, a marked increase in CPI of 193% was noted in ARC. Global and medullary PI increased only 116%. As a result, global and medullary PI were capable of diagnosing ARC in only 73% and 55% of the cases, respectively, whereby cortex PI correctly diagnosed ARC in 94% of the cases. Selective analysis of cortical perfusion may thus enhance the accuracy of [99mTc]DTPA scans (radionuclide renograph) for the early detection of ARC and in differentiating ARC from nonimmunological causes of kidney allograft dysfunction

  14. Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

    Nassim Kamar; Laurence Lavayssière; Fabrice Muscari; Janick Selves; Céline Guilbeau-Frugier; Isabelle Cardeau; Laure Esposito; Olivier Cointault; Marie Béatrice Nogier; Jean Marie Peron; Philippe Otal; Marylise Fort; Lionel Rostaing

    2009-01-01

    Acute humoral rejection (AHR) is uncommon after ABOcompatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab.Liver enzymes returned to within normal range 18 dafter diagnosis. Liver biopsies, at 3 and 9 mo post-transplant,showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

  15. Expression of VE-Cadherin in Peritubular Endothelial Cells during Acute Rejection after Human Renal Transplantation

    Brigitte McGregor

    2007-07-01

    Full Text Available Genes involved in acute rejection (AR after organ transplantation remain to be further elucidated. In a previous work we have demonstrated the under-expression of VE-Cadherin by endothelial cells (EC in AR following murine and human heart transplantation. Serial sections from 15 human kidney Banff-graded transplant biopsies were examined for the presence of VE-Cadherin and CD34 staining by immunohistochemistry (no AR (n=5, AR grade IA (n=5, or AR grade IIA (n=5. Quantification of peritubular EC staining were evaluated and results were expressed by the percentage of stained cells per surface analysed. There was no difference in CD34 staining between the 3 groups. VE-Cadherin expression was significantly reduced in AR Grade IIA when compared to no AR (P=.01 and to AR grade IA (P=.02. This study demonstrates a reduced VE-Cadherin expression by EC in AR after renal transplantation. The down-regulation of VE-Cadherin may strongly participate in human AR.

  16. Is biliary bile acid a good predictor for acute cellular rejection in living donor liver transplantation?

    Mohammed Saied Hedaya; Walid M. El Moghazy; YamamotoYasutomo; Tomioka Kiyoshi; Toshimi Kaido; Hiroto Egawa; Shinji Uemoto; Yasutsugu Takada

    2009-01-01

    BACKGROUND: In liver transplantation, acute cellular rejection (ACR) is still a major complication that can lead to mortality. Bile secretion has been considered as a marker of early graft function. METHODS: The study included 41 adults who received living donor liver transplantation (LDLT) at Kyoto University Hospital between April 2007 and February 2008. The patients were stratified according to the presence or absence of ACR. Bile samples were collected from donors once and from recipients every other day for the first 2 weeks after transplantation. Total bile acid (BA) and taurine-conjugated bile acid (TCBA) in bile were measured by magnetic resonance spectroscopy. The recipient/donor (R/D) BA ratio and R/D TCBA ratio were calculated. RESULTS: The ACR group (n=12) showed a greater decrease in BA post-transplantation than the non-ACR group, but this difference was not statistically significant. On both day 7 and day 9 post-transplantation the R/D TCBA was significantly different between the two groups (P=0.038 on day 7 and P=0.036 on day 9). The R/D TCBA ratio ≥0.5 on days 7 and 9, and ≥0.38 on day 11 post-transplantation were associated with better ACR-free survival. CONCLUSION: The recipient/donor TCBA ratio can be a predictor for ACR after LDLT as early as post-transplantation day 7.

  17. The involvement of donor specific CTL in cardiac transplant rejection: relevance of avidity

    Emmerik, Nancy

    1998-01-01

    textabstractWhen a micro-organism penetrates the body, defensive mechanisms of the non-specific innate immune system come into play, such as soluble chemical factors (bactericidal lysozyme, acute phase proteins, interferons), extracellular killing (NK cells, eosinophils), and phagocytosis (macrophages, polymorphonuclear neutrophils). This innate immune system is supported by the specific acquired immune system which comprises of B- and Tlymphocytes. These lymphocytes are educated to distingui...

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

    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.

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

    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)

  20. T cell immunohistochemistry refines lung transplant acute rejection diagnosis and grading

    Cheng, Lin; Guo, Haizhou; Qiao, Xinwei; Liu, Quan; Nie, Jun; Li, Jinsong; Wang, JianJun; Jiang, Ke

    2013-01-01

    Objective Lung transplant volume has been increasing. However, inaccurate and uncertain diagnosis for lung transplant rejection hurdles long-term outcome due to, in part, interobserver variability in rejection grading. Therefore, a more reliable method to facilitate diagnosing and grading rejection is warranted. Method Rat lung grafts were harvested on day 3, 7, 14 and 28 post transplant for histological and immunohistochemical assessment. No immunosuppressive treatment was administered. We e...

  1. Methylprednisolone-hemisuccinate and its metabolites in serum, urine and bile from two patients with acute graft rejection.

    Lawson, G. J.; Chakraborty, J; Tredger, J M; Baylis, E M

    1995-01-01

    Methylprednisolone-hemisuccinate (MPHS), methylprednisolone (MP), 20-alpha-hydroxy- (20 alpha HMP) and 20-beta-hydroxymethyl-prednisolone (20 beta HMP) concentrations were measured in serum, urine and bile from two liver transplant recipients who had received 1 g MPHS by a 1 h intravenous infusion for treatment of an acute rejection episode. These patients excreted similar total amounts of the dose in urine as patients with rheumatoid arthritis (historical controls) who had normal liver funct...

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

    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)

  3. Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review

    Toma Mustafa

    2009-03-01

    Full Text Available Abstract Background Screening for organ rejection is a critical component of care for patients who have undergone heart transplantation. Endomyocardial biopsy is the gold standard screening tool, but non-invasive alternatives are needed. Cardiovascular magnetic resonance (CMR is well suited to provide an alternative to biopsy because of its ability to quantify ventricular function, morphology, and characterize myocardial tissue. CMR is not widely used to screen for heart transplant rejection, despite many trials supporting its use for this indication. This review summarizes the different CMR sequences that can detect heart transplant rejection as well as the strengths and weaknesses of their application. Results T2 quantification by spin echo techniques has been criticized for poor reproducibility, but multiple studies show its utility in screening for rejection. Human and animal data estimate that T2 quantification can diagnose rejection with sensitivities and specificities near 90%. There is also a suggestion that T2 quantification can predict rejection episodes in patients with normal endomyocardial biopsies. T1 quantification has also shown association with biopsy proven rejection in a small number of trials. T1 weighted gadolinium early enhancement appeared promising in animal data, but has had conflicting results in human trials. Late gadolinium enhancement in the diagnosis of rejection has not been evaluated. CMR derived measures of ventricular morphology and systolic function have insufficient sensitivity to diagnose mild to moderate rejection. CMR derived diastolic function can demonstrate abnormalities in allografts compared to native human hearts, but its ability to diagnose rejection has not yet been tested. There is promising animal data on the ability of iron oxide contrast agents to illustrate the changes in vascular permeability and macrophage accumulation seen in rejection. Despite good safety data, these contrast agents have

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

    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 with...

  5. Ventricular function during the acute rejection of heterotopic transplanted heart: Gated blood pool studies

    Twenty patients who had undergone a heterotopic heart transplant were studied prospectively to determine the relationship between rejection and ventricular dysfunction assessed from gated blood pool studies. A fully automated method for detecting ventricular edges was implemented; its success rate for the grafted left and right ventricles was 94% and 77%, respectively. The parameters, peak ejection and filling rates, were calculated pixel per pixel using a two-harmonic Fourier algorithm and then averaged over the ventricular region of interest. Peak filling and ejection rates were closely related with the severity of the rejection, while the left ventricular ejection fraction was not. Peak filling rates of both ventricles were the indices closely related to the presence of moderate rejection. Despite the low number of patients, these data suggested that gated blood pool derived indices of ventricular function are associated with ventricular dysfunction resulting from myocarditis rejection. Radionuclide ventriculography provides parametric data which are accurate and reliable for the diagnosis of rejection. (orig.)

  6. Existence of circulating anti-endothelial cell antibodies after heart transplantation is associated with post-transplant acute allograft rejection.

    Lehle, Karla; Kroher, Johannes; Kolat, Philipp; von Süßkind-Schwendi, Marietta; Schmid, Christof; Haneya, Assad; Rupprecht, Leopold; Hirt, Stephan

    2016-05-01

    Anti-endothelial cell antibodies (AECA) may be involved in the development of heart allograft rejection. Its detection might be a cheap and noninvasive method to identify high-risk patients. An indirect immunofluorescence method on human umbilical vein endothelial cells was used to investigate the presence of AECAs in 260 pre- and post-transplant serum samples sequentially collected from 34 patients within the first year after heart transplantation (HTX). The presence of AECAs before (23.5 %) and early after HTX (14.7 %) was associated with a significantly increased risk of early acute rejection (75 and 60 %, respectively) compared to 33 % in AECA-negative patients (p = 0.049). Moreover, rejections from AECA-positive patients were more severe (p = 0.057) with a significantly increased incidence of multiple (p = 0.025). The mean number of the sum of rejection episodes was significantly higher in AECA-positive patients (p ≤ 0.05). Patients free of AECAs mainly received mycophenolate mofetil as primary immunosuppression (p = 0.067). Nevertheless, the presence of AECAs did not affect long-term outcome and mortality of HTX patients. Despite a low number of patient samples, the detection of AECAs before and early after HTX could be used as a biomarker for an increased risk of early acute rejection in high-risk patients. This easy method might be a valuable tool to support screening procedures to improve individualized immunosuppressive therapy. PMID:25820657

  7. Increased Numbers of Circulating CD8 Effector Memory T Cells before Transplantation Enhance the Risk of Acute Rejection in Lung Transplant Recipients

    San Segundo, David; Ballesteros, María Ángeles; Naranjo, Sara; Zurbano, Felipe; Miñambres, Eduardo; López-Hoyos, Marcos

    2013-01-01

    The effector and regulatory T cell subpopulations involved in the development of acute rejection episodes in lung transplantation remain to be elucidated. Twenty-seven lung transplant candidates were prospectively monitored before transplantation and within the first year post-transplantation. Regulatory, Th17, memory and naïve T cells were measured in peripheral blood of lung transplant recipients by flow cytometry. No association of acute rejection with number of peripheral regulatory T cells and Th17 cells was found. However, effector memory subsets in acute rejection patients were increased during the first two months post-transplant. Interestingly, patients waiting for lung transplant with levels of CD8+ effector memory T cells over 185 cells/mm3 had a significant increased risk of rejection [OR: 5.62 (95% CI: 1.08-29.37), p=0.04]. In multivariate analysis adjusted for age and gender the odds ratio for rejection was: OR: 5.89 (95% CI: 1.08-32.24), p=0.04. These data suggest a correlation between acute rejection and effector memory T cells in lung transplant recipients. The measurement of peripheral blood CD8+ effector memory T cells prior to lung transplant may define patients at high risk of acute lung rejection. PMID:24236187

  8. INHALATION OF OZONE AND DIESEL EXHAUST PARTICLES (DEP) INDUCES ACUTE AND REVERSIBLE CARDIAC GENE EXPRESSION CHANGES

    We have recently shown that episodic but not acute exposure to ozone or DEP induces vascular effects that are associated with the loss of cardiac mitochondrial phospholipid fatty acids (DEP 2.0 mg/m3 > ozone, 0.4 ppm). In this study we determined ozone and DEP-induced cardiac gen...

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

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

    2015-01-01

    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 comple

  10. MOEMS-based cardiac enzymes detector for acute myocardial infarction

    Amritsar, Jeetender; Stiharu, Ion G.; Packirisamy, Muthukumaran; Balagopal, Ganesharam; Li, Xing

    2004-10-01

    Biomedical applications of MOEMS are limited only by the mankind imagination. Precision measurements on minute amounts of biological material could be performed by optical means with a remarkable accuracy. Although available in medical laboratories for general purposes, such analyzers are making their way directly to the users in the form of dedicated equipment. Such an example is a test kit to detect the existence of cardiac enzymes in the blood stream. Apart from the direct users, the medical personnel will make use of such tools given the practicality of the kit. In a large proportion of patients admitted to the hospital suspected of Acute Myocardial Infarction (AMI), the symptoms and electrocardiographic changes are inconclusive. This necessitates the use of biochemical markers of myocardial damage for correct exclusion or conformation of AMI. In this study the concept of MOEMS is applied for the detection of enzyme reaction, in which glass spectrums are scanned optically when enzyme molecules adsorb on their surface. This paper presents the optical behavior of glass spectrums under Horseradish Peroxide (HRP) enzyme reaction. The reported experimental results provide valuable information that will be useful in the development of biosensors for enzymatic detection. This paper also reports the dynamic behavior of different glass spectrums.

  11. Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery

    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.

  12. Assessment of different biomarkers provides valuable diagnostic standards in the evaluation of the risk of acute rejection

    Jin Zheng; Li Ren; Puxun Tian; Wujun Xue; Xiaoming Ding; Xiaohui Tian; Zhankui Jin; Xiaoming Pan; Hang Yan; Xinshun Feng; Jun Hou; Heli Xiang

    2012-01-01

    Acute rejection (AR) is a strong risk factor for chronic rejection in renal transplant recipients.Accurate and timely diagnosis of AR episodes is very important for disease control and prognosis.Therefore,objectively evaluated the immune status of patients is essential in the field of posttransplantation treatment.This longitudinal study investigated the usefulness of five biomarkers,human leukocyte antigen (HLA)-G5 and sCD30 level in sera,intracellular adenosine triphosphate (iATP) release level of CD4+ T cells,and granzyme B/perforin expression in peripheral blood mononuclear cells (PBMCs) and biopsies,to detect AR and the resolution of biomarkers in a total of 84 cases of renal transplantation.The data demonstrated that recipients with clinical or biopsy proven rejection significantly increased iATP release level of CD4+ T cells,and elevated sCD30 but lowered HLA-G5 level in sera compared with individuals with stable graft function.Expression levels of granzyme B and perforin were also elevated in PBMCs and graft biopsies of AR patients.Taken together,we identified that upregulation of sCD30,iATP,granzyme B,perforin,and downregulation of HLA-G5 could provide valuable diagnostic standards to identify those recipients in the risk of AR.And iATP may be a better biomarker than others for predicting the graft rejection episode.

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

    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.

  14. Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review

    Toma Mustafa; Haykowsky Mark; Thompson Richard; Butler Craig R; Paterson Ian

    2009-01-01

    Abstract Background Screening for organ rejection is a critical component of care for patients who have undergone heart transplantation. Endomyocardial biopsy is the gold standard screening tool, but non-invasive alternatives are needed. Cardiovascular magnetic resonance (CMR) is well suited to provide an alternative to biopsy because of its ability to quantify ventricular function, morphology, and characterize myocardial tissue. CMR is not widely used to screen for heart transplant rejection...

  15. 19F MRI Detection of Acute Allograft Rejection with In Vivo Perfluorocarbon Labeling of Immune Cells

    Hitchens, T. Kevin; Ye, Qing; Eytan, Danielle F.; Janjic, Jelena M.; Ahrens, Eric T.; Ho, Chien

    2011-01-01

    Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure. We have previously shown that cellular MRI of iron-oxide labeled immune-cell infiltration can provide a non-invasive measure of rejection status by detecting areas of hypointensity on T2*-weighted images. In the current study, we tested the feasibility of using a fluorine-based cellular tracer agent to detect m...

  16. Combined use of myeloid-related protein 8/14 and procalcitonin as diagnostic markers for acute allograft rejection in kidney transplantation recipients.

    Jung, Da-Yeon; Park, Jae Berm; Lee, Eun-Na; Lee, Hyun-Ah; Joh, Jae-Won; Kwon, Choon Hyuck; Ki, Chang-Seok; Lee, Soo-Youn; Kim, Sung-Joo

    2008-02-01

    The myeloid-related proteins 8 and 14 exist as a dimeric complex (MRP 8/14) and serve as early and highly specific markers for inflammatory processes, such as allograft rejection and non-viral (bacterial or fungal) infections. An elevated procalcitonin (PCT) concentration in serum also serves as a diagnostic indicator of non-viral infection. Therefore, by measuring both MRP 8/14 and PCT serum concentrations, one may be able to distinguish between acute allograft rejection and non-viral infections in non-rejection transplant recipients. Here, we investigated whether MRP 8/14 and PCT can function as prognostic (Study I) or diagnostic (Study II) markers for allograft rejection in renal transplant recipients. In Study I, the serum concentrations of MRP 8/14 and PCT during the first 2 weeks after transplantation did not differ between patients who did and did not suffer organ rejection within 1 year post-transplantation; these findings suggest that the MRP 8/14 and PCT parameters are not valid prognostic markers. However, in Study II, patients with acute rejection or non-rejection/non-viral infection groups displayed a significant increase in serum MRP 8/14 concentration, and non-rejection patients with non-viral infections only had elevation in the PCT serum concentrations. These results indicate that the combined use of MRP 8/14 and PCT serum concentrations can allow one to distinguish between allograft rejection and other inflammatory processes, such as infection. PMID:18158120

  17. Blockade of 4-1BB/4-1BB ligand interactions prevents acute rejection in rat liver transplantation

    QIN Lei; GUAN Hong-geng; ZHOU Xiao-jun; YIN Jun; LAN Jing; QIAN Hai-xin

    2010-01-01

    Background Blocking the 4-1BB/4-1BB ligand (4-1BBL) signal may modulate the secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play a key role in organ transplantation tolerance. The aim of this study was to investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1 BBL monoclonal antibody (mAB) in acute rejection of rat orthotopic liver transplantation. Methods The orthotopic liver transplantation model was set up, while male Lewis rats were used as liver donors and Brown-Norway rats as recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB or isotype control antibody. Groups were monitored for graft survival after transplantation. Plasma chemistry, including aspartate transaminase (AST), alanine aminotransferase (ALT), and bilirubin (BIL), was assayed. The concentrations of interleukin (IL)-2, IL-10 and interferon (IFN)- γ in plasma were also measured by enzyme-linked immunosorbent assay. Allograft histology images were collected under light microscope and electron microscope. Results Isotype antibody treated recipients exhibited elevated plasma levels of liver injury markers including AST, ALT and BIL, progressive portal and venous inflammation and cellular infiltration of the liver allografts, and a mean graft survival time (MST) of 10.9 days. Administration of anti 4-1 BBL mAB resulted in a decrease in plasma levels of liver injury markers and the concentrations of IL-2, IL-10 and IFN-γ. The histological grade of rejection on day 7 decreased and MST (17.3 days) increased substantially.Conclusions These results demonstrate that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a promising strategy to prevent progression of graft rejection by suppressing T cell-mediated immunity.

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

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

    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...

  19. Anti-interleukin-2 receptor antibodies—basiliximab and daclizumab—for the prevention of acute rejection in renal transplantation

    Junichiro Sageshima

    2009-06-01

    Full Text Available Junichiro Sageshima, Gaetano Ciancio, Linda Chen, George W Burke IIIDewitt Daughtry Family Department of Surgery, Division of Kidney and Pancreas Transplantation, The Lillian Jean Kaplan Renal Transplant Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USAAbstract: The use of antibody induction after kidney transplantation has increased from 25% to 63% in the past decade and roughly one half of the induction agent used is anti-interleukin-2 receptor antibody (IL-2RA, ie, basiliximab or daclizumab. When combined with calcineurin inhibitor (CNI-based immunosuppression, IL-2RAs have been shown to reduce the incidence of acute rejection, one of the predictors of poor graft survival, without increasing risks of infections and malignancies in kidney transplantation. For low-immunological-risk patients, IL-2RAs, as compared with lymphocyte-depleting antibodies, are equally efficacious and have better safety profiles. For high-risk patients, however, IL-2RAs may be inferior to lymphocyte-depleting antibodies for the prophylaxis of acute rejection. In an effort to reduce toxicities of other immunosuppressive medications without increasing the risk of acute rejection and chronic graft loss, IL-2RAs have often been combined with steroid- and CNI-sparing immunosuppression protocols. More data support the benefits of early steroid withdrawal with IL-2RA in low-risk patients, but preferred induction therapy for high-risk patients has yet to be determined. Although CNI-sparing protocols with IL-2RA may preserve renal function and improve long-term survival in selected patients, further studies are needed to identify those who benefit most from this strategy.Keywords: basiliximab, daclizumab, interleukin-2 receptor antagonist, kidney transplantation, monoclonal antibody

  20. Granzyme expression in fine-needle aspirates from liver allografts is increased during acute rejection

    Kuijf, M L; Kwekkeboom, Jaap; Kuijpers, Marianne A; Willems, Marc; Zondervan, Pieter E; Niesters, Hubert G M; Hop, Wim C J; Hack, C Erik; Paavonen, Timo; Höckerstedt, Krister; Tilanus, Hugo W; Lautenschlager, Irmeli; Metselaar, Herold J; Kuijf, Mark M L

    2002-01-01

    We investigated whether determination in fine-needle aspiration biopsy (FNAB) specimens of cells expressing granzymes (Grs) and Fas ligand would provide a reliable, easy, and quantitative measure of rejection activity in the transplanted liver. Retrospectively, 13 FNAB specimens obtained during clin

  1. Uninfected and cytomegalic endothelial cells in blood during cytomegalovirus infection : Effect of acute rejection

    Kas-Deelen, AM; de Maar, EF; Harmsen, MC; van Son, WJ; The, TH; Driessen, C.

    2000-01-01

    After transplantation, human cytomegalovirus (HCMV) infections can cause vascular damage to both the graft and the host. To study a possible relationship between the degree of vascular injury, clinical symptoms of HCMV infection, and transplant rejection, the appearance and numbers of endothelial ce

  2. A suspected case of plasma cell-rich acute renal transplant rejection associated with de novo donor-specific antibody.

    Yoshikawa, Mikiko; Kitamura, Ken; Ishimura, Takeshi; Hara, Shigeo; Fujisawa, Masato; Nishi, Shinichi

    2015-07-01

    A kidney transplant case with de novo donor-specific antibody showed monoclonal plasma cell infiltration into the graft with ABO incompatibility. Three years after transplantation, the patient's graft function suddenly deteriorated. Interstitial edema and the predominant infiltration of inflammatory plasma cells with kappa chain monoclonality were observed in biopsy specimens. The in situ hybridization of Epstein-Barr virus was negative and post-transplant lymphoproliferative disorder was not evident from radiological examinations. On laboratory examination, the patient had de novo donor-specific antibody for HLA-DQ. We suspected plasma cell-rich acute rejection for which methylprednisolone pulse therapy, plasma exchange, rituximab, and 15-deoxyspergualin were given. In the ensuing biopsy, the degree of plasma cell infiltration was similar to the first biopsy; however, kappa chain monoclonality relatively weakened. Owing to resistance to these treatments, intravenous immunoglobulin (IVIG) (0.5 g/kg/day) was added. The serum creatinine level gradually declined to 3.1 mg/dL; however, it increased up to 3.6 mg/dL again. In the final biopsy, the infiltrated plasma cells disappeared but severe interstitial fibrosis developed. This case showed difficulty in the diagnosis and treatment of plasma cell-rich acute rejection. A detailed consideration of this case may be helpful in understanding the clinical features and pathogenesis of this condition. PMID:26031590

  3. SPR detection of cardiac troponin T for acute myocardial infarction.

    Pawula, Maria; Altintas, Zeynep; Tothill, Ibtisam E

    2016-01-01

    A surface plasmon resonance (SPR) sensor developed for the rapid, sensitive and specific detection of cardiac troponin T (cTnT) in serum samples is reported in this work. An extensive optimisation of assay parameters was conducted to achieve optimal detection strategy. Both direct and sandwich immunoassay formats were investigated and optimised. The response obtained was enhanced further by the use of gold nanoparticles (AuNPs) conjugated to the anti-cTnT detection antibody. A regeneration method was developed to enable the reuse of the SPR sensor for multiple sample application. The SPR immunosensor showed good reproducibility for cTnT detection in the concentration range of 25-1000 ng mL(-1) and 5-400 ng mL(-1) for the direct and sandwich assays in buffer, respectively. The linear regression analysis was performed and R(2) value was found as 0.99 for both assays. In order to optimise the sensor for serum analysis, nonspecific binding of serum proteins was reduced through the use of additives in the dilution buffer. To achieve greater sensitivity, the performance of the cTnT immunosensor sandwich assay in human serum was evaluated using non-modified and AuNP modified detector antibodies. A detection limit (LOD) for the immunosensor in 50% serum was assessed as 5 ng mL(-1) cTnT for the standard sandwich assay and 0.5 ng mL(-1) cTnT when using AuNP conjugated detector antibodies with a linear dynamic range of 0.5-40 ng mL(-1). The dissociation constant was found as 3.28 × 10(-9) M using Langmuir binding model which indicates high affinity between cTnT and its antibody. The proposed SPR immunosensor has a promising potential to be developed for point-of-care testing for the early diagnosis of acute myocardial infarction (AMI). This method can also be used for the rapid detection of biomarkers in central nervous system diseases. PMID:26695335

  4. Postoperative intubation time is associated with acute kidney injury in cardiac surgical patients

    Heringlake, Matthias; Nowak, Yvonne; Schön, Julika; Trautmann, Jens; Berggreen, Astrid Ellen; Charitos, Efstratios I.; Paarmann, Hauke

    2014-01-01

    Introduction Acute kidney injury (AKI) is a frequent complication after cardiac surgery and is associated with a poor prognosis. Mechanical ventilation is an important risk factor for developing AKI in critically ill patients. Ventilation with high tidal volumes has been associated with postoperative organ dysfunction in cardiac surgical patients. No data are available about the effects of the duration of postoperative respiratory support in the immediate postoperative period on the incidence...

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

    Daniel Vitório; Alexandre Toledo Maciel

    2013-01-01

    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 foun...

  6. Acute Kidney Injury after Using Contrast during Cardiac Catheterization in Children with Heart Disease

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-01-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood ...

  7. Comparison of three early biomarkers for acute kidney injury after cardiac surgery under cardiopulmonary bypass

    Moriyama, Takahiro; Hagihara, Shintaro; Shiramomo, Toko; Nagaoka, Misaki; Iwakawa, Shohei; Kanmura, Yuichi

    2016-01-01

    Background Acute kidney injury (AKI) is a serious complication after cardiac surgery, being associated with a high mortality. We assessed three urinary biomarkers, L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and angiotensinogen, which are elevated through different mechanisms, and investigated which of these biomarkers was the earliest and most useful indicator of AKI after cardiac surgery. Methods This study was a prospective observational s...

  8. Increased incidence of acute kidney injury with aprotinin use during cardiac surgery detected with urinary NGAL

    Wagener, G.; Gubitosa, G.; Wang, S.;

    2008-01-01

    BACKGROUND: Use of aprotinin has been associated with acute kidney injury after cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel, very sensitive marker for renal injury. Urinary NGAL may be able to detect renal injury caused by aprotinin. This study determined if the...... use of aprotinin is associated with an increased incidence of acute kidney injury and increased levels of urinary NGAL. METHODS: In this prospective, observational study 369 patients undergoing cardiac surgery were enrolled. 205 patients received aprotinin and 164 received epsilon amino-caproic acid...... intraoperatively. Urinary NGAL was measured before and immediately after cardiac surgery and 3, 18 and 24 h later. The association of aprotinin use with the incidence of acute kidney injury (increase of serum creatinine >0.5 mg/dl) and NGAL levels was determined using logistic and linear regression models. RESULTS...

  9. Non-invasive imaging of acute renal allograft rejection in rats using small animal F-FDG-PET.

    Stefan Reuter

    Full Text Available BACKGROUND: At present, renal grafts are the most common solid organ transplants world-wide. Given the importance of renal transplantation and the limitation of available donor kidneys, detailed analysis of factors that affect transplant survival are important. Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection (AR is still a major risk for graft survival. Nowadays, AR can only be definitively by renal biopsy. However, biopsies carry a risk of renal transplant injury and loss. Most important, they can not be performed in patients taking anticoagulant drugs. METHODOLOGY/PRINCIPAL FINDINGS: We present a non-invasive, entirely image-based method to assess AR in an allogeneic rat renal transplantation model using small animal positron emission tomography (PET and (18F-fluorodeoxyglucose (FDG. 3 h after i.v. injection of 30 MBq FDG into adult uni-nephrectomized, allogeneically transplanted rats, tissue radioactivity of renal parenchyma was assessed in vivo by a small animal PET-scanner (post operative day (POD 1,2,4, and 7 and post mortem dissection. The mean radioactivity (cps/mm(3 tissue as well as the percent injected dose (%ID was compared between graft and native reference kidney. Results were confirmed by histological and autoradiographic analysis. Healthy rats, rats with acute CSA nephrotoxicity, with acute tubular necrosis, and syngeneically transplanted rats served as controls. FDG-uptake was significantly elevated only in allogeneic grafts from POD 1 on when compared to the native kidney (%ID graft POD 1: 0.54+/-0.06; POD 2: 0.58+/-0.12; POD 4: 0.81+/-0.06; POD 7: 0.77+/-0.1; CTR: 0.22+/-0.01, n = 3-28. Renal FDG-uptake in vivo correlated with the results obtained by micro-autoradiography and the degree of inflammatory infiltrates observed in histology. CONCLUSIONS/SIGNIFICANCE: We propose that graft FDG-PET imaging is a new option to non-invasively, specifically, early detect, and follow

  10. SODIUM BICARBONATE INFUSION: TO PREVENT CARDIAC SURGERY - ASSOCIATED ACUTE KIDNEY INJURY

    Ramesh

    2015-02-01

    Full Text Available OBJECTIVES: The incidence of cardiac surgery – associated acute kidney injury is 50% of patients and is associated with increased mortality and morbidity. This study aimed to determine if perioperative urinary and plasma alkalization with sodium bicarbonate infusion re duces the incidence of cardiac surgery – associated acute kidney injury. SETTING AND DESIGN: This study is double blind randomized control trial conducted at U N Mehta Institute of Cardiology and Research Center , India. METHOD S AND RESULT: A total of 140 pat ients scheduled to undergo elective cardiac surgery , who were at increased risk of development of cardiac surgery – associated acute kidney injury using recognized risk factors. Patients were randomly allocated to receive either sodium bicarbonate (n = 70 o r sodium chloride (n = 70 infusion , commencing at the start of anesthesia , in a dose of 4 mmol/kg over 24 hour. The primary outcome measure was the number of patients with development of CSA - AKI , defined as an increase in creatinine greater than 25% from baseline to peak value within the first three postoperative days. Significant differences among the groups in both plasma and urinary pH were achieved 6 hours after commencement of the infusion , and these changes persisted for more than 24 hours. A total o f 7 out of 70(10% patients in the sodium bicarbonate group and 16 out of 70(22.85% patients in the sodium chloride group developed acute kidney injury within the first three postoperative days with p value of 0.06 which is statistically not significant . There were also no significant differences in ventilation hours , ICU or hospital length of stay , or mortality. CONCLUSIONS: Perioperative alkalization of blood and urine using an infusion of sodium bicarbonate did not result in a decrease in the incidence of acute kidney injury in patients undergoing cardiac surgery. KEYWORDS: Acute kidney injury; Cardiac surgery; Cardiopulmonary bypass; Creatinine

  11. Serum sickness following rabbit anti-thymocyte globulin for acute vascular renal allograft rejection

    Teng, Jessie; Hoo, Xing Ning; Tan, Sven-Jean; Dwyer, Karen

    2012-01-01

    A simultaneous pancreas–kidney transplant recipient developed serum sickness manifesting with severe upper limb allodynia, arthralgia and myalgia 17 days following rabbit anti-thymocyte globulin (rATG) infusion for biopsy-proven vascular rejection. Rapid resolution of symptoms followed treatment with high-dose glucocorticoids. rATG is increasingly favoured over equine ATG in solid-organ transplantation, and although rATG has a superior safety profile, it is important to maintain a high index ...

  12. Time elapsed after transplantation influences the relationship between the number of regulatory T cells in lung allograft biopsies and subsequent acute rejection episodes

    Krustrup, Dorrit; Iversen, Martin; Martinussen, Torben;

    2014-01-01

    Background: Regulatory T lymphocytes (Tregs) play an important role in acute rejection after lung transplantation. However, the importance of the time elapsed after transplantation on the Treg response requires further investigation.We aim to evaluate the change over time in the frequency of Tregs...... in lung allograft biopsies and to assess how Tregs relate to simultaneous and subsequent acute cellular rejection. Materials and methods: A total of 258 biopsy samples obtained 0.5, 1, 3, 12 and 24. months after transplantation from 58 consecutive lung transplant patients were included. The biopsies...... were scored for acute rejection according to the ISHLT criteria (A0-A4) and immunohistochemically stained with antibodies against FoxP3. Results: There was a tendency for a decrease in the number of Tregs/mm2 with time. However, the previous levels of Tregs/mm2 did not have any significant effect on...

  13. Clinical investigation: thyroid function test abnormalities in cardiac arrest associated with acute coronary syndrome

    Iltumur, Kenan; Olmez, Gonul; Arıturk, Zuhal; Taskesen, Tuncay; Toprak, Nizamettin

    2005-01-01

    Introduction It is known that thyroid homeostasis is altered during the acute phase of cardiac arrest. However, it is not clear under what conditions, how and for how long these alterations occur. In the present study we examined thyroid function tests (TFTs) in the acute phase of cardiac arrest caused by acute coronary syndrome (ACS) and at the end of the first 2 months after the event. Method Fifty patients with cardiac arrest induced by ACS and 31 patients with acute myocardial infarction (AMI) who did not require cardioversion or cardiopulmonary resuscitation were enrolled in the study, as were 40 healthy volunteers. The patients were divided into three groups based on duration of cardiac arrest (10 min). Blood samples were collected for thyroid-stimulating hormone (TSH), tri-iodothyronine (T3), free T3, thyroxine (T4), free T4, troponin-I and creatine kinase-MB measurements. The blood samples for TFTs were taken at 72 hours and at 2 months after the acute event in the cardiac arrest and AMI groups, but only once in the control group. Results The T3 and free T3 levels at 72 hours in the cardiac arrest group were significantly lower than in both the AMI and control groups (P 0.05). At the 2-month evaluation, a dramatic improvement was observed in T3 and free T3 levels in the cardiac arrest group (P < 0.0001). In those patients whose cardiac arrest duration was in excess of 10 min, levels of T3, free T3, T4 and TSH were significantly lower than those in patients whose cardiac arrest duration was under 5 min (P < 0.001, P < 0.001, P < 0.005 and P < 0.05, respectively). Conclusion TFTs are significantly altered in cardiac arrest induced by ACS. Changes in TFTs are even more pronounced in patients with longer periods of resuscitation. The changes in the surviving patients were characterized by euthyroid sick syndrome, and this improved by 2 months in those patients who did not progress into a vegetative state. PMID:16137355

  14. Comparison of the Th1, IFN-γ secreting cells and FoxP3 expression between patients with stable graft function and acute rejection post kidney transplantation.

    Banafsheh Nazari

    2013-09-01

    Full Text Available There are limited clinical investigations identifying the percentage of T helper 1 (Th1 and T regulatory (Treg cells in stable as well as rejected kidney allografts, a concept which needs to be more studied. The aim of our study was to compare the percentage of CD4+ IFN-γ+ cells, the number of IFN-γ secreting cells and the amount of FoxP3 expression in patients with or without stable graft function, to determine the roles of these immunological factors in stable and rejected renal allografts. In this prospective study, 3 months after transplantation 30 patients who received renal transplants from unrelated living donors were enrolled and divided into two groups, 20 patients with stable graft function and 10 patients with biopsy proven acute rejection. The percentage of Th1 CD4+ IFN-γ+ cells was determined on PBMC by flow cytometry and the number of IFN-γ secreting cells by ELISPOT method. Furthermore, FoxP3 expression of PBMCs was measured by Real Time PCR method. The results of these assessments in both groups were statistically analyzed by SPSS 14.0. Our results showed that the percentage of Th1 CD4+ IFN-γ+ cells and the number of IFN-γ secreting cells were significantly higher in the patients with acute rejection in comparison to the stable graft function group (p<0.001. In addition, the level of FoxP3 gene expression was higher in the group with stable graft compared to the acute rejection group. The higher percentage of CD4+ IFN-γ+Th1 subset and number of IFN-γ secreting cells and also the lower expression of Foxp3 could prone the patients to acute rejection episode post transplantation. By these preliminary data, it is suggested that monitoring of Th1 cells post transplantation, as an immunologic marker could predict the possibility of rejection episodes.

  15. Effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation

    Jing Liu; Yi Gao; Shuan Wang; Er-Wei Sun; Yu Wang; Zhi Zhang; Yi-Qiang Shan; Shi-Zheng Zhong

    2005-01-01

    AIM: To study effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation.METHODS: Two of Wistar rats were chosen randomly for normal liver pathology control and ten of SD rats chosen randomly for liver function control as blank group (no operation). The rest of Wistar and SD rats were divided into four groups: control group (only liver transplantation),Dex group (donors receiving intraperitoneal injection of dexamethasone), SpC group (recipients receiving infusion of spleen cells of donors), Dex-SpC group (recipients receiving infusion of apoptotic spleen cells of donors),with each group except blank group, containing 10 SD rats and 10 Wistar rats, respectively. Wistar rats received liver transplantation from SD rats, in the meantime they received infusion of spleen cells of donors, which were induced by an intraperitoneal injection of dexamethasone The serum alanine transaminase (ALT), total bilirubin (T bili), liver pathological changes and survival time were analysed. Statistical analysis was carried out using SPSS 10.0 for Windows. Differences of the parametric data of ALT in means were examined by one-way ANOVA.Differences of ALT between two groups were examined by LSD. Differences of the nonparametric data of T bili in means and scores of pathology classification for acute rejection were examined by Kruskal-Willis H test. The correlations between ALT and T bili were analysed by Bivariate. Kaplan-Meier curves were used to demonstrate survival distribution. The log-rank test was used to compare the survival data.RESULTS: There were significant differences in ALT of the five groups (F= 23.164 P= 0.000), and ALT in DexSpC group was significantly higher than that in blank control, control, Dex, and SpC groups (P = 0.000), and ALT in SpC group was significantly higher than that in blank control (P = 0.000), control (P = 0.004), and Dex groups (P = 0.02). Results of

  16. Methylprednisolone-hemisuccinate and its metabolites in serum, urine and bile from two patients with acute graft rejection.

    Lawson, G J; Chakraborty, J; Tredger, J M; Baylis, E M

    1995-01-01

    Methylprednisolone-hemisuccinate (MPHS), methylprednisolone (MP), 20-alpha-hydroxy- (20 alpha HMP) and 20-beta-hydroxymethyl-prednisolone (20 beta HMP) concentrations were measured in serum, urine and bile from two liver transplant recipients who had received 1 g MPHS by a 1 h intravenous infusion for treatment of an acute rejection episode. These patients excreted similar total amounts of the dose in urine as patients with rheumatoid arthritis (historical controls) who had normal liver function. The transplant patients showed a ratio in urine of 'total metabolites'/MPHS that was one third that of patients with rheumatoid arthritis. Less than 0.2% of the administered MPHS appeared in bile as MPHS, MP, 20 alpha HMP and 20 beta HMP during the 24 h following infusion. Liver transplantation did not affect the overall elimination of drug in urine. However, the impaired liver function following transplantation resulted in reduced conversion of MPHS to its active form (MP). PMID:7742157

  17. Fiber optic probe enabled by surface-enhanced Raman scattering for early diagnosis of potential acute rejection of kidney transplant

    Chi, Jingmao; Chen, Hui; Tolias, Peter; Du, Henry

    2014-06-01

    We have explored the use of a fiber-optic probe with surface-enhanced Raman scattering (SERS) sensing modality for early, noninvasive and, rapid diagnosis of potential renal acute rejection (AR) and other renal graft dysfunction of kidney transplant patients. Multimode silica optical fiber immobilized with colloidal Ag nanoparticles at the distal end was used for SERS measurements of as-collected urine samples at 632.8 nm excitation wavelength. All patients with abnormal renal graft function (3 AR episodes and 2 graft failure episodes) who were clinically diagnosed independently show common unique SERS spectral features in the urines collected just one day after transplant. SERS-based fiber-optic probe has excellent potential to be a bedside tool for early diagnosis of kidney transplant patients for timely medical intervention of patients at high risk of transplant dysfunction.

  18. Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1

    Burton, C.M.; Iversen, M.; Carlsen, J.;

    2009-01-01

    BACKGROUND: Post-transplant baseline forced expiratory volume in 1 second (FEV(1)) constitutes a systematic bias in analyses of bronchiolitis obliterans syndrome (BOS). This retrospective study evaluates risk factors for BOS adjusting for the confounding of post-transplant baseline FEV(1). METHODS......: A multivariate survival and competing risk analysis of a large consecutive series of patients (n = 389) from a national center 1992 to 2004. Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and no available lung function measurements (n = 4). RESULTS......: The first maximum FEV(1) occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an...

  19. Correlation between antiplatelet resistance and recurrent cardiac ischemic events of patients with acute myocardial infarction

    李蕾

    2012-01-01

    Objective To evaluate the predictive value of anti-platelet resistance assessed by whole blood electronic impedance aggregometry(EIA) for the risk of recurrent cardiac ischemic events in patients with acute myocardial infarction(AMI) who underwent coronary stenting. Methods We enrolled

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

    Lewinter, Christian; Bland, John M; Crouch, Simon; Doherty, Patrick; Lewin, Robert J; Køber, Lars; Hall, Alistair S; Gale, Christopher P

    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...

  1. Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation.

    Golshayan, Déla; Wójtowicz, Agnieszka; Bibert, Stéphanie; Pyndiah, Nitisha; Manuel, Oriol; Binet, Isabelle; Buhler, Leo H; Huynh-Do, Uyen; Mueller, Thomas; Steiger, Jürg; Pascual, Manuel; Meylan, Pascal; Bochud, Pierre-Yves

    2016-04-01

    There are conflicting data on the role of the lectin pathway of complement activation and its recognition molecules in acute rejection and outcome after transplantation. To help resolve this we analyzed polymorphisms and serum levels of lectin pathway components in 710 consecutive kidney transplant recipients enrolled in the nationwide Swiss Transplant Cohort Study, together with all biopsy-proven rejection episodes and 1-year graft and patient survival. Functional mannose-binding lectin (MBL) levels were determined in serum samples, and previously described MBL2, ficolin 2, and MBL-associated serine protease 2 polymorphisms were genotyped. Low MBL serum levels and deficient MBL2 diplotypes were associated with a higher incidence of acute cellular rejection during the first year, in particular in recipients of deceased-donor kidneys. This association remained significant (hazard ratio 1.75, 95% confidence interval 1.18-2.60) in a Cox regression model after adjustment for relevant covariates. In contrast, there was no significant association with rates of antibody-mediated rejection, patient death, early graft dysfunction or loss. Thus, results in a prospective multicenter contemporary cohort suggest that MBL2 polymorphisms result in low MBL serum levels and are associated with acute cellular rejection after kidney transplantation. Since MBL deficiency is a relatively frequent trait in the normal population, our findings may lead to individual risk stratification and customized immunosuppression. PMID:26924055

  2. C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study.

    Viglietti, D; Gosset, C; Loupy, A; Deville, L; Verine, J; Zeevi, A; Glotz, D; Lefaucheur, C

    2016-05-01

    Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR. PMID:26693703

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

    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.

  4. Role of 1, 25-dihydroxyvitamin D3 in preventing acute rejection of allograft following rat orthotopic liver transplantation

    章爱斌; 郑树森; 贾长库; 王雁

    2004-01-01

    Background We investigated the role of 1, 25-dihydroxyvitamin D3 (1, 25-(OH)2D3) in preventing allograft from acute rejection following orthotopic liver transplantation. Methods A rat orthotopic liver transplantation model was used in this study. SD-Wistar rats served as a high responder strain combination. Recipients were subjected to administration of 1, 25-(OH)2 D3 at dosages ranging from 0.25 μg·kg-1*d-1 to 2.5 μg·kg-1*d-1. Survival after transplantation as well as pathological rejection grades and IFN-γ mRNA, IL-10 mRNA transcription intragraft on day 7, and day 30 post-transplantation were observed. Results After recipients were treated with 1, 25(OH)2 D3 at dosages of 0.5 μg*kg-1*d-1 or 1.0 μ g*kg-1*d-1, survivals of recipients were prolonged. Ninety-five percent confidence intervals of survival were 46-87 days and 69-102 days (both P=0.0005 vs control group), respectively. On day seven post-transplantation, relative levels of IFN-γ mRNA transcription were 0.59±0.12 and 0.49±0.16, which was higher than the control group (P=0.005, P=0.003, respectively). Relative levels of IL-10 mRNA transcription were 0.83±0.09 and 0.76±0.09, which was lower than the control group (P=0.002, P=0.003, respectively). At a dosage of 0.5 μg·kg-1*d-1, the median of pathological rejection grade on day seven and on day thirty post-transplantation were 1.5 and 2.0 in comparison with the CsA-treated group (P=0.178, P=0.171, respectively). At a dosage of 0.5 μg·kg-1*d-1, the median of pathological rejection grade on day seven and day thirty post-transplantation were 1.5 and 1.5 in comparison with CsA-treated group (P=0.350, P=0.693, respectively).Conclusion After each recipient was treated with 1,25-(OH)2 D3 at a dosage of (0.5-1.0) μg·kg-1*d-1, transcription of cytokine intragraft was accommodated effectively and deviated to Th2 type, resulting in alleviation of acute rejection. 1, 25-(OH)2 D3 can prolong survival of recipient after orthotopic liver transplantation.

  5. Acute social stress and cardiac electrical activity in rats

    Sgoifo, A; Stilli, D; de Boer, SF; Koolhaas, JM; Musso, E; Koolhaas, Jaap M.

    1998-01-01

    This paper summarizes the results of experiments aimed at describing electrocardiographic responses to different acute social stressors in healthy male rats. Electrocardiograms were telemetrically recorded during maternal aggression, social defeat, and psychosocial stimulation, as obtained using the

  6. Contrast-fluid level in the inferior vena cava (IVC niveau sign) in patients with acute type A aortic dissection. Computed tomography findings during acute cardiac tamponade

    The purpose of this study was to report a new computed tomography (CT) finding in acute cardiac tamponade: a contrast-fluid level in the hepatic inferior vena cava (IVC) during an arterial dominant phase CT study (IVC niveau sign) in patients with acute type A aortic dissection. We retrospectively reviewed CT studies with the diagnosis of proximal aortic dissection (Stanford type A) with acute cardiac tamponade. There were 12 patients enrolled in the study (6 women, 6 men; mean age 66 years). A total of 62 patients were selected as a control chronic pericardial effusion group to compare with the acute cardiac tamponade group. Among the 12 patients with acute cardiac tamponade, the IVC niveau sign was seen in 7 (58%). In the control chronic pericardial effusion group (n=62), we identified the IVC niveau sign in only one patient (1.6%). There was a significant difference in the presence of the IVC niveau sign between the acute cardiac tamponade and chronic pericardial effusion groups (P<0.0001). The presence of the IVC niveau sign suggests acute cardiac tamponade in patients with acute type A aortic dissection. (author)

  7. T2-weighted cardiovascular magnetic resonance in acute cardiac disease

    Eitel Ingo; Friedrich Matthias G

    2011-01-01

    Abstract Cardiovascular magnetic resonance (CMR) using T2-weighted sequences can visualize myocardial edema. When compared to previous protocols, newer pulse sequences with substantially improved image quality have increased its clinical utility. The assessment of myocardial edema provides useful incremental diagnostic and prognostic information in a variety of clinical settings associated with acute myocardial injury. In patients with acute chest pain, T2-weighted CMR is able to identify acu...

  8. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......: (1) primary or reactivated EBV infection (PREBV) was correlated to acute rejection (treated with OKT3; P<0.00005) and to the incidence of PTLD (P=0.03; P=0.01, if Hodgkin's disease is included); (2) aciclovir protected against PREBV (P<0.00005) and (3) adding mofetil to the immunosuppressive protocol...... immunosuppression with mofetil protects against acute rejection. In combination with aciclovir, there is also a reduction in the number of PREBVs, apparently as a result of both direct viral prophylaxis and better rejection control, and in the incidence of EBV-induced PTLD Udgivelsesdato: 1999...

  9. Resveratrol Upregulates Cardiac SDF-1 in Mice with Acute Myocardial Infarction through the Deacetylation of Cardiac p53.

    Wang Hong

    Full Text Available We previously demonstrated that resveratrol (RSV administration causes cardiac stromal cell-derived factor (SDF-1 upregulation and can enhance the mobilization of stem cells in mice with acute myocardial infarction (AMI. However, the upstream signal transduction involved in SDF-1 regulation in the setting of AMI and RSV administration remains unclear. Because RSV is a sirtuin 1 (SIRT1 activator and SIRT proteins act as deacetylases, we investigated the role of SIRT1 in SDF-1 upregulation and its subsequent effects.In vitro experiments with H9C2 cardiomyocytes under hypoxia and serum-deprivation conditions showed that p53 acted upstream of SDF-1. RSV could not regulate SDF-1 effectively after SIRT1 silencing, indicating that it is dependent on SIRT1. Subsequently, male C57BL/6 mice were divided into four groups: 1 sham, 2 MI, 3 MI+RSV, and 4 MI+RSV plus nicotinamide, an inhibitor of the deacetylase activity of SIRT (MI+RSV+NAM. Compared with the sham mice, AMI caused a slight increase in the cardiac p53 level and resulted in significant SIRT1 downregulation and p53 acetylation or activation. Compared with the MI mice, MI+RSV administration improved the cardiac SDF-1 level and reversed the reduction of SIRT1 and the activation of p53. Furthermore, we observed less cardiac dysfunction in MI+RSV mice and determined that NAM abolished the effects of RSV.RSV enhances cardiac SDF-1 excretion after AMI partially through a SIRT1 normalization/p53 inactivation pathway.

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

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

    2012-03-01

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