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Sample records for acute rejection rates

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

    PubMed Central

    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

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

    PubMed Central

    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 analyzed demographics, immunosuppression, rejection, infection and graft and patient survival rates. Results: Late acute rejection in liver transplantation showed poor results mainly regarding patient and graft survival. Almost all of these cohort studies were retrospective and descriptive. The incidence of late acute rejection varied from 7-40% in these studies. Late acute rejection was one cause for graft loss and resulted in different outcomes with worse patient and graft survival after liver transplant. Late acute rejection has been variably defined and may be a cause of chronic rejection with worse prognosis. Late acute rejection occurs during a period in which the goal is to maintain lower immunosuppression after liver transplantation. Conclusion: The current articles show the importance of late acute rejection. The real benefit is based on early diagnosis and adequate treatment at the onset until late follow up after liver transplantation. PMID:26537150

  3. Renal graft irradiation in acute rejection

    SciTech Connect

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

    1983-03-01

    To evaluate the effect of graft irradiation in the treatment of acute rejection of renal transplants, a randomized study was conducted from 1978 to 1981. Patients with acute rejection were given standard medical management in the form of intravenous methylprednisolone, and were chosen randomly to receive either graft irradiation (175 rads every other day, to a total of 525 rads) or simulated (sham) irradiation. Eighty-three rejections occurring in 64 grafts were randomized to the protocol. Rejection reversal was recorded in 84.5% of control grafts and 75% of the irradiated grafts. Recurrent rejections were more frequent and graft survival was significantly lower in the irradiated group (22%) than in the control group (54%). Graft irradiation does not appear to be beneficial in the treatment of acute rejection of renal transplants when used in conjunction with high-dose steroids.

  4. The biology of acute transplant rejection.

    PubMed Central

    Tilney, N L; Kupiec-Weglinski, J W

    1991-01-01

    An intriguing and increasingly understood facet of immune responses is the ability of a recipient to destroy a foreign tissue or organ graft. The phenomenon of acute rejection of an allograft involves a series of complex and inter-related cellular and humoral events, culminating in graft death. Some of the current thinking surrounding this phenomenon is reviewed. PMID:1867525

  5. Disparate rates of acute rejection and donor-specific antibodies among high-immunologic risk renal transplant subgroups receiving antithymocyte globulin induction.

    PubMed

    Patel, Samir J; Suki, Wadi N; Loucks-DeVos, Jennifer; Graviss, Edward A; Nguyen, Duc T; Knight, Richard J; Kuten, Samantha A; Moore, Linda W; Teeter, Larry D; Gaber, Lillian W; Gaber, A Osama

    2016-08-01

    Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups. PMID:27196395

  6. Imaging-based diagnosis of acute renal allograft rejection

    PubMed Central

    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

  7. Prediction of acute cardiac rejection by changes in left ventricular volumes

    SciTech Connect

    Novitzky, D.; Cooper, D.K.; Boniaszczuk, J.

    1988-11-01

    Sixteen patients underwent heart transplantation (11 orthotopic, five heterotopic). Monitoring for acute rejection was by both endomyocardial biopsy (EMB) and multigated equilibrium blood pool scanning with technetium 99m-labelled red blood cells. From the scans information was obtained on left ventricular volumes (stroke, end-diastolic, and end-systolic), ejection fraction, and heart rate. Studies (208) were made in the 16 patients. There was a highly significant correlation between the reduction in stroke volume and end-diastolic volume (and a less significant correlation in end-systolic volume) and increasing acute rejection seen on EMB. Heart rate and ejection fraction did not correlate with the development of acute rejection. Correlation of a combination of changes in stroke volume and end-diastolic volume with EMB showed a sensitivity of 85% and a specificity of 96%. Radionuclide scanning is therefore a useful noninvasive tool for monitoring acute rejection.

  8. Expression of Tumor Necrosis Factor in Human Acute Cardiac Rejection

    PubMed Central

    Arbustini, Eloisa; Grasso, Maurizia; Diegoli, Marta; Bramerio, Manuela; Foglieni, Andrea Scotti; Albertario, Marco; Martinelli, Luigi; Gavazzi, Antonello; Goggi, Claudio; Campana, Carlo; Vigano, Mario

    1991-01-01

    The authors performed an immunohistochemical study on expression of tumor necrosis factor alpha (TNFα) in endomyocardial biopsies from human cardiac allografts. TNFα immunoreactivity was found in 45% biopsies with mild acute rejection, in 83% biopsies with focal moderate rejection, in 80% biopsies with diffuse moderate rejection. Biopsies with absent rejection did not show immunoreactive cells. In mild rejection, positive cells were few and scanty monocytes and macrophages (MAC-387 and LN5 positive cells) and T lymphocytes (UCHL-1/CD45 RO positive cells) (up to 20% of all infiltrating cells). Expression of major histocompatibility complex (MHC) class II antigens on infiltrating and endothelial cells occurred earlier and independent of TNFα reactivity. Number of immunoreactive cells increased in moderate rejection (up to 50%). Immunoreactivity was also present in nonpigmented macrophages in part of the biopsies with resolving rejection (45%). The authors conclude that TNFα is expressed in acute cardiac rejection by immunologically activated inflammatory cells. Immunoreactive cells increase in number with increasing severity of the reaction. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:1928295

  9. Early diagnosis of acute postoperative renal transplant rejection

    SciTech Connect

    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.

  10. Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection.

    PubMed

    Cui, Ye; Liu, Kaifeng; Monzon-Medina, Maria E; Padera, Robert F; Wang, Hao; George, Gautam; Toprak, Demet; Abdelnour, Elie; D'Agostino, Emmanuel; Goldberg, Hilary J; Perrella, Mark A; Forteza, Rosanna Malbran; Rosas, Ivan O; Visner, Gary; El-Chemaly, Souheil

    2015-11-01

    Lung transplantation is the only viable option for patients suffering from otherwise incurable end-stage pulmonary diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Despite aggressive immunosuppression, acute rejection of the lung allograft occurs in over half of transplant recipients, and the factors that promote lung acceptance are poorly understood. The contribution of lymphatic vessels to transplant pathophysiology remains controversial, and data that directly address the exact roles of lymphatic vessels in lung allograft function and survival are limited. Here, we have shown that there is a marked decline in the density of lymphatic vessels, accompanied by accumulation of low-MW hyaluronan (HA) in mouse orthotopic allografts undergoing rejection. We found that stimulation of lymphangiogenesis with VEGF-C156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection response and improves clearance of HA from the lung allograft. Longitudinal analysis of transbronchial biopsies from human lung transplant recipients demonstrated an association between resolution of acute lung rejection and decreased HA in the graft tissue. Taken together, these results indicate that lymphatic vessel formation after lung transplantation mediates HA drainage and suggest that treatments to stimulate lymphangiogenesis have promise for improving graft outcomes. PMID:26485284

  11. Blocking MHC class II on human endothelium mitigates acute rejection

    PubMed Central

    Abrahimi, Parwiz; Qin, Lingfeng; Chang, William G.; Bothwell, Alfred L.M.; Tellides, George; Saltzman, W. Mark; Pober, Jordan S.

    2016-01-01

    Acute allograft rejection is mediated by host CD8+ cytotoxic T lymphocytes (CTL) targeting graft class I major histocompatibility complex (MHC) molecules. In experimental rodent models, rejection requires differentiation of naive CD8+ T cells into alloreactive CTL within secondary lymphoid organs, whereas in humans, CTL may alternatively develop within the graft from circulating CD8+ effector memory T cells (TEM) that recognize class I MHC molecules on graft endothelial cells (EC). This latter pathway is poorly understood. Here, we show that host CD4+ TEM, activated by EC class II MHC molecules, provide critical help for this process. First, blocking HLA-DR on EC lining human artery grafts in immunodeficient mice reduces CD8+ CTL development within and acute rejection of the artery by adoptively transferred allogeneic human lymphocytes. Second, siRNA knockdown or CRISPR/Cas9 ablation of class II MHC molecules on EC prevents CD4+ TEM from helping CD8+ TEM to develop into CTL in vitro. Finally, implanted synthetic microvessels, formed from CRISPR/Cas9-modified EC lacking class II MHC molecules, are significantly protected from CD8+ T cell–mediated destruction in vivo. We conclude that human CD8+ TEM–mediated rejection targeting graft EC class I MHC molecules requires help from CD4+ TEM cells activated by recognition of class II MHC molecules. PMID:26900601

  12. Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection

    PubMed Central

    Cui, Ye; Liu, Kaifeng; Monzon-Medina, Maria E.; Padera, Robert F.; Wang, Hao; George, Gautam; Toprak, Demet; Abdelnour, Elie; D’Agostino, Emmanuel; Goldberg, Hilary J.; Perrella, Mark A.; Forteza, Rosanna Malbran; Rosas, Ivan O.; Visner, Gary; El-Chemaly, Souheil

    2015-01-01

    Lung transplantation is the only viable option for patients suffering from otherwise incurable end-stage pulmonary diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Despite aggressive immunosuppression, acute rejection of the lung allograft occurs in over half of transplant recipients, and the factors that promote lung acceptance are poorly understood. The contribution of lymphatic vessels to transplant pathophysiology remains controversial, and data that directly address the exact roles of lymphatic vessels in lung allograft function and survival are limited. Here, we have shown that there is a marked decline in the density of lymphatic vessels, accompanied by accumulation of low-MW hyaluronan (HA) in mouse orthotopic allografts undergoing rejection. We found that stimulation of lymphangiogenesis with VEGF-C156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection response and improves clearance of HA from the lung allograft. Longitudinal analysis of transbronchial biopsies from human lung transplant recipients demonstrated an association between resolution of acute lung rejection and decreased HA in the graft tissue. Taken together, these results indicate that lymphatic vessel formation after lung transplantation mediates HA drainage and suggest that treatments to stimulate lymphangiogenesis have promise for improving graft outcomes. PMID:26485284

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

    PubMed Central

    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

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

    PubMed

    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

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

    SciTech Connect

    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

  16. Serum metabolomics study of the acute graft rejection in human renal transplantation based on liquid chromatography-mass spectrometry.

    PubMed

    Zhao, Xinjie; Chen, Jihong; Ye, Lei; Xu, Guowang

    2014-05-01

    Acute graft rejection is one of the most common and serious postcomplications in renal transplantation. A noninvasive method is needed to specifically monitor acute graft rejection. We investigated metabolic alterations of acute graft rejection in human renal transplantation by applying a metabolomics approach. Sera from 11 acute graft rejection subjects and 16 nonacute graft rejection subjects were analyzed by a nontargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach including both hydrophilic interaction chromatography and reversed-phase liquid chromatography separations. Discriminative metabolites of acute graft rejection after transplantation were detected, including creatinine, kynurenine, uric acid, polyunsaturated fatty acid, phosphatidylcholines, sphingomyelins, lysophosphatidylcholines, etc. The lower level of serum dehydroepiandrosterone sulfate was found in the acute graft rejection group before transplantation. The results revealed comprehensive metabolic abnormalities in acute graft rejection. The findings are valuable for the clinic noninvasive diagnosis or therapy of acute graft rejection. PMID:24641727

  17. Monocytic Tissue Transglutaminase in a Rat Model for Reversible Acute Rejection and Chronic Renal Allograft Injury

    PubMed Central

    Zakrzewicz, Anna; Atanasova, Srebrena; Padberg, Winfried

    2015-01-01

    Acute rejection is a major risk factor for chronic allograft injury (CAI). Blood leukocytes interacting with allograft endothelial cells during acute rejection were suggested to contribute to the still enigmatic pathogenesis of CAI. We hypothesize that tissue transglutaminase (Tgm2), a multifunctional protein and established marker of M2 macrophages, is involved in acute and chronic graft rejection. We focus on leukocytes accumulating in blood vessels of rat renal allografts (Fischer-344 to Lewis), an established model for reversible acute rejection and CAI. Monocytes in graft blood vessels overexpress Tgm2 when acute rejection peaks on day 9 after transplantation. Concomitantly, caspase-3 is activated, suggesting that Tgm2 expression is linked to apoptosis. After resolution of acute rejection on day 42, leukocytic Tgm2 levels are lower and activated caspase-3 does not differ among isografts and allografts. Cystamine was applied for 4 weeks after transplantation to inhibit extracellular transglutaminase activity, which did, however, not reduce CAI in the long run. In conclusion, this is the first report on Tgm2 expression by monocytes in vivo. Tgm2 may be involved in leukocytic apoptosis and thus in reversion of acute rejection. However, our data do not support a role of extracellular transglutaminase activity as a factor triggering CAI during self-limiting acute rejection. PMID:26063971

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

    PubMed Central

    Pawelski, Helga; Schnöckel, Uta; Kentrup, Dominik; Grabner, Alexander; Schäfers, Michael; Reuter, Stefan

    2014-01-01

    Molecular imaging techniques such as single 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. PMID:24804257

  19. Acute allograft rejection and immunosuppression: influence on endogenous melatonin secretion.

    PubMed

    Cardell, Markus; Jung, Florian Johannes; Zhai, Wei; Hillinger, Sven; Welp, Andre; Manz, Bernhard; Weder, Walter; Korom, Stephan

    2008-04-01

    Melatonin displays a dose-dependent immunoregulatory effect in vitro and in vivo. Exogenous high-dose melatonin therapy exerted an immunosuppressive effect, abrogating acute rejection (AR), significantly prolonging transplant survival. Endogenous melatonin secretion, in response to heterotopic rat cardiac allograft transplantation (Tx), was investigated during the AR response and under standardized immunosuppressive maintenance therapy with cyclosporin A (CsA) and rapamycin (RPM). Recipients of syngeneic transplants, and recipients of allogeneic grafts, either untreated or receiving immunosuppressive therapy constituted the experimental groups. Endogenous circadian melatonin levels were measured at 07:00, 19:00, and 24:00 hr, using a novel radioimmunoassay (RIA) procedure, under standardized 12-hr-light/dark-conditions (light off: 19:00 hr; light on: 07:00 hr), before and after Tx. Neither the operative trauma, nor the challenge with a perfused allograft or the AR response influenced endogenous melatonin peak secretion. Immunosuppressive therapy with CsA led to a significant increase in peak secretion, measured for days 7 (212 +/- 40.7 pg/mL; P < 0.05), 14 (255 +/- 13.9 pg/mL; P < 0.001), and 21 (219 +/- 34 pg/mL; P < 0.01) after Tx, as compared with naïve animals (155 +/- 25.8 pg/mL). In contrast, treatment with RPM significantly decreased the melatonin peak post-Tx up to day 7 (87 +/- 25.2 pg/mL; P < 0.001), compared with naïve animals (155 +/- 25.8 pg/mL). These findings imply a robust nature of the endogenous circadian melatonin secretion kinetics, even against the background of profound allogeneic stimuli. Immunosuppressive maintenance therapy with CsA and RPM modulated early melatonin secretion, indicating a specific secondary action of these drugs. Further studies are necessary to disclose the long-term effect of immunosuppressive therapy on circadian melatonin secretion in transplant recipients. PMID:18339121

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

    SciTech Connect

    Atkins, H.L.; Oster, Z.H.; Anaise, D.; Wein, S.; Waltzer, W.; Gonder, A.; Cooch, E.; Rapaport, F.T.

    1985-05-01

    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.

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

    PubMed Central

    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

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

    PubMed

    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

  3. 15 CFR 700.13 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Acceptance and rejection of rated... and rejection of rated orders. (a) Mandatory acceptance. (1) Except as otherwise specified in this... for comparable unrated orders. (b) Mandatory rejection. Unless otherwise directed by Commerce: (1)...

  4. The Complex Role of iNOS in Acutely-Rejecting Cardiac Transplants

    PubMed Central

    Pieper, Galen M.; Roza, Allan M.

    2008-01-01

    This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutely-rejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed. PMID:18291116

  5. Alteration in systemic vascular resistance and cardiac output during acute cellular rejection and recovery in heart transplant recipients.

    PubMed

    Garan, Arthur R; Uriel, Nir; Sayer, Gabriel; Sims, Daniel; Zahner, Doris; Farr, Maryjane; Mancini, Donna; Jorde, Ulrich P

    2010-03-01

    Coronary vascular reserve is impaired during acute cellular rejection of the orthotopically transplanted heart, but changes in the peripheral vasculature during rejection have not been well described. To investigate whether peripheral vascular compensatory mechanisms are preserved after orthotopic heart transplantation (OHT), we longitudinally observed systemic vascular resistance (SVR) and cardiac output (CO) during acute cellular rejection. CO decreased during high-grade acute cellular rejection, and maintenance of mean arterial pressure was achieved by increases in SVR, and these changes did not return to baseline until several months after histologic resolution of rejection. PMID:19875310

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

    PubMed

    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

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

    PubMed

    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

  8. The effect of cytomegalovirus infection on acute rejection in kidney transplanted patients

    PubMed Central

    Hasanzamani, Boshra; Hami, Maryam; Zolfaghari, Vajihe; Torkamani, Mahtab; Ghorban Sabagh, Mahin; Ahmadi Simab, Saiideh

    2016-01-01

    Introduction: It is known that cytomegalovirus (CMV) infection is a common problem among kidney transplant patients. This infection can be increased morbidity and decreased graft survival. This problem has been associated with acute rejection too. Patients and Methods: One hundred and thirty renal transplant patients were included in a prospective, case-control study. The renal transplant patients were divided into two groups; patients group with CMV infection and control group without CMV infection. Serum CMV-IgG in all patients was positive (donor and recipients). None of patients had received anti-thymocyte-globulin and thymoglobulin. CMV infection was diagnosed by quantitative CMV-PCR (polymerase chain reaction) test (more than 500 copies/μg). Rejection episode was defined by kidney isotope scan or biopsy. Results: In the group of 66 CMV infection patients (41 male [62.1%] and 25 female [37.9%]) the incidence of graft rejection was 36%, however in the group of 64 control patients the incidence of graft rejection was 9.4 % (P < 0.005). Conclusion: CMV infection is important predisposing factor for acute allograft rejection after kidney transplantation. The results of this study suggests that the control of CMV infection could decrease episodes of acute kidney rejection. PMID:27471740

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

    PubMed Central

    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

  10. Acute renal transplant rejection in children: assessment by Duplex Doppler sonography.

    PubMed

    Vergesslich, K A; Khoss, A E; Balzar, E; Schwaighofer, B; Ponhold, W

    1988-01-01

    Over a two year period 74 consecutive Duplex Doppler scans were performed in 23 children with renal allografts and were compared to the Doppler sonographic findings in orthotopic kidneys of 25 age matched healthy controls. The Doppler waveforms of renal arterial flow were analyzed qualitatively assessing systolic and diastolic flow amplitudes, for quantitation the Pourcelot index (PI) was used. There was no variation between the Doppler waveforms in recipients with normal allograft function and healthy controls. In 12 patients with biopsy proven acute rejection a decrease or absence of the diastolic flow amplitude was noted, resulting in increased pulsatility of the Doppler waveform. The mean PI in acute rejection differed significantly from the mean PI in normal allograft function. Duplex Doppler sonography is a useful imaging modality in the differentiation between acute rejection and normal allograft function and should therefore be integrated in the screening of children after renal transplantation. PMID:3054768

  11. Insights from computational modeling in inflammation and acute rejection in limb transplantation.

    PubMed

    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 multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection. PMID:24926998

  12. Expanding the antibody-mediated component of plasma cell-rich acute rejection: A case series

    PubMed Central

    Uppin, M. S.; Gudithi, S.; Taduri, G.; Prayaga, A. K.; Raju, S. B.

    2016-01-01

    Renal allograft rejection is mediated by T-cells (T-cell mediated rejection) or by donor-specific antibodies (DSAs) (antibody mediated rejection, ABMR). Plasma cell-rich acute rejection (PCAR) is a unique entity due to its peculiar morphology and poor prognostic behavior. All allograft biopsies done at our center from January 2013 to October 2014 were reviewed, and seven were identified with a diagnosis of PCAR with antibody mediated rejection (ABMR). The allograft biopsies were classified as per the Banff 2007 schema. Immunohistochemistry with C4d, SV 40, CD3, CD20, CD138, kappa and lambda light chain was performed. Total 210 allograft biopsies were performed in the study period of which seven biopsies (3.3%) were diagnosed as PCAR with ABMR. All these were late ABMRs (more than 6 months) with median posttransplant duration of 17 months. The allograft biopsy showed features of PCAR along with glomerulitis, peritubular capillaritis, and positive C4d. DSA was positive in six patients. All the patients were treated with standard therapeutic measures of acute cellular rejection (ACR) and ABMR including steroids, plasma exchange, rituximab and intravenous immunoglobulins. All the patients had persistent graft dysfunction or graft loss on follow-up. PMID:27194831

  13. 19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells.

    PubMed

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

    2011-04-01

    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 magnetic resonance imaging (MRI) of iron-oxide labeled immune-cell infiltration can provide a noninvasive measure of rejection status by detecting areas of hypointensity on T 2*-weighted images. In this study, we tested the feasibility of using a fluorine-based cellular tracer agent to detect macrophage accumulation in rodent models of acute allograft rejection by fluorine-19 ((19) F) MRI and magnetic resonance spectroscopy. This study used two rat models of acute rejection, including abdominal heterotopic cardiac transplant and orthotopic kidney transplant models. Following in vivo labeling of monocytes and macrophages with a commercially available agent containing perfluoro-15-crown-5-ether, we observed (19) F-signal intensity in the organs experiencing rejection by (19) F MRI, and conventional (1) H MRI was used for anatomical context. Immunofluorescence and histology confirmed macrophage labeling. These results are consistent with our previous studies and show the complementary nature of the two cellular imaging techniques. With no background signal, (19) F MRI/magnetic resonance spectroscopy can provide unambiguous detection of fluorine labeled cells, and may be a useful technique for detecting and quantifying rejection grade in patients. PMID:21305593

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

    PubMed Central

    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

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

    PubMed

    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. PMID:26609794

  16. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation

    PubMed Central

    Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A.; Gong, Yongquan; Fischbein, Michael P.; Robbins, Robert C.; Naesens, Maarten

    2013-01-01

    Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design. PMID:24127489

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

    PubMed Central

    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

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

    PubMed Central

    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

  19. IL-15 is decreased upon CsA and FK506 treatment of acute rejection following heart transplantation in mice

    PubMed Central

    YU, ZHIYONG; ZHOU, XIAOPING; YU, SONGFENG; XIE, HAIYANG; ZHENG, SHUSEN

    2015-01-01

    The aim of this study was to investigate the effect of cyclosporine A (CsA) and tacrolimus (FK506) on interleukin-15 (IL-15) production during acute rejection following heart transplantation in mice. Inbred male Balb/c (H-2d) and C57BL/6 (H-2b) mice were used to establish a heterotopic intra-abdominal cardiac transplantation model. The mice were divided in four groups: syngeneic control, allogeneic acute rejection, allogeneic rejection treated with CsA, and allogeneic rejection treated with FK506. The expression of IL-15, IL-2, and tumor necrosis factor-α (TNF-α) was measured using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. A low level of IL-15 was detected in transplanted hearts of the control group, with a significant increase observed in the allogeneic acute rejection group. Compared to the allogeneic acute rejection group, IL-15 expression was significantly decreased in the CsA-and FK506-treated allogeneic rejection groups. The TNF-α expression pattern was similar to that of IL-15 in all groups. IL-2 expression was increased in the allogeneic acute rejection group and was inhibited in mice treated with CsA and FK506. In conclusion, increased IL-15 expression in rejected murine heart grafts may be reduced by CsA and FK506 in vivo. PMID:25333459

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

    PubMed Central

    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

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

    PubMed Central

    Wang, Jun; 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 mediate TNFR2 induction in acute cellular rejection and clear cell renal carcinoma and its contribution to these conditions and discusses its therapeutic implications. A greater understanding of the function of TNFR2 may lead to the development of new anti-TNF drugs. PMID:24350291

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

    PubMed

    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

  3. Sirt1-Positive Lymphocytes in Acute Cellular Cardiac Allograft Rejection: Contributor to Pathogenesis and a Therapeutic Target.

    PubMed

    Welsh, Kerry J; Zhao, Bihong; Buja, L Maximilian; Brown, Robert E

    2016-01-01

    Cardiac allograft rejection remains a problem, despite advances with immunosuppressants. Understanding the mechanisms behind rejection is essential for developing targeted therapies. The goal of this investigation is to explore Sirtuin 1 (Sirt1) as a therapeutic target for cardiac allograft rejection. Thirteen endomyocardial biopsy specimens with acute cellular rejection (grade 2R or 3R) were selected. CD3, CD4, CD8, CD20, CD68, T-cell intracytoplasmic antigen (TIA-1), and Sirt1 expressions were determined by immunohistochemical stains. Comparison of Sirt1 expression was made with 10 cases of grade 0R and grade 1R. Quantitative image analysis was performed. There were 2 cases of grade 3R and 11 cases of grade 2R acute cellular rejection. Sirtuin 1 expression was present in the majority of mononuclear cells (median percentage, 73.5; interquartile range, 51.2-100%); staining was also observed in cardiomyocytes. Twelve of the 13 cases (92.3%) had an elevated CD8/FoxP3 ratio, coinciding with acute cellular rejection. Sirtuin 1 expression in the nuclei of FoxP3+ cells can lead to deacetylation and inactivation of FoxP3 rendering the T-suppressor cells inactive and promoting acute cellular rejection. The use of a Sirt1 inhibitor may be a therapeutic option in expanding the functionality of the FoxP3+ T-suppressor cells and moderating the severity of such rejection. PMID:26771391

  4. Nitric oxide formation in acutely rejecting cardiac allografts correlates with GTP cyclohydrolase I activity

    PubMed Central

    2005-01-01

    Inducible nitric oxide synthase (iNOS) is a prominent component of the complex array of mediators in acute graft rejection. While NO production is determined by iNOS expression, BH4 (tetrahydrobiopterin), a cofactor of iNOS synthesized by GTP cyclohydrolase I, has been considered critical in sustaining NO production. In the present study, we examined time-dependent changes in iNOS and GTP cyclohydrolase I in rat cardiac allografts. The increase in iNOS protein and mRNA in allografts was similar at POD4 (post-operative day 4) and POD6. However, the peak increase in intragraft NO level at POD4 was not sustained at POD6. This disparity could not be explained by any decrease in iNOS enzyme activity measured ex vivo with optimal amounts of substrate and cofactors. Lower iNOS activity could be explained by changes in total biopterin levels in allografts at POD4 that was decreased to baseline at POD6. Changes in biopterin production correlated with lower GTP cyclohydrolase I protein levels but not by any change in GTP cyclohydrolase I mRNA. Functionally, allografts displayed bradycardia and distended diastolic and systolic dimensions at POD6 but not at POD4. Likewise, histological rejection scores were increased at POD4 but with a secondary increased stage at POD6. It is hypothesized that the dissimilar amounts of NO at early and later stages of rejection is due to uncoupling of iNOS arising from disproportionate synthesis of BH4. These findings provide insight into a potential pathway regulating NO bioactivity in graft rejection. Such knowledge may potentially assist in the design of newer strategies to prevent acute graft rejection. PMID:16000090

  5. The effect of pravastatin on acute rejection after kidney transplantation--a pilot study.

    PubMed

    Katznelson, S; Wilkinson, A H; Kobashigawa, J A; Wang, X M; Chia, D; Ozawa, M; Zhong, H P; Hirata, M; Cohen, A H; Teraski, P I

    1996-05-27

    Hyperlipidemia is an important complication of kidney transplantation affecting up to 74% of recipients. HMG-CoA reductase inhibitors are reported to provide safe and effective treatment for this problem. A recent study suggests that pravastatin, an HMG-CoA reductase inhibitor, also decreases the incidence of both clinically severe acute rejection episodes and natural killer cell cytotoxicity after orthotopic heart transplantation. We have performed a prospective randomized pilot study of the effect of pravastatin on these same parameters after cadaveric kidney transplantation. Graft recipients were randomized to receive pravastatin after transplantation or no pravastatin (24 patients in each group) in addition to routine cyclosporine and prednisone immunosuppression. Lipid levels, acute rejection episodes and serial natural killer cell cytotoxicities were followed for 4 months after the transplant. At the end of the study period, pravastatin had successfully controlled mean total cholesterol levels (202.6 +/- 9.3 vs. 236.5 +/- 11.9 mg/dl, P < 0.02), LDL levels (107.9 +/- 6.6 vs.149.6 +/- 10.7 mg/dl, P < 0.002), and triglyceride levels (118.8 +/- 14.2 vs. 157.2 +/- 13.8 mg/dl, P < 0.05). In addition, the pravastatin-treated group experienced a reduction in the incidence of biopsy-proven acute rejection episodes (25% vs. 58%, P = 0.01), the incidence of multiple rejections episodes (P < 0.05), and the use of both pulse methylprednisolone (P = 0.01) and OKT3 (P = 0.02). Mean natural killer cell cytotoxicity was similarly reduced (11.3 +/- 1.6 vs. 20.0 +/- 2.0% lysis of K562 target cells, P < 0.002). These data suggest that pravastatin exerts an additional immunosuppressive effect in kidney transplant recipients treated with cyclosporine-based immunosuppression. PMID:8633373

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

    PubMed Central

    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

  7. Effect of adopting a new histological grading system of acute rejection after heart transplantation

    PubMed Central

    Balk, A.; Zondervan, P.; van der Meer, P.; van Gelder, T.; Mochtar, B.; Simoons, M.; Weimar, W.

    1997-01-01

    Background—Treatment policy of acute rejection after heart transplantation has been changed after adopting the ISHLT endomyocardial biopsy grading system in 1991.
Objective—To determine the effect of this policy change on clinical outcome after transplantation.
Methods—The outcome of 147 patients who had a transplant before (early group, median follow up 96 months) and 114 patients who had a transplant after (late group, median follow up 41 months) the introduction of the ISHLT biopsy grading system was studied retrospectively. Initially "moderate rejection" according to Billingham's conventional criteria was treated. From January 1991 grade 3A and higher was considered to require intensification of immunosuppression.
Results—There were some differences between the two groups: recipients (50 v 44 years) as well as donors (28 v 24 years) were older in the "late group" and more patients of this group received early anti-T cell prophylaxis (92% v 56%). Despite more extensive use of early prophylaxis more rejection episodes were diagnosed (2.4 v 1.4) and considerably more courses of rejection treatment were instituted in the late compared with the early group (3.2 v 1.5). There were no deaths because of rejection in the late group, however, more infections occurred within the first year (mean 1.8 v 1.4) and more non-skin malignancies within the first 41 months were diagnosed (8 of 57 v 6 of 147, 95% CIs of difference includes 0). The incidence of graft vascular disease in the late group has been comparable to the early group until now. 
Conclusion—The interpretation of the ISHLT grading system resulted in lowering of the threshold for the diagnosis of rejection thereby increasing the number of rejections and subsequently the immunosuppressive load and its complications.

 Keywords: transplantation;  biopsy grading system;  rejection PMID:9470880

  8. 10 CFR 217.33 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... directed by the Department of Energy for a rated order involving all forms of energy: (1) A person shall... directed by the Department of Energy for a rated order involving all forms of energy, rated orders may be... 10 Energy 3 2014-01-01 2014-01-01 false Acceptance and rejection of rated orders. 217.33...

  9. African-American Race Modifies the Influence of Tacrolimus Concentrations on Acute Rejection and Toxicity in Kidney Transplant Recipients

    PubMed Central

    Taber, David J.; Gebregziabher, Mulugeta G.; Srinivas, Titte R.; Chavin, Kenneth D.; Baliga, Prabhakar K.; Egede, Leonard E.

    2015-01-01

    STUDY OBJECTIVE To determine the effect of tacrolimus trough concentrations on clinical outcomes in kidney transplantation, while assessing if African-American (AA) race modifies these associations. DESIGN Retrospective longitudinal cohort study of solitary adult kidney transplants. SETTING Large tertiary care transplant center. PATIENTS Adult solitary kidney transplant recipients (n=1078) who were AA (n=567) or non-AA (n =511). EXPOSURE Mean and regressed slope of tacrolimus trough concentrations. Subtherapeutic concentrations were lower than 8 ng/ml. MEASUREMENTS AND MAIN RESULTS AA patients were 1.7 times less likely than non-AA patients to achieve therapeutic tacrolimus concentrations (8 ng/ml or higher) during the first year after kidney transplant (35% vs 21%, respectively, p<0.001). AAs not achieving therapeutic concentrations were 2.4 times more likely to have acute cellular rejection (ACR) as compared with AAs achieving therapeutic concentrations (20.8% vs 8.5%, respectively, p<0.01) and 2.5 times more likely to have antibody-mediated rejection (AMR; 8.9% vs 3.6%, respectively, p<0.01). Rates of ACR (8.3% vs 6.7%) and AMR (2.0% vs 0.9% p=0.131) were similar in non-AAs compared across tacrolimus concentration groups. Multivariate modeling confirmed these findings and demonstrated that AAs with low tacrolimus exposure experienced a mild protective effect for the development of interstitial fibrosis/ tubular atrophy (IF/TA; hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.47–1.32) with the opposite demonstrated in non-AAs (HR 2.2, 95% CI 0.90–5.1). CONCLUSION In contradistinction to non-AAs, AAs who achieve therapeutic tacrolimus concentrations have substantially lower acute rejection rates but are at risk of developing IF/TA. These findings may reflect modifiable time-dependent racial differences in the concentration-effect relationship of tacrolimus. Achievement of therapeutic tacrolimus trough concentrations, potentially through genotyping and

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

    PubMed Central

    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

  11. Clinical biochemistry laboratory rejection rates due to various types of preanalytical errors

    PubMed Central

    Atay, Aysenur; Demir, Leyla; Cuhadar, Serap; Saglam, Gulcan; Unal, Hulya; Aksun, Saliha; Arslan, Banu; Ozkan, Asuman; Sutcu, Recep

    2014-01-01

    Introduction: Preanalytical errors, along the process from the beginning of test requests to the admissions of the specimens to the laboratory, cause the rejection of samples. The aim of this study was to better explain the reasons of rejected samples, regarding to their rates in certain test groups in our laboratory. Materials and methods: This preliminary study was designed on the rejected samples in one-year period, based on the rates and types of inappropriateness. Test requests and blood samples of clinical chemistry, immunoassay, hematology, glycated hemoglobin, coagulation and erythrocyte sedimentation rate test units were evaluated. Types of inappropriateness were evaluated as follows: improperly labelled samples, hemolysed, clotted specimen, insufficient volume of specimen and total request errors. Results: A total of 5,183,582 test requests from 1,035,743 blood collection tubes were considered. The total rejection rate was 0.65 %. The rejection rate of coagulation group was significantly higher (2.28%) than the other test groups (P < 0.001) including insufficient volume of specimen error rate as 1.38%. Rejection rates of hemolysis, clotted specimen and insufficient volume of sample error were found to be 8%, 24% and 34%, respectively. Total request errors, particularly, for unintelligible requests were 32% of the total for inpatients. Conclusions: The errors were especially attributable to unintelligible requests of inappropriate test requests, improperly labelled samples for inpatients and blood drawing errors especially due to insufficient volume of specimens in a coagulation test group. Further studies should be performed after corrective and preventive actions to detect a possible decrease in rejecting samples. PMID:25351356

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

    SciTech Connect

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

    SciTech Connect

    Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao; Wu, William K.K.; Chan, Matthew T.V.; Zhang, Jie; Li, Haibin; Qin, Ke; Sun, Xuyong

    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.

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

    PubMed

    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

  15. Acute Liver Allograft Antibody-Mediated Rejection: an inter-institutional study of routine histopathological features

    PubMed Central

    O'Leary, Jacqueline G.; Shiller, S. Michelle; Bellamy, Christopher; Nalesnik, Michael A.; Kaneku, Hugo; Terasaki, Paul I.; Klintmalm, Göran B.; Demetris, Anthony J.

    2015-01-01

    Acute antibody-mediated rejection (AMR) occurs in a minority of sensitized liver transplant recipients. Although histopathologic characteristics have been described, a generalizable scoring system used to trigger a more in-depth analysis is needed to screen for this rare but important finding. Toward this goal, we created a training and validation cohort from 3 high volume liver transplant programs of putative acute AMR and control cases that were evaluated blindly by 4 independent transplant pathologists. The evaluations were performed on H&E sections alone without knowledge of serum DSA results nor C4d stains. Characteristics strongly correlated with acute AMR included portal eosinophilia (OR=4.37, p<0.001), portal vein endothelial cell hypertrophy (OR=2.88, p<0.001), and eosinophilic central venulitis (OR=2.48, p=0.003). These and other characteristics were incorporated into models created from the training cohort alone. The final Acute-AMR (aAMR) score exhibited a strong correlation with acute AMR in the training (OR=2.86, p<0.001) and validation cohort (OR=2.49, p<0.001). SPSS tree classification was used to select 2 cutoffs, one that optimized specificity at a score >1.75 (sensitivity = 34%, specificity = 87%) and a second that optimized sensitivity at a score >1.0 (sensitivity = 81%, specificity = 71%). In conclusion, routine histopathological features of the aAMR score can be used to screen for acute AMR on routine H&E in liver transplant biopsies, a diagnosis that requires substantiation by donor-specific HLA alloantibody testing, C4d staining, and exclusion of other insults. PMID:25045154

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

    PubMed Central

    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

    2016-01-01

    Abstract 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

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

    PubMed

    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

  18. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab

    PubMed Central

    Khan, Saif A.; Al-Riyami, Dawood; Al-Mula Abed, Yasser W.; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M.

    2016-01-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR. PMID:27606122

  19. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab.

    PubMed

    Khan, Saif A; Al-Riyami, Dawood; Al-Mula Abed, Yasser W; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M

    2016-08-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR. PMID:27606122

  20. Effect of graft preservation and acute rejection on hypoxia-inducible factor-1 in rat cardiac allografts.

    PubMed

    Keränen, M A I; Nykänen, A I; Krebs, R; Tuuminen, R; Sandelin, H; Koskinen, P K; Lemström, K B

    2006-12-01

    Hypoxia plays an integral part in cardiac transplantation as prolonged graft preservation is an individual risk factor for the development of cardiac allograft vasculopathy (CAV). In this study we characterized the role of hypoxia-inducible factor-1 (HIF-1) during prolonged graft preservation, ischemia-reperfusion (I/R), acute rejection, and chronic rejection. Heart transplantations were performed from Dark Agouti (DA) to Wister-Furth (allo) or DA to DA (syn) rats, without immunosuppression (acute rejection model, harvested at day 5) or with cyclosporine (chronic rejection model, harvested at day 60). To study the effect of preservation on HIF-1 regulation, normal DA hearts were subjected to different cold ischemia times with or without 45 minutes of additional warm ischemia. The role of I/R was studied by harvesting syngrafts at different time points after reperfusion. Real-time reverse-transcriptase polymerase chain reaction quantified total HIF-1 mRNA, while enzyme-linked immunosorbent assay and immunohistochemistry quantified and localized HIF-1 protein. Our results show that HIF-1 nuclear immunoreactivity is increased during graft preservation and I/R leads to loss of nuclear HIF-1 immunoreactivity. Acute rejection induced HIF-1 in mRNA level. Our findings thus indicated that HIF-1 is activated during transplantation and suggested that manipulation of the HIF-1 pathway might reveal new therapeutic options to manage CAV. PMID:17175275

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

    PubMed Central

    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

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

    PubMed

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

    PubMed Central

    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

  4. Motion artifact cancellation and outlier rejection for clip-type ppg-based heart rate sensor.

    PubMed

    Shimazaki, Takunori; Hara, Shinsuke; Okuhata, Hiroyuki; Nakamura, Hajime; Kawabata, Takashi

    2015-01-01

    Heart rate sensing can be used to not only understand exercise intensity but also detect life-critical condition during sports activities. To reduce stress during exercise and attach heart rate sensor easily, we developed a clip-type photoplethysmography (PPG)-based heart rate sensor. The sensor can be attached just by hanging it to the waist part of undershorts, and furthermore, it employs the motion artifact (MA) cancellation technique. However, due to its low contact pressure, sudden jumps and drops, which are called "outliers," are often observed in the sensed heart rate, so we also developed a simple outlier rejection technique. By an experiment using five male subjects (4 sets per subject), we confirmed the MA cancellation and outlier rejection capabilities. PMID:26736684

  5. Alloreactive T Cells to Identify Risk HLA Alleles for Retransplantation After Acute Accelerated Steroid-Resistant Rejection.

    PubMed

    Leyking, S; Wolf, M; Mihm, J; Schaefer, M; Bohle, R M; Fliser, D; Sester, M; Sester, U

    2015-10-01

    The risk of rejection by cellular alloreactivity to the transplant donor is not routinely assessed. Here we analyzed alloreactive T cells in kidney transplant recipients and report how their detection may have helped to prevent rejection of a second kidney graft in a patient with a history of acute accelerated steroid-resistant nonhumoral rejection. Alloreactive CD4 and CD8 T cells were quantified using a flow-cytometric mixed lymphocyte reaction assay based on interferon-γ induction. A group of 16 nonrejecting transplant recipients did not show any alloreactive T-cell immunity to their respective donors, whereas alloreactivity to third-party controls was detectable. In the patient with rejection, HLA-specific antibodies were not detectable before and shortly after rejection, but after transplantation the patient showed exceptionally high frequencies of alloreactive T cells against 2 of 11 HLA-typed controls (0.604% and 0.791% alloreactive CD4 T cells and 0.792% and 0.978% alloreactive CD8 T cells) who shared HLA alleles (HLA-A*24, -B*44, -C*02, -DQB1*5) with the kidney donor. These HLA alleles were subsequently excluded for allocation of a second graft. No alloreactive T cells were observed toward the second kidney donor, and this transplantation was performed successfully. Thus, shared HLA alleles between the donor and third-party controls may suggest that alloreactive T cells had contributed to rejection of the first graft. The rejecting patient highlights that determination of cellular alloreactivity before transplantation may be applied to identify unacceptable mismatches and to reduce the risk for acute cellular rejection episodes. PMID:26518945

  6. Simulation of biochemical reactions with time-dependent rates by the rejection-based algorithm

    SciTech Connect

    Thanh, Vo Hong; Priami, Corrado

    2015-08-07

    We address the problem of simulating biochemical reaction networks with time-dependent rates and propose a new algorithm based on our rejection-based stochastic simulation algorithm (RSSA) [Thanh et al., J. Chem. Phys. 141(13), 134116 (2014)]. The computation for selecting next reaction firings by our time-dependent RSSA (tRSSA) is computationally efficient. Furthermore, the generated trajectory is exact by exploiting the rejection-based mechanism. We benchmark tRSSA on different biological systems with varying forms of reaction rates to demonstrate its applicability and efficiency. We reveal that for nontrivial cases, the selection of reaction firings in existing algorithms introduces approximations because the integration of reaction rates is very computationally demanding and simplifying assumptions are introduced. The selection of the next reaction firing by our approach is easier while preserving the exactness.

  7. Association of IL-6 promoter and IFN-γ gene polymorphisms with acute rejection of liver transplantation.

    PubMed

    Karimi, Mohammad Hossein; Daneshmandi, Saeed; Pourfathollah, Ali Akbar; Geramizadeh, Bita; Malekhosseini, Seyed Ali; Nikeghbalian, Saman; Yaghobi, Ramin; Bolandparvaz, Shahram

    2011-10-01

    Liver transplantation is one of the most important therapies for end-stage liver diseases and is associated with major problems including infections and acute rejection. The outcome of transplantation can be determined by immune responses as a key role in response to the graft. Inflammatory and anti-inflammatory mediators especially cytokines influence the graft microenvironment. Th1 and Th2 immune responses in contrast to regulatory responses cause acute rejection or help graft survival. In this study, we evaluated the gene polymorphisms of IL-6 G-174C, TGF-β T + 869C, IL-4 C-590T, and IFN-γ T + 874A cytokines in liver transplant patients. ARMS-PCR method was used to characterize IL-6 G-174C, TGF-β T + 869C and IFN-γ T + 874A polymorphisms and PCR-RFLP using AvaII restriction enzyme was done for IL-4 C-590T characterization in 70 liver transplant patients. Acute rejection episodes were diagnosed according to standard criteria. The analysis of the results showed that IL-6-174 GG genotype ( P = 0.009, OR = 4.333, 95% CI = 1.043-18.000), IL-6-174G allele (P = 0.011, OR = 5.273, 95% CI = 1.454-19.127) was more frequent and IFN-γ +874 TT genotype was less frequent (P = 0.043, OR = 0.143, 95% CI = 0.0118-1.190) in acute rejection than in non-rejection patients. TGF-β T + 869C and IL-4 C-590T frequencies were not significantly different (P > 0.05). According to the results, it can be conclude that IL-6 G-174C and IFN-γ T + 874A gene polymorphisms have predictive values for acute rejection after liver transplantation. High producer genotype of IL-6 is a genetic risk factor and IFN-γ is a protective factor for acute rejection development. PMID:21132384

  8. Prediction of Renal Allograft Acute Rejection Using a Novel Non-Invasive Model Based on Acoustic Radiation Force Impulse.

    PubMed

    Yang, Cheng; Jin, Yunjie; Wu, Shengdi; Li, Long; Hu, Mushuang; Xu, Ming; Rong, Ruiming; Zhu, Tongyu; He, Wanyuan

    2016-09-01

    Point shear wave elastography based on acoustic radiation force impulse is a novel technology used to quantify tissue stiffness by measuring shear wave speed. A total of 115 kidney transplantation recipients were consecutively enrolled in this prospective study. The patients were subdivided into two groups using 1 mo post-transplantation as the cutoff time for determining the development of acute rejection (AR). Shear wave speed was significantly higher in the AR group than in the non-AR group. We created a model called SEV, comprising shear wave speed, estimated glomerular filtration rate and kidney volume change, that could successfully discriminate patients with or without AR. The area under the receiver operating characteristic curve of SEV was 0.89, which was higher than values for other variables; it was even better in patients within 1 mo post-transplantation (0.954), but was lower than the estimated glomerular filtration rate in patients after 1 mo post-transplantation. Therefore, the SEV model may predict AR after renal transplantation with a high degree of accuracy, and it may be more useful in the early post-operative stage after renal transplantation. PMID:27267289

  9. Exogenous Lipocalin 2 Ameliorates Acute Rejection in a Mouse Model of Renal Transplantation

    PubMed Central

    Ashraf, M. I.; Schwelberger, H. G.; Brendel, K. A.; Feurle, J.; Andrassy, J.; Kotsch, K.; Regele, H.; Pratschke, J.; Maier, H. T.

    2016-01-01

    Abstract Lipocalin 2 (Lcn2) is rapidly produced by damaged nephron epithelia and is one of the most promising new markers of renal injury, delayed graft function and acute allograft rejection (AR); however, the functional importance of Lcn2 in renal transplantation is largely unknown. To understand the role of Lcn2 in renal AR, kidneys from Balb/c mice were transplanted into C57Bl/6 mice and vice versa and analyzed for morphological and physiological outcomes of AR at posttransplantation days 3, 5, and 7. The allografts showed a steady increase in intensity of interstitial infiltration, tubulitis and periarterial aggregation of lymphocytes associated with a substantial elevation in serum levels of creatinine, urea and Lcn2. Perioperative administration of recombinant Lcn2:siderophore:Fe complex (rLcn2) to recipients resulted in functional and morphological amelioration of the allograft at day 7 almost as efficiently as daily immunosuppression with cyclosporine A (CsA). No significant differences were observed in various donor–recipient combinations (C57Bl/6 wild‐type and Lcn2−/−, Balb/c donors and recipients). Histochemical analyses of the allografts showed reduced cell death in recipients treated with rLcn2 or CsA. These results demonstrate that Lcn2 plays an important role in reducing the extent of kidney AR and indicate the therapeutic potential of Lcn2 in transplantation. PMID:26595644

  10. Higher Risk of Acute Cellular Rejection in Lung Transplant Recipients with Cystic Fibrosis.

    PubMed

    Calabrese, Fiorella; Lunardi, Francesca; Nannini, Nazarena; Balestro, Elisabetta; Loy, Monica; Marulli, Giuseppe; Calabrese, Francesca; Vuljan, Stefania Edith; Schiavon, Marco; Perissinotto, Egle; Rea, Federico

    2015-01-01

    BACKGROUND Acute cellular rejection (ACR) affects up to 40% of recipients within the first year after lung transplant (LTx). The aim of this study was to determine the frequency of ACR and associated major risk factors in cystic fibrosis (CF) recipients. Bronchiolitis obliterans syndrome (BOS) and 1-year/long-term survival were also evaluated. MATERIAL AND METHODS ACR was reviewed in 643 scheduled biopsies from 44 CF (Group 1) versus 89 other recipients (Group 2). We performed univariate/multivariate analyses of risk factors for ACR and BOS, and survival analysis. RESULTS Group 1 showed higher ACR frequency, especially for ACR ≥ A2. Multivariable generalized linear models considering both native lung disease and age showed that higher values of ACR index were significantly related to the pretransplant diagnosis of CF. BOS and long-term survival were not influenced by the increased incidence of ACR. Poorer long-term survival was observed in Group 2. CONCLUSIONS CF recipients have a higher ACR risk, which may be due to enhanced immune activation related to a genetic disorder, and younger age. PMID:26718747

  11. Age Differences in the Rejection of False Memories: The Effects of Giving Warning Instructions and Slowing the Presentation Rate

    ERIC Educational Resources Information Center

    Carneiro, Paula; Fernandez, Angel

    2010-01-01

    Two experiments were conducted to examine whether children of different ages differ in their ability to reject associative false memories with the Deese-Roediger-McDermott (DRM) paradigm. Two different types of manipulations that are thought to facilitate false memory rejection in adults--slowing the presentation rate and issuing explicit…

  12. A 3’-UTR Polymorphism in Soluble Epoxide Hydrolase Gene Is Associated with Acute Rejection in Renal Transplant Recipients

    PubMed Central

    Gervasini, Guillermo; García-Cerrada, Montserrat; Coto, Eliecer; Vergara, Esther; García-Pino, Guadalupe; Alvarado, Raul; Fernández-Cavada, Maria Jesús; Suárez-Álvarez, Beatriz; Barroso, Sergio; Doblaré, Emilio; Díaz-Corte, Carmen; López-Larrea, Carlos; Cubero, Juan Jose

    2015-01-01

    Background and Purpose Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites that play a protective role against damaging processes that may occur after re-oxygenation of the graft. We aimed to investigate whether the presence of functional polymorphisms in the gene encoding soluble epoxy hydrolase (EPHX2), which metabolizes EETs to less active compounds, may play a role in the outcome of renal transplantation. Methods In a group of 259 Caucasian renal transplant recipients and 183 deceased donors, we determined the presence of three common EPHX2 SNPs, namely rs41507953 (K55R), rs751141 (R287Q) and rs1042032 A/G. Associations with parameters of graft function and the incidence of acute rejection were retrospectively investigated throughout the first year after grafting by logistic regression adjusting for clinical and demographic variables. Results Carriers of the rs1042032 GG genotype displayed significantly lower estimated glomerular filtration rate (eGFR) (38.15 ± 15.57 vs. 45.99 ± 16.05; p = 0.04) and higher serum creatinine values (1.57 ± 0.58 vs. 1.30 ± 0.47 g/dL; p=0.02) one year after grafting, compared to patients carrying the wildtype A-allele. The same GG genotype was also associated to increased risk of acute rejection. Interestingly, this association was observed for the genotype of both recipients [OR =6.34 (1.35-29.90); p = 0.015] and donors [OR = 5.53 (1.10-27.80); p=0.042]. A statistical model including both genotypes along with other meaningful demographic and clinical variables resulted in an increased significance for the association with the recipients’ genotype [OR=8.28 (1.21-74.27); p=0.031]. Conclusions Our results suggest that genetic variability in the EETs-metabolizing gene, EPHX2, may have a significant impact on the outcome of deceased-donor renal transplantation. PMID:26230946

  13. Selected Factors Related to Selective Service Rejection and Rejection Rate in Delaware (1967): A Study of the Characteristics of Young Men Failing to Meet Mental Qualifications for Military Service.

    ERIC Educational Resources Information Center

    Price, Jay R.

    This study sought information about selective service rejection in Delaware, specifically rejectee characteristics, reasons for rejection, and the high rejection rate in Delaware. The basic design was a modified case study method in which a sample of individual records were examined. Differences between this sample and national samples were tested…

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

    PubMed

    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

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

    PubMed Central

    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

  16. Acceptance rate and reasons for rejection of manuscripts submitted to Veterinary Radiology & Ultrasound during 2012.

    PubMed

    Lamb, Christopher R; Mai, Wilfried

    2015-01-01

    Better understanding of the reasons why manuscripts are rejected, and recognition of the most frequent manuscript flaws identified by reviewers, should help submitting authors to avoid these pitfalls. Of 219 manuscripts submitted to Veterinary Radiology & Ultrasound in 2012, none (0%) was accepted without revision, four (2%) were withdrawn by the authors, 99 (45%) were accepted after revision, and 116 (53%) were rejected. All manuscripts for which minor revision was requested, and 73/86 (85%) manuscripts for which major revision was requested, were ultimately accepted. Acceptance rate was greater for retrospective studies and for manuscripts submitted from countries in which English was the primary language. The prevalences of flaws in manuscripts were poor writing (62%), deficiencies in data (60%), logical or methodological errors (28%), content not suitable for Veterinary Radiology & Ultrasound (26%), and lack of new or useful knowledge (25%). Likelihood of manuscript rejection was greater for lack of new or useful knowledge and content not suitable than for other manuscript flaws. The lower acceptance rate for manuscripts from countries in which English was not the primary language was associated with content not suitable and not poor writing. Submitting authors are encouraged to do more to recognize and address manuscript flaws before submission, for example by internal review. Specifically, submitting authors should express clearly the potential added value of their study in the introduction section of their manuscript, describe completely their methods and results, and consult the Editor-in-Chief if they are uncertain whether their subject matter would be suitable for the journal. PMID:24798652

  17. Spontaneous resolution of acute rejection and tolerance induction with IL-2 fusion protein in vascularized composite allotransplantation.

    PubMed

    Jindal, R; Unadkat, J; Zhang, W; Zhang, D; Ng, T W; Wang, Y; Jiang, J; Lakkis, F; Rubin, P; Lee, W P A; Gorantla, V S; Zheng, X X

    2015-05-01

    Vascularized composite allotransplantation (VCA) has emerged as a treatment option for treating nonlife-threatening conditions. Therefore, in order to make VCA a safe reconstruction option, there is a need to minimize immunosuppression, develop tolerance-inducing strategies and elucidate the mechanisms of VCA rejection and tolerance. In this study we explored the effects of hIL-2/Fc (a long-lasting human IL-2 fusion protein), in combination with antilymphocyte serum (ALS) and short-term cyclosporine A (CsA), on graft survival, regulatory T cell (Treg) proliferation and tolerance induction in a rat hind-limb transplant model. We demonstrate that hIL-2/Fc therapy tips the immune balance, increasing Treg proliferation and suppressing effector T cells, and permits VCA tolerance as demonstrated by long-term allograft survival and donor-antigen acceptance. Moreover, we observe two distinct types of acute rejection (AR), progressive and reversible, within hIL-2/Fc plus ALS and CsA treated recipients. Our study shows differential gene expression profiles of FoxP3 versus GzmB, Prf1 or interferon-γ in these two types of AR, with reversible rejection demonstrating higher Treg to Teff gene expression. This correlation of gene expression profile at the first clinical sign of AR with VCA outcomes can provide the basis for further inquiry into the mechanistic aspects of VCA rejection and future drug targets. PMID:25676865

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

    PubMed

    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

  19. Macrochimerism in intestinal transplantation: association with lower rejection rates and multivisceral transplants, without GVHD

    PubMed Central

    Zuber, Julien; Rosen, Sarah; Shonts, Brittany; Sprangers, Ben; Savage, Thomas M.; Richman, Sarah; Yang, Suxiao; Lau, Sai Ping; DeWolf, Susan; Farber, Donna; Vlad, George; Zorn, Emmanuel; Wong, Waichi; Emond, Jean; Levin, Bruce; Martinez, Mercedes; Kato, Tomoaki; Sykes, Megan

    2015-01-01

    Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft-vs-host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year post-transplant. Although only one iITx patient experienced GVHD, T-cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre-formed high titer donor-specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among non-sensitized patients, MVTx recipients exhibited greater T and B-cell chimerism than either iITx and iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients. PMID:25988811

  20. Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants, Without GVHD.

    PubMed

    Zuber, J; Rosen, S; Shonts, B; Sprangers, B; Savage, T M; Richman, S; Yang, S; Lau, S P; DeWolf, S; Farber, D; Vlad, G; Zorn, E; Wong, W; Emond, J; Levin, B; Martinez, M; Kato, T; Sykes, M

    2015-10-01

    Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft-vs-host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year posttransplant. Although only one iITx patient experienced GVHD, T cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre-formed high-titer donor-specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among nonsensitized patients, MVTx recipients exhibited greater T and B cell chimerism than either iITx or iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients. PMID:25988811

  1. ELISA-based detection of C4d after liver transplantation--a helpful tool for differential diagnosis between acute rejection and HCV-recurrence?

    PubMed

    Schmeding, Maximilian; Kienlein, Stefan; Röcken, Christoph; Neuhaus, Ruth; Neuhaus, Peter; Heidenhain, Christoph; Neumann, Ulf P

    2010-08-01

    Hepatitis-C is the most common indication for liver transplantation. Recurrence of HCV is universal leading to graft failure in up to 40% of all patients. The differentiation between acute rejection and recurrent hepatitis-C is crucial as rejection treatments are likely to aggravate HCV-recurrence. Histological examination of liver biopsy remains the gold standard for diagnosis of acute rejection but has failed in the past to distinguish between acute rejection and recurrent hepatitis-C. In a retrospective study we have recently reported that C4d as a marker of the activated complement cascade is detectable in a hepatic specimen in acute rejection after liver transplantation and may serve as a valuable tool in differential diagnosis between ACR and HCV-recurrence. We performed a prospective analysis by ELISA measurement of C4d concentration in cryo-preserved liver biopsies of LTX patients who had either experienced acute rejection, hepatitis-C recurrence or displayed no pathological alterations (controls). Opposed to our immunohistologically based findings in paraffinized tissue we were unable to detect significant differences of C4d concentration in ELISA of cryo-preserved liver tissue. Consequently the role and potential value of C4d as a diagnostic marker may not be determined using ELISA-based tissue evaluation. PMID:20558292

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

    PubMed Central

    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

  3. Clinical validation of an artificial neural network trained to identify acute allograft rejection in liver transplant recipients.

    PubMed

    Hughes, V F; Melvin, D G; Niranjan, M; Alexander, G A; Trull, A K

    2001-06-01

    Artificial neural networks (ANNs) are techniques of nonlinear data modeling that have been studied in a wide variety of medical applications. An ANN was developed to assist in the diagnosis of acute rejection in liver transplant recipients. We investigated the diagnostic accuracy of this ANN on a new data set of patients from the same hospital. In addition, we compared the diagnostic accuracy of the ANN with that of the individual input variables (alanine aminotransferase [ALT] and bilirubin levels and day posttransplantation). Clinical and biochemical data were collected retrospectively for 124 consecutive liver transplantations (117 patients) over the first 3 months after transplantation. Diagnostic accuracy was calculated using receiver operating characteristic (ROC) curve analysis. The ANN differentiated rejection from rejection-free episodes in the new data set over the first 3 months posttransplantation with an area under the ROC curve of 0.902 and sensitivity and specificity of 80.0% and 90.1% at the optimum decision threshold, respectively. The ANN was significantly more specific than ALT or bilirubin level or day posttransplantation at their corresponding optimum decision thresholds (P <.0001). Peak ANN output occurred 1 day earlier than peak values for either ALT or bilirubin (P <.005). The diagnostic accuracy of the ANN was greater than that of any of the individual variables that had been used as inputs. It would be a useful adjunct to conventional liver function tests for monitoring liver transplant recipients in the early postoperative period. PMID:11443576

  4. Diagnostic Performance of Echocardiography for the Detection of Acute Cardiac Allograft Rejection: A Systematic Review and Meta-Analysis

    PubMed Central

    Pan, Xudong; Sun, Lizhong

    2015-01-01

    Objective Many studies have addressed the diagnostic performance of echocardiography to evaluate acute cardiac allograft rejection compared with endomyocardial biopsy. But the existence of heterogeneity limited its clinical application. Thus, we conducted a comprehensive, systematic literature review and meta-analysis for the purpose. Methods Studies prior to September 1, 2014 identified by Medline/PubMed, EMBASE and Cochrance were examined by two independent reviews. We conducted meta-analysis by using Meta-DiSc 1.4 software. An assessment tool of QUADAS-2 was applied to evaluate the risk of bias and applicability of the studies. Results Thirty studies met the inclusion criteria of meta-analysis. The four parameters of pressure half time, isovolumic relaxation time, index of myocardial performance and late diastolic mitral annular motion velocity were included in the meta-analysis, with a pooled diagnostic odds ratio of 10.43, 6.89, 15.95 and 5.68 respectively, and the area under the summary receiver operating characteristic curves value of 0.829, 0.599, 0.871 and 0.685 respectively. Conclusion The meta-analysis and systematic review demonstrate that no single parameter of echocardiography showed a reliable diagnostic performance for acute cardiac allograft rejection. A result of echocardiography for ACAR should be comprehensively considered by physicians in the context of clinical presentations and imaging feature. PMID:25822627

  5. Gene Silencing of 4-1BB by RNA Interference Inhibits Acute Rejection in Rats with Liver Transplantation

    PubMed Central

    Shi, Yang; Hu, Shuqun; Song, Qingwei; Yu, Shengcai; Zhou, Xiaojun; Yin, Jun; Qin, Lei; Qian, Haixin

    2013-01-01

    The 4-1BB signal pathway plays a key role in organ transplantation tolerance. In this study, we have investigated the effect of gene silencing of 4-1BB by RNA interference (RNAi) on the acute rejection in rats with liver transplantation. The recombination vector of lentivirus that contains shRNA targeting the 4-1BB gene (LV-sh4-1BB) was constructed. The liver transplantation was performed using the two-cuff technique. Brown-Norway (BN) recipient rats were infected by the recombinant LVs. The results showed that gene silencing of 4-1BB by RNAi downregulated the 4-1BB gene expression of the splenic lymphocytes in vitro, and the splenic lymphocytes isolated from the rats with liver transplantation. LV-sh4-1BB decreased the plasma levels of liver injury markers including AST, ALT, and BIL and also decreased the level of plasma IL-2 and IFN-γ in recipient rats with liver transplantation. Lentivirus-mediated delivery of shRNA targeting 4-1BB gene prolonged the survival time of recipient and alleviated the injury of liver morphology in recipient rats with liver transplantation. In conclusion, our results demonstrate that gene silencing of 4-1BB by RNA interference inhibits the acute rejection in rats with liver transplantation. PMID:23484089

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

    PubMed

    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

  7. Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes.

    PubMed

    Modena, B D; Kurian, S M; Gaber, L W; Waalen, J; Su, A I; Gelbart, T; Mondala, T S; Head, S R; Papp, S; Heilman, R; Friedewald, J J; Flechner, S M; Marsh, C L; Sung, R S; Shidban, H; Chan, L; Abecassis, M M; Salomon, D R

    2016-07-01

    Interstitial fibrosis and tubular atrophy (IFTA) is found in approximately 25% of 1-year biopsies posttransplant. It is known that IFTA correlates with decreased graft survival when histological evidence of inflammation is present. Identifying the mechanistic etiology of IFTA is important to understanding why long-term graft survival has not changed as expected despite improved immunosuppression and dramatically reduced rates of clinical acute rejection (AR) (Services UDoHaH. http://www.ustransplant.org/annual_reports/current/509a_ki.htm). Gene expression profiles of 234 graft biopsy samples were obtained with matching clinical and outcome data. Eighty-one IFTA biopsies were divided into subphenotypes by degree of histological inflammation: IFTA with AR, IFTA with inflammation, and IFTA without inflammation. Samples with AR (n = 54) and normally functioning transplants (TX; n = 99) were used in comparisons. A novel analysis using gene coexpression networks revealed that all IFTA phenotypes were strongly enriched for dysregulated gene pathways and these were shared with the biopsy profiles of AR, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. These molecular biopsy profiles correlated with future graft loss in IFTA samples without inflammation. PMID:26990570

  8. Data-nonintrusive photonics-based credit card verifier with a low false rejection rate.

    PubMed

    Sumriddetchkajorn, Sarun; Intaravanne, Yuttana

    2010-02-10

    We propose and experimentally demonstrate a noninvasive credit card verifier with a low false rejection rate (FRR). Our key idea is based on the use of three broadband light sources in our data-nonintrusive photonics-based credit card verifier structure, where spectral components of the embossed hologram images are registered as red, green, and blue. In this case, nine distinguishable variables are generated for a feed-forward neural network (FFNN). In addition, we investigate the center of mass of the image histogram projected onto the x axis (I(color)), making our system more tolerant of the intensity fluctuation of the light source. We also reduce the unwanted signals on each hologram image by simply dividing the hologram image into three zones and then calculating their corresponding I(color) values for red, green, and blue bands. With our proposed concepts, we implement our field test prototype in which three broadband white light light-emitting diodes (LEDs), a two-dimensional digital color camera, and a four-layer FFNN are used. Based on 249 genuine credit cards and 258 counterfeit credit cards, we find that the average of differences in I(color) values between genuine and counterfeit credit cards is improved by 1.5 times and up to 13.7 times. In this case, we can effectively verify credit cards with a very low FRR of 0.79%. PMID:20154742

  9. Role of basiliximab in the prevention of acute cellular rejection in adult to adult living-related liver transplantation: a single center experience

    PubMed Central

    Gruttadauria, S; Mandalà, L; Biondo, D; Spampinato, M; Lamonaca, V; Volpes, R; Vizzini, G; Marsh, JW; Marcos, A; Gridelli, B

    2007-01-01

    We report our single center experience with the use of basiliximab, a chimeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor (CD25), in combination with a steroid- and tacrolimus-based regimen in adult to adult living-related liver transplantation (ALRLT). Sixty consecutive ALRLTs were analyzed. All patients received two 20-mg doses of basiliximab (days 0 and 4 after transplantation) followed by tacrolimus (0.15 mg/kg/day; 10–15 ng/mL target trough levels) and a dose regimen of steroids (starting with 20 mg iv, switched to po as soon as the patient was able to eat, and weaned off within 1–2 months). Follow-up ranged from 6 to 1699.4 days after transplantation (mean 517.5 days, SD ± 413.4; median 424 days). Of the recipients, 95% remained rejection-free during follow-up, with an actuarial rejection-free probability of 96.61% within 3 months. Three patients had episodes of biopsy-proven acute cellular rejection (ACR). Actuarial patient and graft survival rates at 3 years were 82.09% and 75.61%. Six patients (10%) experienced sepsis. There was no evidence of cytomegalovirus infections or side-effects related to the basiliximab. We found zero de novo malignancy, although we observed 5 patients with metastatic spread of their primary malignancy during the follow-up. Basiliximab in association with tacrolimus and steroids is effective in reducing episodes of ACR and increasing ACR-free survival after ALRLT. PMID:19707350

  10. Inclusive Teachers' Concern and Rejection toward Their Students: Investigating the Validity of Ratings and Comparing Student Groups

    ERIC Educational Resources Information Center

    Cook, Bryan G.; Cameron, David L.

    2010-01-01

    This article reports two related studies. In the first study, concern and rejection ratings of 14 inclusive teachers toward 26 students with disabilities were correlated with teacher--student interactions. Partial correlations, controlling for severity of disability, indicated that instructional-academic interactions corresponded significantly…

  11. Mating behaviour of Pseudodiaptomus annandalei (Copepoda Calanoida) with emphasis on rejection rate

    NASA Astrophysics Data System (ADS)

    Dur, G.; Souissi, S.; Schmitt, F. G.; Hwang, J. S.; Cheng, S. H.

    2009-04-01

    swimming trajectories are more convoluted, indicating that males explore larger volume of fluid to increase the probability to encounter a female. The mate finding behaviour appears to depend not only on chemical signal but also on hydromechanical signals. Some males exhibited shifts of direction when females were passing by. When male intercepted a chemical trail left by a female, they initiate tracking behaviour racing up the trail with increasing speed. Males pursued pheromone trails up to 24 sec old and 10 mm long. Most studies of mating behaviour have focused on detection and sometimes pursuit, but few have addressed the other components of successful mating, namely, capture and copulation. Moreover, mate choice issue has largely been ignored in regards to pelagic copepods. Consequently very few are known about the plasticity of rejection rates as a function of mate encounter rates. The second aim of this experiment is to describe the process used by female to select their mate and to fill the gap in the quantification of mating success. Once caught by a male, P. annandalei's females entered in intensive dance which sometimes lead to shake off the males suggesting a female mate choice. The three-dimensional trajectories described by the couple during this event were characterized by fast loops and intense jumps. Individual's access to mates may be affected by operational sex ratios, causing strong variation in mating success. We finally manipulated adult sex ratios of the brackish copepod P. annandalei, to examine the influence of population sex ratio on mating success of P. annandalei in a final set of experiment concluding the investigation. It should be notice that, to our knowledge, it the first quantification ever done before. The plasticity of rejection rate was therefore investigated as a function of sex-ratio and mate encounter rate. The encounter rate reached maximum value for balanced proportion of male and female and decreased as the sex ratio unbalanced

  12. CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection

    PubMed Central

    Harper, Simon J. F.; Ali, Jason M.; Wlodek, Elizabeth; Negus, Marg C.; Harper, Ines G.; Chhabra, Manu; Qureshi, M. Saeed; Mallik, Mekhola; Bolton, Eleanor; Bradley, J. Andrew; Pettigrew, Gavin J.

    2015-01-01

    Adaptive CD8 T-cell immunity is the principal arm of the cellular alloimmune response, but its development requires help. This can be provided by CD4 T cells that recognize alloantigen “indirectly,” as self-restricted allopeptide, but this process remains unexplained, because the target epitopes for CD4 and CD8 T-cell recognition are “unlinked” on different cells (recipient and donor antigen presenting cells (APCs), respectively). Here, we test the hypothesis that the presentation of intact and processed MHC class I alloantigen by recipient dendritic cells (DCs) (the “semidirect” pathway) allows linked help to be delivered by indirect-pathway CD4 T cells for generating destructive cytotoxic CD8 T-cell alloresponses. We show that CD8 T-cell–mediated rejection of murine heart allografts that lack hematopoietic APCs requires host secondary lymphoid tissue (SLT). SLT is necessary because within it, recipient dendritic cells can acquire MHC from graft parenchymal cells and simultaneously present it as intact protein to alloreactive CD8 T cells and as processed peptide alloantigen for recognition by indirect-pathway CD4 T cells. This enables delivery of essential help for generating cytotoxic CD8 T-cell responses that cause rapid allograft rejection. In demonstrating the functional relevance of the semidirect pathway to transplant rejection, our findings provide a solution to a long-standing conundrum as to why SLT is required for CD8 T-cell allorecognition of graft parenchymal cells and suggest a mechanism by which indirect-pathway CD4 T cells provide help for generating effector cytotoxic CD8 T-cell alloresponses at late time points after transplantation. PMID:26420874

  13. [The influence of selected cytokine gene polymorphisms on the occurrence of acute and chronic rejection and on kidney graft survival].

    PubMed

    Kocierz, Magdalena; Kujawa-Szewieczek, Agata; Kolonko, Aureliusz; Chudek, Jerzy; Wiecek, Andrzej

    2009-01-01

    Genetically determined interindividual differences in the production of mediators of immune response may influence the outcomes of kidney transplantation. Of the cytokine gene polymorphisms that determine the level of gene expression, TNF-a -08G/A, IFN-g +874T/A and microsatellite (CA)n, TGF-b1 +869T/C and +915G/C, IL-6 -174G/C, and IL-10 -592C/A, -819C/T, and -1082G/A seem to have the strongest impact on graft survival. Increased risk of acute rejection (AR) was demonstrated for high-producing genotypes of pro-inflammatory cytokines such as TNF-a and IFN-g, while the association with polymorphisms of TGF-b1 and IL-10 remains unclear. A high production of profibrotic TGF-b1 is associated with interstitial fibrosis and tubular atrophy (IF/TA). In contrast, high genetically determined IL-6 gene expression played a protective role in the development of chronic rejection (CR). The risk of graft loss was greater among high TNF-a and low TGF-b1 or IL-6 producers. The results of kidney transplantation are also influenced by the donor's cytokine expression profile. Low IL-6 production donor genotype was associated with a higher prevalence of AR, CR, and IF/TA. Low donor transcriptional TGF-b1 gene activity predisposed the recipient to AR episodes and high IFN-g expression to IF/TA development. To date, study results are highly inconsistent, so the applicability of cytokine polymorphism genotyping remains questionable. In summary, it is difficult to conclude whether or not cytokine polymorphism genotyping is useful in the risk assessment of rejection and kidney graft survival and in applying optimal immunosuppressive medication. PMID:20097948

  14. Characteristics of Circulating Donor-Specific Anti-HLA Antibodies and Acute Rejection in the Kidney Allograft

    PubMed Central

    Kannabhiran, Dinesh; Lee, John; Schwartz, Joseph E.; Friedlander, Rex; Aull, Meredith; Muthukumar, Thangamani; Campbell, Sean; Epstein, David; Seshan, Surya V.; Kapur, Sandip; Sharma, Vijay K.; Suthanthiran, Manikkam; Dadhania, Darshana

    2016-01-01

    Background Characteristics of pretransplant antibodies directed at donor HLA (DSA) associated with adverse outcomes in kidney transplant recipients are being elucidated but uncertainties exist. Methods Prospectively screening of pretransplant sera from 543 kidney recipients using single antigen bead assays identified 154 recipients with DSA and 389 without. We investigated the association of DSA features to acute rejection (AR) and graft failure. Results One-year AR incidence was higher in DSA positive group (P<0.001), primarily due to antibody mediated rejection (AMR, 13% vs. 1.8%, P<0.001) and not T-cell mediated rejection (ACR, 5% vs.6%, P=0.65). Risk of AMR increased progressively with a rise in DSA MFI-Sum (P<0.0001). Both DSA MFI-Sum ≥6000 (OR=18; 95%CI, 7.0 to 47; P<0.001) and DSA specificity, presence of DSA against both HLA class I and II (OR=39; 95%CI, 14 to 106; P<0.0001), predicted one-year AMR, independent of other covariates. In a combined model, DSA specificity predicted AMR, independent of DSA MFI-Sum. In multivariable Cox proportional hazards models, the covariate-adjusted hazard ratio for graft failure was 2.03 (95%CI, 1.05 to 3.92; P=0.04) for DSA MFI-Sum≥6000 and 2.23 (95% CI, 1.04 to 4.80; P=0.04) for class I and II DSA. Prediction of graft loss was not independent of AMR. Conclusions Our study supports the hypothesis that characterization of pretransplant DSA, specifically presence of DSA against both HLA class I and II and the strength, as quantified by DSA MFI-Sum, is useful to estimate AMR and graft failure risk in kidney graft recipients. Elevated risk of graft failure is attributable to increased risk of AMR. PMID:25629531

  15. Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts From Acute Rejection.

    PubMed

    Young, J S; Chen, J; Miller, M L; Vu, V; Tian, C; Moon, J J; Alegre, M-L; Sciammas, R; Chong, A S

    2016-08-01

    Antibody-mediated rejection has emerged as the leading cause of late graft loss in kidney transplant recipients, and inhibition of donor-specific antibody production should lead to improved transplant outcomes. The fusion protein cytotoxic T lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocks T cell activation and consequently inhibits T-dependent B cell antibody production, and the current paradigm is that CTLA4-Ig is effective with naïve T cells and less so with activated or memory T cells. In this study, we used a mouse model of allosensitization to investigate the efficacy of continuous CTLA4-Ig treatment, initiated 7 or 14 days after sensitization, for inhibiting ongoing allospecific B cell responses. Delayed treatment with CTLA4-Ig collapsed the allospecific germinal center B cell response and inhibited alloantibody production. Using adoptively transferred T cell receptor transgenic T cells and a novel approach to track endogenous graft-specific T cells, we demonstrate that delayed CTLA4-Ig minimally inhibited graft-specific CD4(+) and T follicular helper responses. Remarkably, delaying CTLA4-Ig until day 6 after transplantation in a fully mismatched heart transplant model inhibited alloantibody production and prevented acute rejection, whereas transferred hyperimmune sera reversed the effects of delayed CTLA4-Ig. Collectively, our studies revealed the unexpected efficacy of CTLA4-Ig for inhibiting ongoing B cell responses even when the graft-specific T cell response was robustly established. PMID:26928966

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    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

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

    PubMed Central

    Yamanaka, Kazuaki; Kakuta, Yoichi; Miyagawa, Shuji; Nakazawa, Shigeaki; Kato, Taigo; Abe, Toyofumi; Imamura, Ryoichi; Okumi, Masayoshi; Maeda, Akira; Okuyama, Hiroomi; Mizuno, Masashi; Nonomura, Norio

    2016-01-01

    Background The association of complement with the progression of acute T cell mediated rejection (ATCMR) is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs) in acute T-cell mediated rejection using rat and human renal allografts. Methods We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR) and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP) by immunohistochemical staining in human renal grafts and their clinical course. Results qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry), was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate. Conclusions We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR. PMID:26928779

  19. Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation

    PubMed Central

    Dedeoglu, Burç; Meijers, Ruud W. J.; Klepper, Mariska; Hesselink, Dennis A.; Baan, Carla C.; Litjens, Nicolle H. R.; Betjes, Michiel G. H.

    2016-01-01

    Background End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR). Methods 222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters. Results Of the 222 patients analyzed, 30 (14%) developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively) and the number of related donor kidney transplantation was significantly lower (p = 0.018) in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01) and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08). No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028). In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001). Conclusion Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR. PMID:26950734

  20. Inducible expression of indoleamine 2,3-dioxygenase attenuates acute rejection of tissue-engineered lung allografts in rats.

    PubMed

    Ebrahimi, Ammar; Kardar, Gholam Ali; Teimoori-Toolabi, Ladan; Toolabi, LadanTeimoori; Ghanbari, Hossein; Sadroddiny, Esmaeil

    2016-01-15

    Lung disease remains one of the principal causes of death worldwide and the incidence of pulmonary diseases is increasing. Complexity in treatments and shortage of donors leads us to develop new ways for lung disease treatment. One promising strategy is preparing engineered lung for transplantation. In this context, employing new immunosuppression strategies which suppresses immune system locally rather than systemic improves transplant survival. This tends to reduce the difficulties in transplant rejection and the systemic impact of the use of immunosuppressive drugs which causes side effects such as serious infections and malignancies. In our study examining the immunosuppressive effects of IDO expression, we produced rat lung tissues with the help of decellularized tissue, differentiating medium and rat mesenchymal stem cells. Transduction of these cells by IDO expressing lentiviruses provided inducible and local expression of this gene. To examine immunosuppressive properties of IDO expression by these tissues, we transplanted these allografts into rats and, subsequently, evaluated cytokine expression and histopathological properties. Expression of inflammatory cytokines IFNγ and TNFα were significantly downregulated in IDO expressing allograft. Moreover, acute rejection score of this experimental group was also lower comparing other two groups and mRNA levels of FOXP3, a regulatory T cell marker, upregulated in IDO expressing group. However, infiltrating lymphocyte counting did not show significant difference between groups. This study demonstrates that IDO gene transfer into engineered lung allograft tissues significantly attenuates acute allograft damage suggesting local therapy with IDO as a strategy to reduce the need for systemic immunosuppression and, thereby, its side effects. PMID:26506443

  1. Thallium kinetics in rat cardiac transplant rejection

    SciTech Connect

    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.

  2. Immune biomarker panel monitoring utilizing IDO enzyme activity and CD4 ATP levels: prediction of acute rejection versus viral replication events

    PubMed Central

    Dharnidharka, Vikas R.; Gupta, Sushil; Khasawneh, Eihab Al; Haafiz, Allah; Shuster, Jonathan J.; Theriaque, Douglas W.; Shahlaee, Amir H.; Garrett, Timothy J.

    2011-01-01

    Infections have become as important an event as acute rejection post-transplant for long-term allograft survival. Less invasive biomarkers tested so far predict risk for one event or the other, not both. We prospectively tested blood and urine monthly for twelve months post-transplant from children receiving a kidney transplant. The indoleamine 2,3 dioxygenase (IDO) enzyme pathway was assessed by mass spectrometry assays using the ratio of product L-kynurenine (kyn) to substrate tryptophan (trp). Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with acute rejection or major infection events or stable group (no events) in the next 30 days. The 25 subjects experienced 6 discrete episodes of acute rejection in 5 subjects and 16 discrete events of major infection in 14 subjects (7 BK viruria, 6 cytomegaloviremia, 1 Epstein-Barr and cytomegaloviremia, 2 transplant pyelonephritis). Mean serum kyn/trp ratios were significantly elevated in the group that experienced acute rejection (p = 0.02).Within-subject analyses revealed that over time, urine kyn/trp ratios showed an increase (p = 0.01) and blood CD4-ATP levels showed a decrease (p = 0.007) prior to a major infection event. These pilot results suggest that a panel of biomarkers together can predict over- or under-immunosuppression, but need independent validation. PMID:21492353

  3. Renal and Cardiac Endothelial Heterogeneity Impact Acute Vascular Rejection in Pig-to-Baboon Xenotransplantation

    PubMed Central

    Knosalla, C.; Yazawa, K.; Behdad, A.; Bodyak, N.; Shang, H.; Bühler, L.; Houser, S.; Gollackner, B.; Griesemer, A.; Schmitt-Knosalla, I.; Schuurman, H.-J.; Awwad, M.; Sachs, D. H.; Cooper, D. K. C.; Yamada, K.; Usheva, A.; Robson, S. C.

    2010-01-01

    Xenograft outcomes are dictated by xenoantigen expression, for example, Gal α 1, 3Gal (Gal), but might also depend on differing vascular responses. We investigated whether differential vascular gene expression in kidney and cardiac xenografts correlate with development of thrombotic microangiopathy (TM) and consumptive coagulation (CC). Immunosuppressed baboons underwent miniswine or hDAF pig kidney (n = 6) or heart (n = 7), or Gal-transferase gene-knockout (GalT-KO) (thymo)kidney transplantation (n = 14). Porcine cDNA miniarrays determined donor proinflammatory, apoptosis-related and vascular coagulant/fibrinolytic gene expression at defined time points; validated by mRNA, protein levels and immunopathology. hDAF-transgenic and GalT-KO xenografts, (particularly thymokidneys) exhibited prolonged survival. CC was seen with Gal-expressing porcine kidneys (3 of 6), only 1 of 7 baboons post-cardiac xenotransplantation and was infrequent following GalT-KO grafts (1 of 14). Protective-type genes (heme oxygenase-I, superoxide dismutases and CD39) together with von Willebrand factor and P-selectin were upregulated in all renal grafts. Transcriptional responses in Gal-expressing xenografts were comparable to those seen in the infrequent GalT-KO rejection. In cardiac xenografts, fibrin deposition was associated with increased plasminogen activator inhibitor-1 expression establishing that gene expression profiles in renal and cardiac xenografts differ in a quantitative manner. These findings suggest that therapeutic targets may differ for renal and cardiac xenotransplants. PMID:19422330

  4. Cyclosporine Does Not Prevent Microvascular Loss in Transplantation but Can Synergize With a Neutrophil Elastase Inhibitor, Elafin, to Maintain Graft Perfusion During Acute Rejection.

    PubMed

    Jiang, X; Nguyen, T T; Tian, W; Sung, Y K; Yuan, K; Qian, J; Rajadas, J; Sallenave, J-M; Nickel, N P; de Jesus Perez, V; Rabinovitch, M; Nicolls, M R

    2015-07-01

    The loss of a functional microvascular bed in rejecting solid organ transplants is correlated with fibrotic remodeling and chronic rejection; in lung allografts, this pathology is predicted by bronchoalveolar fluid neutrophilia which suggests a role for polymorphonuclear cells in microcirculatory injury. In a mouse orthotopic tracheal transplant model, cyclosporine, which primarily inhibits T cells, failed as a monotherapy for preventing microvessel rejection and graft ischemia. To target neutrophil action that may be contributing to vascular injury, we examined the effect of a neutrophil elastase inhibitor, elafin, on the microvascular health of transplant tissue. We showed that elafin monotherapy prolonged microvascular perfusion and enhanced tissue oxygenation while diminishing the infiltration of neutrophils and macrophages and decreasing tissue deposition of complement C3 and the membrane attack complex, C5b-9. Elafin was also found to promote angiogenesis through activation of the extracellular signal-regulated kinase (ERK) signaling pathway but was insufficient as a single agent to completely prevent tissue ischemia during acute rejection episodes. However, when combined with cyclosporine, elafin effectively preserved airway microvascular perfusion and oxygenation. The therapeutic strategy of targeting neutrophil elastase activity alongside standard immunosuppression during acute rejection episodes may be an effective approach for preventing the development of irreversible fibrotic remodeling. PMID:25727073

  5. Cyclosporine does not prevent microvascular loss in transplantation but can synergize with a neutrophil elastase inhibitor, elafin, to maintain graft perfusion during acute rejection

    PubMed Central

    Jiang, Xinguo; Nguyen, Tom T.; Tian, Wen; Sung, Yon K.; Yuan, Ke; Qian, Jin; Rajadas, Jayakumar; Sallenave, Jean-Michel; Nickel, Nils P.; de Jesus Perez, Vinicio; Rabinovitch, Marlene; Nicolls, Mark R.

    2015-01-01

    The loss of a functional microvascular bed in rejecting solid organ transplants is correlated with fibrotic remodeling and chronic rejection; in lung allografts, this pathology is predicted by bronchoalveolar fluid neutrophilia which suggests a role for polymorphonuclear cells in microcirculatory injury. In a mouse orthotopic tracheal transplant model, cyclosporine, which primarily inhibits T cells, failed as a monotherapy for preventing microvessel rejection and graft ischemia. To target neutrophil action that may be contributing to vascular injury, we examined the effect of a neutrophil elastase inhibitor, elafin, on the microvascular health of transplant tissue. We showed that elafin monotherapy prolonged microvascular perfusion and enhanced tissue oxygenation while diminishing the infiltration of neutrophils and macrophages and decreasing tissue deposition of complement C3 and the membrane attack complex, C5b-9. Elafin was also found to promote angiogenesis through activation of the extracellular signal-regulated kinase (ERK) signaling pathway but was insufficient as a single agent to completely prevent tissue ischemia during acute rejection episodes. However, when combined with cyclosporine, elafin effectively preserved airway microvascular perfusion and oxygenation. The therapeutic strategy of targeting neutrophil elastase activity alongside standard immunosuppression during acute rejection episodes may be an effective approach for preventing the development of irreversible fibrotic remodeling. PMID:25727073

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

    PubMed

    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

  7. Cellular and Functional Imaging of Cardiac Transplant Rejection

    PubMed Central

    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

  8. MicroRNA signature of intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.

    PubMed

    Asaoka, T; Sotolongo, B; Island, E R; Tryphonopoulos, P; Selvaggi, G; Moon, J; Tekin, A; Amador, A; Levi, D M; Garcia, J; Smith, L; Nishida, S; Weppler, D; Tzakis, A G; Ruiz, P

    2012-02-01

    Despite continuous improvement of immunosuppression, small bowel transplantation (SBT) is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need to uncover novel insights that will lead to strategies to achieve better control of ACR. We hypothesized that particular miRNAs provide critical regulation of the intragraft immune response. The aim of our study was to identify miRNAs involved in intestinal ACR. We examined 26 small intestinal mucosal biopsies (AR/NR group; 15/11) obtained from recipients after SBT or multivisceral transplantation. We investigated the expression of 384 mature human miRNAs and 280 mRNAs associated with immune, inflammation and apoptosis processes. We identified differentially expressed 28 miRNAs and 58 mRNAs that characterized intestinal ACR. We found a strong positive correlation between the intragraft expression levels of three miRNAs (miR-142-3p, miR-886-3p and miR-132) and 17 mRNAs including CTLA4 and GZMB. We visualized these miRNAs within cells expressing CD3 and CD14 proteins in explanted intestinal allografts with severe ACR. Our data suggested that miRNAs have a critical role in the activation of infiltrating cells during intestinal ACR. These differences in miRNA expression patterns can be used to identify novel biomarkers and therapeutic targets for immunosuppressive agents. PMID:22026534

  9. Modulation of lymphocyte subpopulations by extracorporeal photopheresis in patients with acute graft-versus-host disease or graft rejection.

    PubMed

    Lorenz, Katrin; Rommel, Katharina; Mani, Jiju; Jin, Nan; Hilgendorf, Inken; Ho, Anthony D; Freund, Mathias; Schmitt, Michael; Schmitt, Anita

    2015-03-01

    Extracorporeal photopheresis (ECP) constitutes a promising treatment for patients with steroid-refractory acute graft-versus-host disease (aGvHD) after allogeneic stem cell transplantation and for patients with graft rejection after solid organ transplantation (SOT). There is an increasing body of evidence that modulation of lymphocyte subsets might play a crucial role in the mechanism of action in ECP. We therefore analyzed immunological effects concomitantly with clinical findings in patients under ECP therapy using multicolor flow cytometry. In a patient with steroid-refractory aGvHD and a patient with progressive bronchiolitis obliterans syndrome (BOS) after double-lung transplantation, clinical responses to ECP therapy were paralleled by an increase of CD4 + CD25hiFoxP3 + regulatory T cells and a decrease of T(EMRA) (CD3 + CD8+ CD45RA+ CD62L+ effector memory T) cells as well as of natural killer (NK)T cells. In summary, immunomonitoring of T cell subsets can elucidate the mechanism of action in ECP. PMID:24913503

  10. Low incidence of acute rejection in hepatitis B virus positive liver transplant recipients and the impact of hepatitis B immunoglobulin.

    PubMed

    Veerappan, Annapoorani; VanWagner, Lisa B; Mathew, James M; Huang, Xuemei; Miller, Joshua; Lapin, Brittany; Levitsky, Josh

    2016-04-01

    Historically, hepatitis B virus (HBV) liver transplantation (LT) recipients have less acute cellular rejection (ACR) than those without HBV. We questioned whether this has persisted in an era of decreased Hepatitis B immunoglobulin use (HBIG) given its in vitro immunoregulatory effects. We compared the incidence, risk factors and outcomes of ACR among 40,593 primary LT recipients with HBV, hepatitis C, steatohepatitis, and immune liver disease (OPTN 2000-2011). We also assessed the in vitro effect of HBIG on alloimmune lymphoproliferation and regulatory T cell generation using mixed lymphocyte reactions. In multivariate analysis, HBV status remained a strong independent predictor of freedom from ACR (OR 0.58, 95% CI: 1.5-2.1). Patient (67.7% vs 72.3%) and graft (60.8% vs 69.1%) survival were significantly lower in patients with ACR versus no ACR for all causes except HBV. HBIG use had no statistical association with ACR. In vitro, HBIG at concentrations equivalent to clinical dosing did not inhibit lymphoproliferation or promote regulatory T cell development. In summary, the incidence and impact of ACR is lower now for HBV LT and does not appear to be secondary to HBIG by our in vitro and in vivo analyses. Rather, it may be due to the innate immunosuppressive properties of chronic HBV infection. PMID:26924082

  11. Impact of ABO Incompatibility on the Development of Acute Antibody-Mediated Rejection in Kidney Transplant Recipients Presensitized to HLA

    PubMed Central

    Chung, Byung Ha; Joo, Yu Young; Lee, Jaesin; Kim, Hyung Duk; Kim, Ji-Il; Moon, In Sung; Choi, Bum Soon; Oh, Eun-Jee; Park, Cheol Whee; Kim, Yong-Soo; Yang, Chul Woo

    2015-01-01

    Whether the coexistence of anti-A/B antibody and donor specific anti-HLA antibody (HLA-DSA) has a synergistic impact on the development of acute antibody-mediated rejection (AAMR) in kidney transplant recipients (KTRs) is unclear. This study includes 92 KTRs who received a kidney from an ABO-incompatible (ABOi) donor or were presensitized to donor HLA (HLAs) and 292 controls (CONT). HLAs was defined as a crossmatch positivity or the presence of HLA-DSA. We compared the incidence of AAMR among ABOi (n = 58), ABOi+HLAs (n = 12), HLAs (n = 22), and CONT (n = 292) groups and evaluated the risk factors and antibody type (anti-A/B vs. HLA-DSA) responsible for AAMR. AAMR developed less frequently in ABOi and CONT than in the ABOi+HLAs or HLAs (P < 0.05 for all); however, there was no difference between the ABOi+HLAs and HLAs groups. AAMR developed more frequently with strong HLA-DSA at baseline; however, high baseline anti-A/B titer did not affect AAMR development. Strong baseline HLA-DSA was an independent predictor for AAMR, however the baseline anti-A/B titer was not. All four AAMR episodes in ABOi+HLAs were positive to HLA-DSA but not to anti-A/B. In conclusion, ABO incompatibility does not increase the risk for AAMR in HLAs KTRs. PMID:25897756

  12. Corneal Allograft Rejection: Immunopathogenesis to Therapeutics

    PubMed Central

    Qazi, Yureeda; Hamrah, Pedram

    2014-01-01

    Corneal transplantation is among the most successful solid organ transplants. However, despite low rejection rates of grafts in the ‘low-risk’ setting, rejection can be as high as 70% when grafted into ‘high-risk’ recipient beds. Under normal homeostatic conditions, the avascular cornea provides a unique environment that facilitates immune and angiogenic privilege. An imbalance in pro-inflammatory, angiogenic and lymphangiogenic mediators leads to a breakdown in corneal immune privilege with a consequent host response against the donor graft. Recent developments in lamellar and endothelial keratoplasties have reduced the rates of graft rejection even more, while providing improved visual outcomes. The corneal layer against which an immune response is initiated, largely determines reversibility of the acute episode. While epithelial and stromal graft rejection may be treated with topical corticosteroids with higher success, acute endothelial rejection mandates a more aggressive approach to therapy due to the lack of regenerative capacity of this layer. However, current immunosuppressive regimens come with the caveat of ocular and systemic side effects, making prolonged aggressive treatment undesirable. With the advent of biologics, efficacious therapies with a superior side effect profile are on the horizon. In our review we discuss the mediators of ocular immune privilege, the roles of cellular and molecular immune players in graft rejection, with a focus on human leukocyte antigen and antigen presenting cells. Furthermore, we discuss the clinical risk factors for graft rejection and compare rates of rejection in lamellar and endothelial keratoplasties to traditional penetrating keratoplasty. Lastly, we present the current and upcoming measures of therapeutic strategies to manage and treat graft rejection, including an overview of biologics and small molecule therapy. PMID:24634796

  13. Elevated urinary sVCAM-1, IL6, sIL6R and TNFR1 concentrations indicate acute kidney transplant rejection in the first 2 weeks after transplantation.

    PubMed

    Reinhold, Stephan W; Straub, Rainer H; Krüger, Bernd; Kaess, Bernhard; Bergler, Tobias; Weingart, Christian; Banas, Miriam C; Krämer, Bernhard K; Banas, Bernhard

    2012-03-01

    We tested the hypothesis that increased urinary cytokine concentrations may indicate an acute kidney transplant rejection. Eight patients with an early rejection in their protocol biopsy about 14days after transplantation (group A), 9 patients with a biopsy proven rejection 2-3months after transplantation (group B) and 18 patients without acute rejection in their protocol biopsies both at 14days and 3months (group C, represents the control group) were chosen for this study. At the time of biopsy, the mean urinary concentration of interleukin 6 (IL6), soluble IL6 receptor (sIL6R), tumor necrosis factor receptor 1 (TNFR1), and soluble vascular cell adhesion molecule -1 (sVCAM-1) were significantly higher in patients with an early acute transplant rejection, i.e. in group A compared to patients in the control group (p<0.01). Additionally we found already 14days after transplantation significantly higher concentrations of urinary sIL6R and sVCAM-1 in group B patients who suffered of late acute rejection compared to patients with no acute rejection (group C, p<0.05). No significant correlation could be shown for interleukin 1 receptor antagonist (IL1ra), TNF, and TNFR2. In conclusion, elevated urinary concentrations of IL6, sIL6R, TNFR1 and sVCAM-1 clearly indicate an early acute transplant rejection. Especially sVCAM-1 may also serve as an early marker of an upcoming late rejection. However, further studies are warranted to verify the value of individual cytokine profiles to predict acute rejection episodes. PMID:22209080

  14. Acute antibody-mediated rejection in pediatric kidney transplants: a single center experience.

    PubMed

    Twombley, Katherine; Thach, Lonnie; Ribeiro, Annelise; Joseph, Catherine; Seikaly, Mouin

    2013-11-01

    aAMR is a potentially devastating complication of kidney transplantation. The incidence of aAMR in children, while thought to be rare, is not well defined, and there is a paucity of data on treatment regimens in children. We retrospectively reviewed the outcomes of our pediatric patients that were treated for aAMR between 2007 and 2009. Three adolescent Hispanic males were found to have aAMR. All three received deceased donor transplants, and all three verbalized non-adherence. Treatment consisted of rituximab, solumedrol, PE, and IVIgG in one patient, and PE, IVIgG, and bortezomib in two patients. The only side effect of therapy noted was mild hypotension with rituximab that resolved after decreasing the infusion rate. There were no reported infections two yr after treatment, and all of the viral monitoring in these patients remained negative. PMID:23901848

  15. High-rate partial nitrification treatment of reject water as a pretreatment for anaerobic ammonium oxidation (anammox).

    PubMed

    Zhang, Li; Yang, Jiachun; Hira, Daisuke; Fujii, Takao; Furukawa, Kenji

    2011-02-01

    In this study, a lab-scale swim-bed partial nitrification reactor was developed to treat ammonium-rich reject water to achieve an appropriate NO(2)(-)-N/NH(4)(+)-N mixture that could serve as a pretreatment for anaerobic ammonium oxidation (anammox). Strictly controlling the DO concentration was adopted as the main operational strategy. In addition, the influent concentrations of inorganic carbon/ammonium (IC/NH(4)(+)) and alkalinity/ammonium (Alk/NH(4)(+)) that were approximately 0.8 and 4.8, respectively, were regarded as the suitable ratios for the steady and high-rate operation of the reactor in this study. When reject water that was not diluted was introduced to this system, the maximum nitrogen loading rate was 5.9 kg-N/m(3)/day, the ammonium conversion rate was 3.1 kg-N/m(3)/day, and the effluent NO(2)-N/(NO(2)-N+NO(3)-N) percentage ratio was over 99.9%. Furthermore, DNA analysis confirmed the existence of AOB, which was responsible for the stable performance that was achieved in the PN reactor. PMID:21190840

  16. Non-invasive Diagnosis of Acute Cellular Rejection in Liver Transplant Recipients: A Proteomic Signature Validated by ELISA

    PubMed Central

    Massoud, Omar; Heimbach, Julie; Viker, Kimberly; Krishnan, Anuradha; Poterucha, John; Sanchez, William; Watt, Kymberly; Wiesner, Russell; Charlton, Michael

    2011-01-01

    Diagnosis of acute cellular rejection (ACR) requires a liver biopsy with attendant expense, and risk. The first aim was to prospectively determine, in an exploratory analysis, whether there is a serum proteome signature associated with histologically confirmed ACR. The second aim was to use simpler and faster ELISA-based assays for proteins identified as differentially abundant in the proteomic analysis to identify patients with ACR in a separate validation cohort. We used sequential high abundance protein depletion and iTRAQ LC/MS/MS mass spectrometry to characterize the serum proteome in serum samples of patients with ACR and without ACR. Of the 41 proteins identified as differentially abundant, 7 (serum amyloid A (SAA), complement 4 (C4), fibrinogen, complement 1q (C1q), complement 3 (C3), Heat Shock Protein 60 (HSP60), and Heat Shock Protein 70 (HSP70)) could be measured using ELISA-based assays in a validation cohort of patients with ACR (n=25) and without ACR (n=21). Mean ALT levels in patients with and without ACR were (mean +/− SD) 198+/−27 and 153+/−34 U/L respectively. Among the seven proteins for which ELISA assays were available, C4 and C1q were both independent predictors for ACR. C4 had the greatest predictivity in differentiating patients with/without ACR. C4 of ≤0.31gm/L had a 97% sensitivity, 62% specificity, 74% positive predictive value and 94% negative predictive value. The combination C4 ≤0.31 gm/L and ALT ≥70 IU/ml had 96% sensitivity, 81% specificity, 86% positive predictive value and 94% negative predictive value. In summary, in this exploratory analysis, serum complement C4 and ALT levels are highly predictive of ACR in liver transplant recipients. Confirmation in a prospective, larger, diverse population is needed. PMID:21618694

  17. Study of the association between the donors and recipients angiotensin-converting enzyme insertion/deletion gene polymorphism and the acute renal allograft rejection

    PubMed Central

    Azmandian, Jalal; Mohamadifar, Mohamadamir; Rahmanian-Koshkaki, Sara; Mehdipoor, Mohammad; Nematollahi, Mohamad-Hadi; Saburi, Amin; Mandegary, Ali

    2015-01-01

    Background: Angiotensin converting enzyme (ACE) is involved in various pathophysiological conditions including renal function. ACE levels are under genetic control. Objectives: This study was designed to investigate the association between the donors and recipients ACE-I/D gene polymorphism and risk of acute rejection outcome in renal allograft recipients. Patients and Methods: ACE-I/D polymorphism was determined in 200 donor-recipient pairs who had been referred to Afzalipour hospital in Kerman. ACE-I/D polymorphism was detected using polymerase chain reaction (PCR). Acute rejection (AR) during at least six months post-transplantation was defined as a 20% increase in creatinine level from the postoperative baseline in the absence of other causes of graft dysfunction which responded to antirejection therapy. Results: The observed allele frequencies were II 9.8%, ID 35.6% and DD 44.4% in donors and II 9.8%, ID 35.1% and DD 52.7% in recipients. There were no significant association between ACE genotypes and AR episodes (ORID=0.96 [0.18-5.00] and ORDD: 1.24 [0.25-6.07] for the donors) and (ORID: 0.29 [0.06-1.45] and ORDD: 0.75 [0.19-2.90] for the recipients). Conclusions: It seems that donor and recipient ACE-I/D genotype might not be a risk factor for acute renal allograft rejection. However, due to conflicting results from this and other studies, multicenter collaborative studies with more participants and concomitant evaluation of ACE polymorphism with other polymorphisms in renin–angiotensin system (RAS) are suggested to determine whether ACE genotypes are significant predictors of renal allograft rejection. PMID:26311652

  18. Effect of diabetes and acute rejection on liver transplant outcomes: An analysis of the organ procurement and transplantation network/united network for organ sharing database.

    PubMed

    Kuo, Hung-Tien; Lum, Erik; Martin, Paul; Bunnapradist, Suphamai

    2016-06-01

    The effects of diabetic status and acute rejection (AR) on liver transplant outcomes are largely unknown. We studied 13,736 liver recipients from the United Network for Organ Sharing/Organ Procurement Transplant Network database who underwent transplantation between 2004 and 2007 with a functioning graft for greater than 1 year. The association of pretransplant diabetes mellitus (PDM), new-onset diabetes after transplant (NODAT), and AR rates on allograft failure, all-cause mortality, and cardiovascular mortality were determined. To determine the differential and joint effects of diabetic status and AR on transplant outcomes, recipients were further stratified into 6 groups: neither (reference, n = 6600); NODAT alone (n = 2054); PDM alone (n = 2414); AR alone (n = 1448); NODAT and AR (n = 707); and PDM and AR (n = 513). An analysis with hepatitis C virus (HCV) serostatus was also performed (HCV recipients, n = 6384; and non-HCV recipient, n = 5934). The median follow-up was 2537 days. The prevalence of PDM was 21.3%. At 1 year after transplant, the rates of NODAT and AR were 25.5% and 19.4%, respectively. Overall, PDM, NODAT, and AR were associated with increased risks for graft failure (PDM, hazard ratio [HR] = 1.31, P < 0.01; NODAT, HR = 1.11, P = 0.02; AR, HR = 1.28, P < 0.01). A multivariate Cox regression analysis of the 6 recipient groups demonstrated that NODAT alone was not significantly associated with any study outcomes. The presence of PDM, AR, NODAT and AR, and PDM and AR were associated with higher overall graft failure risk and mortality risk. The presence of PDM was associated with higher cardiovascular mortality risk. The analyses in both HCV-positive and HCV-negative cohorts showed a similar trend as in the overall cohort. In conclusion, PDM and AR, but not NODAT, is associated with increased mortality and liver allograft failure. Liver Transplantation 22 796-804 2016 AASLD. PMID:26850091

  19. Smooth muscle cells of the coronary arterial tunica media express tumor necrosis factor-alpha and proliferate during acute rejection of rabbit cardiac allografts.

    PubMed Central

    Tanaka, H.; Swanson, S. J.; Sukhova, G.; Schoen, F. J.; Libby, P.

    1995-01-01

    Graft coronary arteriosclerosis (GCA) frequently limits the long-term success of cardiac transplantation. The pathogenic mechanisms of and stimuli that provoke GCA remain uncertain. Whatever the initiating factors, deranged control of smooth muscle cells (SMC) proliferation likely contributes to the intimal hyperplasia that produces obstructive lesions. To identify mediators that may contribute to ongoing modulation of SMC functions during acute rejection and to explore the mechanisms of the pathogenesis of graft coronary arteriosclerosis, we studied the kinetics of proliferation and the expression of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory and SMC growth-promoting cytokine, in coronary arterial SMCs in rabbit hearts transplanted heterotopically without immunosuppression. Hearts were harvested at 2 (n = 5), 5 (n = 5), and 8.2 +/- 0.4 (mean +/- SD, n = 5) days after transplantation, just before graft failure as judged clinically. SMC proliferation was assessed by continuous bromodeoxyuridine labeling (BrdU 10 mg/kg/d. s.q.). Whole heart cross sections were stained immunohistochemically with monoclonal antibodies that recognize TNF-alpha, BrdU, and SMCs (muscle alpha-actin). Major epicardial coronary arteries (five to nine profiles in each animal) were evaluated. Histological rejection grades by the International Society for Heart and Lung Transplantation scale at 2, 5, and 10 days were 1.6 +/- 0.9, 2.8 +/- 1.1, and 4.0 +/- 0.0, respectively. Medial SMCs in normal hearts and 2 days after transplant expressed little or no TNF-alpha and displayed negligible BrdU incorporation. At 5 days after transplantation, some medial SMCs stained for TNF-alpha and had a low BrdU labeling index (0.5 +/- 0.8%). At 8.2 days after transplant, almost all medial SMCs expressed TNF-alpha intensely and had a high labeling index (29.8 +/- 8.0%). These results demonstrate that acute rejection activates medial SMCs in coronary arteries to express TNF-alpha and that SMC

  20. 15 CFR 700.13 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... fill all the rated orders of equal priority status received on the same day, the person must accept... person shall not accept a rated order for delivery on a specific date if unable to fill the order by that date. However, the person must inform the customer of the earliest date on which delivery can be...

  1. 15 CFR 700.13 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... fill all the rated orders of equal priority status received on the same day, the person must accept... person shall not accept a rated order for delivery on a specific date if unable to fill the order by that date. However, the person must inform the customer of the earliest date on which delivery can be...

  2. 15 CFR 700.13 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... fill all the rated orders of equal priority status received on the same day, the person must accept... person shall not accept a rated order for delivery on a specific date if unable to fill the order by that date. However, the person must inform the customer of the earliest date on which delivery can be...

  3. 10 CFR 217.33 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... fill all of the rated orders of equal priority status received on the same day, the person must accept... not accept a rated order for delivery on a specific date if unable to fill the order by that date. However, the person must inform the customer of the earliest date on which delivery can be made and...

  4. 10 CFR 217.33 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... fill all of the rated orders of equal priority status received on the same day, the person must accept... not accept a rated order for delivery on a specific date if unable to fill the order by that date. However, the person must inform the customer of the earliest date on which delivery can be made and...

  5. 49 CFR 33.33 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... received on the same day, the person must accept, based upon the earliest delivery dates, only those orders... forms of civil transportation: (1) A person shall not accept a rated order for delivery on a specific... earliest date on which delivery can be made and offer to accept the order on the basis of that...

  6. 49 CFR 33.33 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... received on the same day, the person must accept, based upon the earliest delivery dates, only those orders... forms of civil transportation: (1) A person shall not accept a rated order for delivery on a specific... earliest date on which delivery can be made and offer to accept the order on the basis of that...

  7. 49 CFR 33.33 - Acceptance and rejection of rated orders.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... received on the same day, the person must accept, based upon the earliest delivery dates, only those orders... forms of civil transportation: (1) A person shall not accept a rated order for delivery on a specific... earliest date on which delivery can be made and offer to accept the order on the basis of that...

  8. Normalizing Rejection.

    PubMed

    Conn, Vicki S; Zerwic, Julie; Jefferson, Urmeka; Anderson, Cindy M; Killion, Cheryl M; Smith, Carol E; Cohen, Marlene Z; Fahrenwald, Nancy L; Herrick, Linda; Topp, Robert; Benefield, Lazelle E; Loya, Julio

    2016-02-01

    Getting turned down for grant funding or having a manuscript rejected is an uncomfortable but not unusual occurrence during the course of a nurse researcher's professional life. Rejection can evoke an emotional response akin to the grieving process that can slow or even undermine productivity. Only by "normalizing" rejection, that is, by accepting it as an integral part of the scientific process, can researchers more quickly overcome negative emotions and instead use rejection to refine and advance their scientific programs. This article provides practical advice for coming to emotional terms with rejection and delineates methods for working constructively to address reviewer comments. PMID:26041785

  9. Monitoring Pharmacologically Induced Immunosuppression by Immune Repertoire Sequencing to Detect Acute Allograft Rejection in Heart Transplant Patients: A Proof-of-Concept Diagnostic Accuracy Study

    PubMed Central

    Valantine, Hannah A.; Penland, Lolita; Luikart, Helen; Strehl, Calvin; Cohen, Garrett; Khush, Kiran K.; Quake, Stephen R.

    2015-01-01

    Background It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation. Methods and Findings In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412) that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without). We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient’s net state of immunosuppression (correlation with tacrolimus level, r = −0.867, 95% CI −0.968 to −0.523, p = 0.0014), as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9%) and a specificity of 82.0% (95% CI 72.1% to 89.1%) (cell-free donor-derived DNA as noninvasive gold standard). To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several

  10. Busulfan depletes neutrophils and delays accelerated acute rejection of discordant xenografts in the guinea pig-to-rat model.

    PubMed

    Brauer, Robert B; Beck, Tino; Stehle, Ingo; Kremer, Marcus; Heidecke, Claus-Dieter

    2003-01-01

    Complement factor C6 plays a critical role in mediating hyperacute rejection of discordant xenografts. In order to explore the mechanism of discordant xenograft rejection, we investigated kinetics and phenotypes of the cellular infiltrate in xenografts in untreated and leukocyte-depleted recipients, in relation to graft survival. Guinea pig cardiac xenografts were heterotopically transplanted to totally C6-deficient PVG (C-) rats. Grafts were removed after 0, 6, 12, and 24 h ( n = 6). Histological evaluation was performed with hematoxylin and eosin (H & E) and immunoperoxidase staining. The agents fucoidin and busulfan were applied to delay xenograft rejection further. Within 6 h, minimal perivascular edema with isolated infiltrating CD11b/c- and ED1-positive cells were found. An intense infiltration of CD11b/c- and ED1-positive cells with interstitial hemorrhage was present after 24 h, though with little CD161 and CD3 cell infiltration. Inhibition of cell adhesion by fucoidin did not prolong xenograft survival (34 +/- 15 h, n = 4, P<0.47), but the depletion of granulocytes by injection of busulfan did prolong survival of the discordant xenografts, to 62 +/- 22 h ( n = 7, P < or = 0.0039). These results demonstrate a significant effect of specific depletion of granulocytes and macrophages by busulfan therapy on guinea pig cardiac xenograft survival in PVG (C-) rats, suggesting the participation of these infiltrating cells in the xenoreactive rejection process. PMID:12545340

  11. β-cell-targeted blockage of PD1 and CTLA4 pathways prevents development of autoimmune diabetes and acute allogeneic islets rejection

    PubMed Central

    El Khatib, Moustafa; Sakuma, Toshie; Tonne, Jason M.; Mohamed, Magid S.; Holditch, Sara J.; Lu, Brian; Kudva, Yogish C.; Ikeda, Yasuhiro

    2015-01-01

    Protection of beta cells from autoimmune destruction potentially cures type 1 diabetes mellitus (T1D). During antigen presentation, interactions between cytotoxic T-lymphocyte antigen-4 (CTLA4) and B7 molecules, or programmed death 1 (PD1) and its ligand PDL1, negatively regulate immune responses in a non-redundant manner. Here, we employed beta cell-targeted adeno-associated virus serotype 8 (AAV8)-based vectors to over-express an artificial PDL1-CTLA4Ig polyprotein or IL10. Beta cell-targeted expression of PDL1-CTLA4Ig or IL10 preserved beta cell mass and protected NOD mice from T1D development. When NOD mice were treated with vectors at early onset of hyperglycemia, PDL1-CTLA4Ig or IL10 alone failed to normalize the early onset of hyperglycemia. When drug-induced diabetic mice received MHC-matched allo-islets, with or without pretreatment of the PDL1-CTLA4Ig-expressing vector, PDL1-CTLA4Ig-expressing islets were protected from rejection for at least 120 days. Similarly, transplantation of PDL1-CTLA4Ig-expressing MHC-matched islets into mice with established T1D resulted in protection of allo-islets from acute rejection, although islet grafts were eventually rejected. Thus, the present study demonstrates the potent immuno-suppressive effects of beta cell-targeted PDL1-CTLA4Ig overexpression against T1D development and allo-islet rejection. The gene-based simultaneous inhibition of PD1 and CTLA4 pathways provides a unique strategy for immunosuppression-free tissue/organ transplantation, especially in the setting of no established autoimmunity. PMID:25786871

  12. Association between the presence of anti-HLA antibodies with acute rejection and chronic allograft nephropathy in the first year after kidney transplantation.

    PubMed

    Toresan, R; Manfro, R C; Proença, M C C; Veronese, F J V; Salim, P H; da Silva, D M; Ribeiro, A R; Edelweiss, M I A; Pegas, K L; Jobim, L F J

    2008-04-01

    The clinical relevance of anti-HLA antibodies following kidney transplantation has been a recent focus of research. Patients who present anti-HLA antibodies in the posttransplantation period have shown higher incidences of acute rejection episodes (ARE) and chronic allograft nephropathy (CAN). The objective of this study was to evaluate the presence of anti-HLA antibodies during the first year after kidney transplantation and their association with the occurrence of ARE and CAN. Eighty-eight kidney transplant recipients were evaluated for the presence of IgG anti-HLA antibodies using an enzyme-linked immunosorbent assay (LAT-M and LAT-1240, One Lambda Inc, Calif, United States). Protocol kidney biopsies were performed in consenting patients. ARE and CAN were diagnosed by clinical, laboratory, and histopathological criteria. Anti-HLA antibodies were observed in 20 (22.7%) patients. At 1 year follow-up, 26.1% presented ARE and 51.2% developed CAN. Nine patients (45%) with antibodies developed ARE as opposed to 20.6% without antibodies and 64.7% developed CAN as opposed to 47.8% of those without antibodies. In the histological analysis, the anti-HLA antibodies were associated with Banff IIA ARE (P = .001) and Banff grade II CAN (P = .012). Routine posttransplantation search for antibodies may identify cases at higher risk for acute and chronic rejection, and perhaps help to tailor the immunosuppressive regimen. PMID:18454996

  13. Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients

    PubMed Central

    Djamali, Arjang; Muth, Brenda; Ellis, Thomas M.; Mohamed, Maha; Fernandez, Luis; Miller, Karen; Bellingham, Janet; Odorico, Jon; Mezrich, Joshua; Pirsch, John; D’Alessandro, Tony; Vidyasagar, Vijay; Hofmann, R. Michael; Torrealba, Jose; Kaufman, Dixon; Foley, David

    2013-01-01

    In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean calculated panel reactive antibody and MFImax ranged from 10.3% to 57.2%, and 262 to 1691, respectively, between low and high-risk protocols. Mean MFImax increased significantly from transplant to one-week and one-year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32% including 14% cellular, 12% antibody-mediated and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71 to 6.45) and increased donor specific antibodies at 1 week post-transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients. PMID:23447068

  14. Pre-Transplant Donor-Specific T-Cell Alloreactivity Is Strongly Associated with Early Acute Cellular Rejection in Kidney Transplant Recipients Not Receiving T-Cell Depleting Induction Therapy

    PubMed Central

    Crespo, Elena; Lucia, Marc; Cruzado, Josep M.; Luque, Sergio; Melilli, Edoardo; Manonelles, Anna; Lloberas, Nuria; Torras, Joan; Grinyó, Josep M.; Bestard, Oriol

    2015-01-01

    Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90), to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67). We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction therapy. PMID:25689405

  15. Immuno-histological assessment of sub-clinical acute and borderline rejection in renal allograft recipients: Data from a transplant center in India.

    PubMed

    Badwal, Sonia; Kumar, Arun; Hooda, A K; Varma, P P

    2015-11-01

    This single-center study was carried out on living related and unrelated renal transplant recipients (RTRs) to evaluate the usefulness of surveillance biopsies in monitoring stable renal allografts using immuno-histological markers for immune-activation. This is a prospective, longitudinal study. Protocol biopsies of 60 RTRs with stable graft function were evaluated at three, six and 12 months post-transplant. Immuno-histological evaluation was carried out using immune-activation markers (perforins, granzyme and interleukin-2R), phenotypic markers (CD-3 and CD-20), viral markers and C4d. The demographic and clinical profile was recorded for each patient. All cases of acute sub-clinical rejection (SCR) were treated and borderline SCR cases were followed-up without treatment. SCR at three and six months post-transplant was evident in 16.7% and 3.7% of RTRs, respectively. Positive statistical association of SCR was seen with HLA-DR mismatches, whereas patients receiving induction therapy and tacrolimus-based immunosuppression exhibited a lower incidence of SCR. T cell phenotype with persistent expression of immune-activation markers exhibited positive statistical association with interstitial fibrosis and tubular atrophy at 12-month follow-up biopsy. The mean creatinine levels were significantly lower in the protocol biopsy group than the non-protocol biopsy group. No significant difference was found between the mean creatinine levels of the SCR group after treatment and the non-SCR cases within the protocol biopsy group. Early treatment of sub-clinical acute rejection leads to better functional outcomes. However, persistent immune-activation is associated with chronicity and may have implications on long-term graft survival. PMID:26586064

  16. The kSORT Assay to Detect Renal Transplant Patients at High Risk for Acute Rejection: Results of the Multicenter AART Study

    PubMed Central

    Hsieh, Sue; Dai, Hong; Bestard, Oriol; Metes, Diana; Zeevi, Andrea; Gritsch, Albin; Cheeseman, Jennifer; Macedo, Camila; Peddy, Ram; Medeiros, Mara; Vincenti, Flavio; Asher, Nancy; Salvatierra, Oscar; Shapiro, Ron; Kirk, Allan; Reed, Elaine; Sarwal, Minnie M.

    2014-01-01

    Background Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR) increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR. Methods and Findings We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART) study. Gene expression was assessed by quantitative real-time PCR (QPCR) in one center. A 17-gene set—the Kidney Solid Organ Response Test (kSORT)—was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91–0.98), validated in 124 independent samples (AUC = 0.95; 95% CI 0.88–1.0) and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy). A novel reference-based algorithm (using 13 12-gene models) was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86–0.99). Further validation of kSORT is planned in prospective clinical observational and interventional trials. Conclusions The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary PMID

  17. Early Acute Antibody-Mediated Rejection of a Negative Flow Crossmatch 3rd Kidney Transplant with Exclusive Disparity at HLA-DP

    PubMed Central

    Mierzejewska, Beata; Schroder, Paul M.; Baum, Caitlin E.; Blair, Annette; Smith, Connie; Duquesnoy, Rene J.; Marrari, Marilyn; Gohara, Amira; Malhotra, Deepak; Kaw, Dinkar; Liwski, Robert; Rees, Michael A.; Stepkowski, Stanislaw

    2014-01-01

    Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA. PMID:24755353

  18. Validation of Single Nucleotide Polymorphisms (SNPs) Associated with Acute Rejection in Kidney Transplant Recipients Using a Large Multi-Center Cohort

    PubMed Central

    Oetting, William S.; Schladt, David P.; Leduc, Robert E.; Jacobson, Pamala A.; Guan, Weihua; Matas, Arthur J.; Israni, Ajay

    2011-01-01

    There have been numerous reports proposing a statistically significant association between a genetic variant, usually in the form of a single nucleotide polymorphism (SNP), and acute rejection (AR). Unfortunately, there are additional publications reporting a lack of association with AR when a different cohort of recipients was analyzed for the same SNP. The objective of this report was to attempt replication of these published finding in our own kidney allograft recipient cohort. We analyzed 23 genetic variants, previously reported to have a significant association with AR, using a cohort of 969 clinically well defined kidney transplant recipients. Only one SNP, rs6025 (Leiden mutation), within the coagulation factor V gene, showed a significant association with a p-value of 0.011 in a race adjusted analysis and 0.0003 in multiple variable analysis. An additional SNP, rs11706052 in IMPDH2, gave a modest p-value of 0.044 using multiple variable analysis which is not significant when multiple testing is taken into consideration. Our results suggest that careful validation of previously reported associations with AR is necessary and different strategies other than candidate gene studies can help to identify causative genetic variants associated with AR. PMID:21955043

  19. A pilot study of reduced dose cyclosporine and corticosteroids to reduce new onset diabetes mellitus and acute rejection in kidney transplant recipients

    PubMed Central

    2013-01-01

    Background New onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure after kidney transplantation. Methods In this multi-center, open label, single-arm pilot study, 49 adult (≥18 years of age), low immunologic risk, non-diabetic recipients of a first deceased or living donor kidney transplant received early steroid reduction to 5 mg/day combined with Thymoglobulin® (Genzyme Transplant, Cambridge, MA, USA) induction, low dose cyclosporine (2-hour post-dose (C2) target of 600 to 800 ng/ml) and mycophenolic acid (MPA) therapy. Results Six months after transplantation, two patients (4%) developed NODM and one patient (2%) developed AR. Four patients had impaired fasting glucose tolerance based on 75-g oral glucose tolerance testing (OGTT). There was one patient death. There were no episodes of cytomegalovirus (CMV) infection or BK virus nephritis. In contrast, in a historical cohort of n = 27 patients treated with Thymoglobulin induction, and conventional doses of cyclosporine and corticosteroids, the incidence of NODM and AR was 18% and 15%. Conclusions The pilot study results suggest that Thymoglobulin induction combined with early steroid reduction, reduced cyclosporine exposure and MPA, may reduce the incidence of both NODM and AR in low immunological risk patients. A future controlled study enriched for patients at high risk for NODM is under consideration. Trial registration ClinicalTrials.gov: http://NCT00706680 PMID:23369458

  20. Acute Antibody-Mediated Rejection in Presence of MICA-DSA and Successful Renal Re-Transplant with Negative-MICA Virtual Crossmatch

    PubMed Central

    Ming, Yingzi; Hu, Juan; Luo, Qizhi; Ding, Xiang; Luo, Weiguang; Zhuang, Quan; Zou, Yizhou

    2015-01-01

    The presence of donor-specific alloantibodies (DSAs) against the MICA antigen results in high risk for antibody-mediated rejection (AMR) of a transplanted kidney, especially in patients receiving a re-transplant. We describe the incidence of acute C4d+ AMR in a patient who had received a first kidney transplant with a zero HLA antigen mismatch. Retrospective analysis of post-transplant T and B cell crossmatches were negative, but a high level of MICA alloantibody was detected in sera collected both before and after transplant. The DSA against the first allograft mismatched MICA*018 was in the recipient. Flow cytometry and cytotoxicity tests with five samples of freshly isolated human umbilical vein endothelial cells demonstrated the alloantibody nature of patient’s MICA-DSA. Prior to the second transplant, a MICA virtual crossmatch and T and B cell crossmatches were used to identify a suitable donor. The patient received a second kidney transplant, and allograft was functioning well at one-year follow-up. Our study indicates that MICA virtual crossmatch is important in selection of a kidney donor if the recipient has been sensitized with MICA antigens. PMID:26024219

  1. Heat storage rate and acute fatigue in rats.

    PubMed

    Rodrigues, L O C; Oliveira, A; Lima, N R V; Machado-Moreira, C A

    2003-01-01

    Thermal environmental stress can anticipate acute fatigue during exercise at a fixed intensity (%VO2max). Controversy exists about whether this anticipation is caused by the absolute internal temperature (Tint, degrees C), by the heat storage rate (HSR, cal/min) or by both mechanisms. The aim of the present study was to study acute fatigue (total exercise time, TET) during thermal stress by determining Tint and HSR from abdominal temperature. Thermal environmental stress was controlled in an environmental chamber and determined as wet bulb globe temperature ( degrees C), with three environmental temperatures being studied: cold (18 degrees C), thermoneutral (23.1 degrees C) or hot (29.4 degrees C). Six untrained male Wistar rats weighing 260-360 g were used. The animals were submitted to exercise at the same time of day in the three environments and at two treadmill velocities (21 and 24 m/min) until exhaustion. After implantation of a temperature sensor and treadmill adaptation, the animals were submitted to a Latin square experimental design using a 2 x 3 factorial scheme (velocity and environment), with the level of significance set at P<0.05. The results showed that the higher the velocity and the ambient temperature, the lower was the TET, with these two factors being independent. This result indicated that fatigue was independently affected by both the increase in exercise intensity and the thermal environmental stress. Fatigue developed at different Tint and HSR showed the best inverse relationship with TET. We conclude that HSR was the main anticipating factor of fatigue. PMID:12532237

  2. Treating humoral rejection after cardiac transplantation.

    PubMed

    Verheyen, Jef; Vermeulen, Tom; Janssen Van Doorn, Karin; Vrints, Christiaan; Conraads, Viviane

    2011-04-01

    Whereas effective strategies are available to treat acute cellular cardiac rejection, humoral rejection, also called vascular or antibody-mediated rejection, is more difficult to manage. Antibody-mediated (non-cellular) rejections (AMR) are rare and few successfully treated cases have been described in the literature. We report on a female patient, diagnosed with humoral rejection, leading to severe ventricular dysfunction and haemodynamic compromise, two months after transplantation. The patient received a combination therapy, consisting of plasmapheresis and immunoglobulins, which resulted in complete resolution of immunohistochemical signs of AMR. In this report, we will overview AMR and discuss several treatment modalities. PMID:21591590

  3. Lifeline electric rates and alternative approaches to the problems of low-income ratepayers: ten case studies of rejected programs

    SciTech Connect

    Not Available

    1980-07-01

    This volume, Volume 3, contains ten case studies of non-implemented programs. It is noted that in Volume 2, the implemented lifeline programs, evolved as policy closely after the 1973 oil embargo; in contrast, the rejected programs were initiated about 4 years later and considered in a more-complex policy environment - after which time alternate methods of assisting low-income people had been developed. Specifically presented here are program summary, issue development, governmental process, and impact for the following: (a) Delaware Senate Bill 202; (b) Illinois House Bill 83; (c) Maine Legislative Document No. 1043; (d) Minnesota House File 1243; (e) New York Assembly Bill 12214; (f) New York Senate Bill 7013-A; (g) Rhode Island Resolution 79-H 5770-A; (h) South Dakota Senate Joint Resolution 9; (i) West Virginia House Bill 943; and (j) Wisconsin Assembly Bill 1250. 4 figures, 24 tables.

  4. RNAi-mediated silencing of HLA A2 suppressed acute rejection against human fibroblast xenografts in the striatum of 6-OHDA lesioned rats.

    PubMed

    Liang, Caixia; Xu, Yunzhi; Zheng, Deyu; Sun, Xiaohong; Xu, Qunyuan; Duan, Deyi

    2016-08-15

    Major histocompatibility complex class l (MHC I) molecules play a role in determining whether transplanted cells will be accepted or rejected, and masking of MHC I on donor cells has been found useful for immunoprotection of neural xenografts. In the present study, primary human embryonic lung fibroblasts (HELF), HELF treated with lentivirus-mediated small interfering RNAs (siRNAs) targeting human leukocyte antigen A2 (HLA A2, MHC I in humans) (siHELF), and rat embryonic lung fibroblasts (RELF) were stereotaxically grafted into the striatum of 6-hydroxydopamine lesioned rats to explore whether knockdown of HLA A2 could reduce host immune responses against xenografts. Before lentiviral infection, the cells were transduced with retroviruses harboring tyrosine hydroxylase cDNA. Knockdown of HLA A2 protein was examined by Western blotting. The immune responses (the number of CD4 and CD8 T-cells in the brain and peripheral blood), glial reaction, and survival of human fibroblasts were quantitatively evaluated by flow cytometry and immunohistochemistry at 4d, 2w, and 6w post-graft. Animal behaviors were assessed by counting apomorphine-induced rotations pre- and post-grafts. It was shown that a lower level of HLA A2 was observed in siHELF grafts than in HELF grafts, and knockdown of HLA A2 decreased rat immune responses, as indicated by less remarkable increases in the number of CD8 and CD4 T-cells in the brain and the ratio of CD4:CD8 T-cells in the peripheral blood in rats grafted with siHELF. Rats grafted with siHELF exhibited a significant improvement in motor asymmetry post-transplantation and a better survival of human fibroblasts at 2w. The increasing number of activated microglia and the decreasing number of astrocytes were found in three groups of rats post-implantation. These data suggested that RNAi-mediated knockdown of HLA A2 could suppress acute rejection against xenogeneic human cell transplants in the rat brain. PMID:27397073

  5. Nicotine Acutely Inhibits Erectile Tumescence by Altering Heart Rate Variability

    PubMed Central

    Harte, Christopher B.

    2014-01-01

    Objective To examine potential mechanisms underlying nicotine’s effects on male sexual arousal by exploring the mediating role of heart rate variability (HRV). Methods The sample comprised 22 healthy, nicotine-naïve men (Mage = 20.91 years; SD = 2.43). Data were taken from a double-blind, randomized, placebo-controlled, crossover trial previously completed and published elsewhere. During each laboratory visit, time-domain parameters of HRV (standard deviation of normal-to-normal [NN] intervals [SDNN], square root of the mean squared difference of successive NN intervals [RMSSD], percent of NN intervals for which successive heartbeat intervals differed by at least 50 ms [pNN50]) were assessed, as well as objective (via penile plethysmography) and subjective indices of sexual arousal. Results Acute nicotine ingestion (compared to placebo) was associated with dysregulated sympathovagal balance, which in turn was related to relatively reduced erectile tumescence. HRV did not mediate relations between nicotine intake and self-reported indices of sexual arousal. Conclusions HRV mediated the association between nicotine ingestion and erectile capacity. Findings suggest that dysfunctional cardiac autonomic tone may be an underlying mechanism by which nicotine exerts its deleterious effects on erectile health. PMID:24642073

  6. Renal allograft rejection: sonography and scintigraphy

    SciTech Connect

    Singh, A.; Cohen, W.N.

    1980-07-01

    A total of 30 renal allograft patients who had sonographic B scanning and radionuclide studies of the transplant was studied as to whether: (1) the allograft rejection was associated with any consistent and reliable sonographic features and (2) the sonograms complemented the radionuclide studies. Focal areas of decreased parenchymal echogenicity were the most striking and consistent sonographic finding in chymal echogenicity were the most striking and consistens sonographic finding in allograft rejection. This was observed in most of the patients exhibiting moderate or severe rejection, but was frequently absent with mild rejection. Areas of decreased parenchymal echogenicity were not seen during episodes of acute tubular necrosis. Therefore, sonography showing zones of decreased parenchymal echogenicity was complementary to radionuclide studies in the diagnosis of allograft rejection versus acute tubular necrosis. Corticomedullary demarcation was difficult to interpret because of technical variables, and was inconsistently related to rejection in this series.

  7. Heart rate analysis by sparse representation for acute pain detection.

    PubMed

    Tejman-Yarden, Shai; Levi, Ofer; Beizerov, Alex; Parmet, Yisrael; Nguyen, Tu; Saunders, Michael; Rudich, Zvia; Perry, James C; Baker, Dewleen G; Moeller-Bertram, Tobias

    2016-04-01

    Objective pain assessment methods pose an advantage over the currently used subjective pain rating tools. Advanced signal processing methodologies, including the wavelet transform (WT) and the orthogonal matching pursuit algorithm (OMP), were developed in the past two decades. The aim of this study was to apply and compare these time-specific methods to heart rate samples of healthy subjects for acute pain detection. Fifteen adult volunteers participated in a study conducted in the pain clinic at a single center. Each subject's heart rate was sampled for 5-min baseline, followed by a cold pressor test (CPT). Analysis was done by the WT and the OMP algorithm with a Fourier/Wavelet dictionary separately. Data from 11 subjects were analyzed. Compared to baseline, The WT analysis showed a significant coefficients' density increase during the pain incline period (p < 0.01) and the entire CPT (p < 0.01), with significantly higher coefficient amplitudes. The OMP analysis showed a significant wavelet coefficients' density increase during pain incline and decline periods (p < 0.01, p < 0.05) and the entire CPT (p < 0.001), with suggestive higher amplitudes. Comparison of both methods showed that during the baseline there was a significant reduction in wavelet coefficient density using the OMP algorithm (p < 0.001). Analysis by the two-way ANOVA with repeated measures showed a significant proportional increase in wavelet coefficients during the incline period and the entire CPT using the OMP algorithm (p < 0.01). Both methods provided accurate and non-delayed detection of pain events. Statistical analysis proved the OMP to be by far more specific allowing the Fourier coefficients to represent the signal's basic harmonics and the wavelet coefficients to focus on the time-specific painful event. This is an initial study using OMP for pain detection; further studies need to prove the efficiency of this system in different settings. PMID:26264057

  8. Prevention trumps treatment of antibody-mediated transplant rejection

    PubMed Central

    Knechtle, Stuart J.; Kwun, Jean; Iwakoshi, Neal

    2010-01-01

    Belying the spectacular success of solid organ transplantation and improvements in immunosuppressive therapy is the reality that long-term graft survival rates remain relatively unchanged, in large part due to chronic and insidious alloantibody-mediated graft injury. Half of heart transplant recipients develop chronic rejection within 10 years — a daunting statistic, particularly for young patients expecting to achieve longevity by enduring the rigors of a transplant. The current immunosuppressive pharmacopeia is relatively ineffective in preventing late alloantibody-associated chronic rejection. In this issue of the JCI, Kelishadi et al. report that preemptive deletion of B cells prior to heart transplantation in cynomolgus monkeys, in addition to conventional posttransplant immunosuppressive therapy with cyclosporine, markedly attenuated not only acute graft rejection but also alloantibody elaboration and chronic graft rejection. The success of this preemptive strike implies a central role for B cells in graft rejection, and this approach may help to delay or prevent chronic rejection after solid organ transplantation. PMID:20335653

  9. Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90%) of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab) improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. Methods/Design The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. Discussion It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. Trial registration Clinical trials gov. number: NCT01117662 PMID:23101480

  10. Estimation of the prevalence and rate of acute transfusion reactions occurring in Windhoek, Namibia

    PubMed Central

    Meza, Benjamin P.L.; Lohrke, Britta; Wilkinson, Robert; Pitman, John P.; Shiraishi, Ray W.; Bock, Naomi; Lowrance, David W.; Kuehnert, Matthew J.; Mataranyika, Mary; Basavaraju, Sridhar V.

    2014-01-01

    Background Acute transfusion reactions are probably common in sub-Saharan Africa, but transfusion reaction surveillance systems have not been widely established. In 2008, the Blood Transfusion Service of Namibia implemented a national acute transfusion reaction surveillance system, but substantial under-reporting was suspected. We estimated the actual prevalence and rate of acute transfusion reactions occurring in Windhoek, Namibia. Methods The percentage of transfusion events resulting in a reported acute transfusion reaction was calculated. Actual percentage and rates of acute transfusion reactions per 1,000 transfused units were estimated by reviewing patients’ records from six hospitals, which transfuse >99% of all blood in Windhoek. Patients’ records for 1,162 transfusion events occurring between 1st January – 31st December 2011 were randomly selected. Clinical and demographic information were abstracted and Centers for Disease Control and Prevention National Healthcare Safety Network criteria were applied to categorize acute transfusion reactions1. Results From January 1 – December 31, 2011, there were 3,697 transfusion events (involving 10,338 blood units) in the selected hospitals. Eight (0.2%) acute transfusion reactions were reported to the surveillance system. Of the 1,162 transfusion events selected, medical records for 785 transfusion events were analysed, and 28 acute transfusion reactions were detected, of which only one had also been reported to the surveillance system. An estimated 3.4% (95% confidence interval [CI]: 2.3–4.4) of transfusion events in Windhoek resulted in an acute transfusion reaction, with an estimated rate of 11.5 (95% CI: 7.6–14.5) acute transfusion reactions per 1,000 transfused units. Conclusion The estimated actual rate of acute transfusion reactions is higher than the rate reported to the national haemovigilance system. Improved surveillance and interventions to reduce transfusion-related morbidity and mortality

  11. Antibody-Mediated Lung Transplant Rejection

    PubMed Central

    Hachem, Ramsey

    2012-01-01

    Antibody-mediated rejection after lung transplantation remains enigmatic. However, emerging evidence over the past several years suggests that humoral immunity plays an important role in allograft rejection. Indeed, the development of donor-specific antibodies after transplantation has been identified as an independent risk factor for acute cellular rejection and bronchiolitis obliterans syndrome. Furthermore, cases of acute antibody-mediated rejection resulting in severe allograft dysfunction have been reported, and these demonstrate that antibodies can directly injure the allograft. However, the incidence and toll of antibody-mediated rejection are unknown because there is no widely accepted definition and some cases may be unrecognized. Clearly, humoral immunity has become an important area for research and clinical investigation. PMID:23002428

  12. High expression of CD38, CD69, CD95 and CD154 biomarkers in cultured peripheral T lymphocytes correlates with an increased risk of acute rejection in liver allograft recipients.

    PubMed

    Boix, Francisco; Millan, Olga; Segundo, David San; Mancebo, Esther; Rimola, Antoni; Fabrega, Emilio; Fortuna, Virginia; Mrowiec, Anna; Castro-Panete, Maria J; Peña, Jesus de la; Llorente, Santiago; Minguela, Alfredo; Bolarin, Jose M; Paz-Artal, Estela; Lopez-Hoyos, Marcos; Brunet, Mercé; Muro, Manuel

    2016-05-01

    The mayor goal still outstanding into the solid organ transplantation field involves the search of surrogate biomarkers able to predict several clinical events, such as acute rejection (AR) or opportunistic infection. In the present multicenter study, a series of interesting surface antigens with important activator or inhibitory immune functions on cultured peripheral T cells were monitored in liver transplant recipients drawn at baseline and up to one year after transplantation. Sixty-four patients were included in the multicenter study during 3 years. Pre- and post-transplantation surface antigens levels displayed significant differences between AR and non acute rejection (NAR) groups, and also this differential expression was used to construct a risk predictive model based on a composite panel of outcome biomarkers (CD38, CD69, CD95 and CD154). The model was able to stratify these patients at high risk of AR. These preliminary results could provide basic information to improve the immunosuppressive treatment and it might better help to predict AR episodes. PMID:26850323

  13. Acute sensitivity of landslide rates to initial soil porosity

    USGS Publications Warehouse

    Iverson, R.M.; Reid, M.E.; Iverson, N.R.; LaHusen, R.G.; Logan, M.; Mann, J.E.; Brien, D.L.

    2000-01-01

    Some landslides move imperceptibly downslope, whereas others accelerate catastrophically. Experimental landslides triggered by rising pore water pressure moved at sharply contrasting rates due to small differences in initial porosity. Wet sandy soil with porosity of about 0.5 contracted during slope failure, partially liquefied, and accelerated within 1 second to speeds over I meter per second. The same soil with porosity of about 0.4 dilated during failure and supped episodically at rates averaging 0.002 meter per second. Repeated slip episodes were induced by gradually rising pore water pressure and were arrested by pore dilation and attendant pore pressure decline.

  14. Acute Effect of Decaffeinated Coffee on Heart Rate, Blood Pressure, and Exercise Performance in Healthy Subjects

    PubMed Central

    Prakash, Ravi; Kaushik, Vidya S.

    1988-01-01

    The effect of decaffeinated coffee on the cardiovascular exercise performance in nine healthy volunteers was evaluated in a double-blind randomized fashion. The heart rate, blood pressure, and duration of exercise were unchanged, and no arrhythmias or ischemic changes were seen on the electrocardiogram after drinking decaffeinated coffee. It was concluded that decaffeinated coffee has no discernible, acute, adverse cardiovascular effects. PMID:3339645

  15. Acute and training effects of resistance exercise on heart rate variability.

    PubMed

    Kingsley, J Derek; Figueroa, Arturo

    2016-05-01

    Heart rate variability (HRV) has been used as a non-invasive method to evaluate heart rate (HR) regulation by the parasympathetic and sympathetic divisions of the autonomic nervous system. In this review, we discuss the effect of resistance exercise both acutely and after training on HRV in healthy individuals and in those with diseases characterized by autonomic dysfunction, such as hypertension and fibromyalgia. HR recovery after exercise is influenced by parasympathetic reactivation and sympathetic recovery to resting levels. Therefore, examination of HRV in response to acute exercise yields valuable insight into autonomic cardiovascular modulation and possible underlying risk for disease. Acute resistance exercise has shown to decrease cardiac parasympathetic modulation more than aerobic exercise in young healthy adults suggesting an increased risk for cardiovascular dysfunction after resistance exercise. Resistance exercise training appears to have no effect on resting HRV in healthy young adults, while it may improve parasympathetic modulation in middle-aged adults with autonomic dysfunction. Acute resistance exercise appears to decrease parasympathetic activity regardless of age. This review examines the acute and chronic effects of resistance exercise on HRV in young and older adults. PMID:25524332

  16. Heart rate and heart-rate variability responses to acute and chronic stress in a wild-caught passerine bird.

    PubMed

    Cyr, Nicole E; Dickens, Molly J; Romero, L Michael

    2009-01-01

    The cardiovascular-stress response has been studied extensively in laboratory animals but has been poorly studied in naturally selected species. We determined the relative roles of the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS) in regulating stress-induced changes in heart rate (HR) in wild-caught European starlings (Sturnus vulgaris). In both heart-rate variability (HRV) analysis and receptor blockade (atropine and propranolol) experiments, baseline HR was controlled predominantly by the PNS, whereas the increase in HR resulting from acute restraint stress was controlled predominantly by the SNS. These results indicate similar cardiac control of baseline and acute-stress-induced HR in wild-caught starlings and mammals. We further investigated HR responses during chronic stress. Driven primarily by changes in PNS regulation, baseline HR increased during the day but decreased at night. In addition, elevated HRs during acute restraint stress were attenuated throughout chronic stress and were accompanied by decreased HRV. This suggested that increased SNS drive elevated HR, but the attenuated HR response combined with resistance to the SNS blocker propranolol suggested that the sympathetic signal was less effective during chronic stress. Overall, chronic stress in wild-caught starlings elicited profound changes in cardiac function that were primarily regulated by changes in the PNS. PMID:19115847

  17. Corneal Graft Rejection Ten Years after Penetrating Keratoplasty in the Cornea Donor Study

    PubMed Central

    Dunn, Steven P.; Gal, Robin L.; Kollman, Craig; Raghinaru, Dan; Dontchev, Mariya; Blanton, Christopher L.; Holland, Edward J; Lass, Jonathan H.; Kenyon, Kenneth R.; Mannis, Mark J; Mian, Shahzad I.; Rapuano, Christopher J.; Stark, Walter J.; Beck, Roy W.

    2015-01-01

    Purpose To assess the effect of donor and recipient factors on corneal allograft rejection and evaluate whether a rejection event was associated with graft failure. Methods 1,090 subjects undergoing penetrating keratoplasty for a moderate risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema) were followed for up to 12 years. Associations of baseline recipient and donor factors with the occurrence of a rejection event were assessed in univariate and multivariate proportional hazards models. Results Among 651 eyes with a surviving graft at 5 years, the 10-year graft failure (± 99% CI) rates were 12% ± 4% among eyes with no rejection events in the first 5 years, 17% ± 12% in eyes with at least one probable, but no definite rejection event, and 22% ± 20% in eyes with at least one definite rejection event. The only baseline factor significantly associated with a higher risk of definite graft rejection was a preoperative history of glaucoma, particularly when prior glaucoma surgery had been performed and glaucoma medications were being used at time of transplant (10-year incidence 35% ± 23% compared with 14% ± 4% in eyes with no history of glaucoma/intraocular pressure treatment, p=0.008). Conclusion Those patients who experienced a definite rejection event frequently went on to graft failure raising important questions as to how we might change acute and long-term corneal graft management. Multivariate analysis indicated that the prior use of glaucoma medications and glaucoma filtering surgery was a significant risk factor related to a definite rejection event. PMID:25119961

  18. Profile of the Pleximmune blood test for transplant rejection risk prediction.

    PubMed

    Sindhi, Rakesh; Ashokkumar, Chethan; Higgs, Brandon W; Levy, Samantha; Soltys, Kyle; Bond, Geoffrey; Mazariegos, George; Ranganathan, Sarangarajan; Zeevi, Adriana

    2016-04-01

    The Pleximmune(TM) test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein-Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in a 5-year graft loss rate of up to 50%. Such outcomes seem increasingly unacceptable because children can experience rejection-free survival with reduced immunosuppression. Pleximmune test sensitivity and specificity for predicting acute cellular rejection is 84% and 80% respectively in training set-validation set testing of 214 children. Among existing gold standards, the biopsy detects but cannot predict rejection. Anti-donor antibodies, which presage antibody-mediated injury, reflect late-stage allosensitization as a downstream effect of engagement between recipient and donor cells. Therefore, durable graft and patient outcomes also require accurate management of cellular immune responses in clinical practice. PMID:26760313

  19. Opioid activity in behavioral and heart rate responses of tethered pigs to acute stress.

    PubMed

    Loijens, L W S; Janssens, C J J G; Schouten, W G P; Wiegant, V M

    2002-04-15

    In a longitudinal experiment, effects of long-term tether housing on heart rate and behavioral responses to an acute stressor (a 15-min challenge with a nosesling) were investigated in pigs. The animals were challenged during loose housing and again after 10-11 weeks of tether housing. To detect possible changes in endogenous opioid systems modifying these responses, the pigs were pretreated with the opioid receptor antagonist naloxone (0.5 mg/kg body weight, iv). In response to the nosesling challenge, the animals showed pronounced resistance behavior and a sharp rise in heart rate. Following this initial phase of resistance, the heart rate dropped to prechallenge levels or below this line, and the pigs seemed to become sedated. Pretreatment with naloxone increased the heart rate response in animals that were long-term tether housed (n=12). No such effect was found in the control group (n=5) that was loose-housed during the entire experiment, indicating that the impact of endogenous opioid systems mitigating heart rate responses to acute stress had increased as a result of long-term tether housing. Changes in the effect of naloxone on the behavioral response were not found. Adaptive changes in opioid systems may prevent excessive physiological reactions to acute stress and, thus, may serve as a coping mechanism. PMID:12020727

  20. Use of Electrodeposition for Sample Preparation and Rejection Rate Prediction for Assay of Electroformed Ultra High Purity Copper for 232Th and 238U Prior to Inductively Coupled Plasma Mass Spectrometry (ICP/MS)

    SciTech Connect

    Hoppe, Eric W.; Aalseth, Craig E.; Brodzinski, Ronald L.; Day, Anthony R.; Farmer, Orville T.; Hossbach, Todd W.; McIntyre, Justin I.; Miley, Harry S.; Mintzer, Esther E.; Seifert, Allen; Smart, John E.; Warren, Glen A.

    2008-07-01

    The search for neutrinoless double beta decay in 76Ge has driven the need for ultra-low background Ge detectors shielded by electroformed copper of ultra-high radiopurity (<0.1µBq/kg). Although electrodeposition processes are almost sophisticated enough to produce copper of this purity, to date there are no methods sensitive enough to assay it. Inductively-coupled plasma mass spectrometry (ICP/MS) can detect thorium and uranium at femtogram levels, but in the past, this assay has been hindered by high copper concentrations in the sample. Electrodeposition of copper samples removes copper from the solution while selectively concentrating thorium and uranium contaminants to be assayed by ICP/MS. Spiking 232Th and 238U into the plating bath simulates low purity copper and allows for the calculation of the electrochemical rejection rate of thorium and uranium in the electroplating system. This rejection value will help to model plating bath chemistry.

  1. HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival.

    PubMed

    Rudolph, E N; Dunn, T B; Mauer, D; Noreen, H; Sutherland, D E R; Kandaswamy, R; Finger, E B

    2016-08-01

    To enhance selection of appropriate deceased donors for pancreas transplants, we sought to determine whether HLA matching improved posttransplantation outcomes. In this single-center study of 1219 pancreas transplants, we correlated posttransplantation outcomes with HLA-A, -B, -C, -DR, and -DQ matches and mismatches. Rejection was linearly correlated with the number of mismatches. The individual number of HLA mismatches reached significance at four or more with a 2.3- to 2.9-fold increase in rejection. The effect was most predominant with HLA-B (1.8-fold with one mismatch and 2.0-fold with two mismatches) and -DR (1.9-fold with two mismatches) loci, whereas HLA-A, -C, and -DQ matches or mismatches did not independently predict acute rejection. The affect was strongest in solitary pancreas transplants, with little impact for simultaneous pancreas and kidney (SPK). In contrast, HLA matching did not affect graft or patient survival rates but was associated with a reduced risk of opportunistic infection. Avoidance of acute rejection saved an estimated $32 000 for solitary pancreas recipients and $52 000 for SPK recipients in hospital costs. Our data do not support the use of HLA matching for predicting pancreas graft survival but do support its significance for the reduction of acute rejection, particularly for solitary pancreas recipients. PMID:26814363

  2. Haptoglobin Enhances Cardiac Transplant Rejection

    PubMed Central

    Shen, Hua; Heuzey, Elizabeth; Mori, Daniel; Wong, Christine; Colangelo, Christopher; Chung, Lisa M.; Bruce, Can; Slizovskiy, Ilya B.; Booth, Carmen J.; Kreisel, Daniel; Goldstein, Daniel R.

    2015-01-01

    Rationale Early graft inflammation enhances both acute and chronic rejection of heart transplants, but it is unclear how this inflammation is initiated. Objective To identify specific inflammatory modulators and determine their underlying molecular mechanisms after cardiac transplantation. Methods and Results We used a murine heterotopic cardiac transplant model to identify inflammatory modulators of early graft inflammation. Unbiased mass spectrometric analysis of cardiac tissue before and up to 72 hours after transplantation revealed that 22 proteins including haptoglobin, a known anti-oxidant, are significantly upregulated in our grafts. Through the use of haptoglobin deficient mice, we show that 80% of haptoglobin deficient recipients treated with peri-operative administration of the costimulatory blocking agent CTLA4 immunoglobulin exhibited > 100 days survival of full major histocompatibility complex mismatched allografts, whereas all similarly treated wild type recipients rejected their transplants by 21 days post transplantation. We found that haptoglobin modifies the intra-allograft inflammatory milieu by enhancing levels of the inflammatory cytokine IL-6 and the chemokine MIP-2 but impair levels of the immunosuppressive cytokine IL-10. Haptoglobin also enhances dendritic cell graft recruitment and augments anti-donor T cell responses. Moreover, we confirmed that the protein is present in human cardiac allograft specimens undergoing acute graft rejection. Conclusions Our findings provide new insights into the mechanisms of inflammation after cardiac transplantation and suggest that, in contrast to its prior reported anti-oxidant function in vascular inflammation, haptoglobin is an enhancer of inflammation after cardiac transplantation. Haptoglobin may also be a key component in other sterile inflammatory conditions. PMID:25801896

  3. Response of lymphoid organs to low dose rate Cf-252, Cs-137 and acute Co-60

    SciTech Connect

    Feola, J.; Maruyama, Y.; Magura, C.; Hwang, H.N.

    1986-01-01

    RBE of low dose rate (LDR) /sup 252/Cf radiation was studied for thymus using weight loss compared to unirradiated controls. These were compared against LDR /sup 137/Cs and acute /sup 60/Co effects. For thymus, biexponential dose response curves were noted for acute /sup 60/Co and LDR /sup 137/Cs irradiations. No dose rate effect was noted with /sup 137/Cs. D/sub 37/ for the first component D/sub 1/ was 109 cGy and for the second D/sub 2/ was 624 cGy for /sup 60/Co. Relative biological effectiveness (RBE) is a complex endpoint and was different for the low dose (sensitive) and high dose (resistant) responses and for /sup 252/Cf. RBE/sub n/ of the sensitive portion was 1.7 and for overall was 4.0. Spleen response was also determined for the 3 radiations. Biexponential dose-response curves were also observed for resting spleen to acute /sup 60/Co and LDR /sup 137/Cs radiation. D/sub 1/ = 285 cGy and D/sub 2/ = 1538 cGy for acute /sup 60/Co; D/sub 1/ = 205 cGy for /sup 137/Cs and indicated a dose rate effect = 1.04 for /sup 137/Cs. The LDR /sup 137/Cs was 1.3x more effective than acute /sup 60/Co for the sensitive response; it was 1.9 x greater for the resistant response. However, the response to /sup 252/Cf vs. /sup 137/Cs for the spleen indicated that there was a greater sensitivity to dose rate than to LET. RBE/sub n/ for /sup 252/Cf vs. /sup 137/Cs was 1.0. Stimulation of spleen growth after injection of Corynebacterium parvum allowed study of radiation effects of proliferating spleen cells at day 10. Acute /sup 60/Co and LDR /sup 137/Cs ..gamma..-rays had reduced effects compared to LDR /sup 252/Cf radiation and RBE was 4.0 vs. LDR /sup 137/Cs. RBE in lymphoid organs thus depended on organ, on assay and on resting/proliferating status.

  4. Factors Influencing Rate of Testicular Salvage in Acute Testicular Torsion at a Tertiary Pediatric Center

    PubMed Central

    Ramachandra, Puneeta; Palazzi, Kerrin L.; Holmes, Nicholas M.; Marietti, Sarah

    2015-01-01

    Introduction Studies have demonstrated that variables other than duration of symptoms can affect outcomes in children with acute testicular torsion. We examined demographic and logistical factors, including inter-hospital transfer, which may affect outcomes at a tertiary pediatric referral center. Methods We reviewed charts of all pediatric patients with acute testicular torsion during a five-year period. Data were collected regarding age, insurance type, socioeconomic status, duration of symptoms prior to presentation, transfer status, time of day, time to surgical exploration, and testicular salvage. Results Our study included 114 patients. Testicular salvage was possible in 55.3% of patients. Thirty-one percent of patients included in the study were transferred from another facility. Inter-hospital transfer did not affect testicular salvage rate. Time to surgery and duration of pain were higher among patients who underwent orchiectomy versus orchidopexy. Patients older than eight years of age were more likely to undergo orchidopexy than those younger than eight (61.5% vs. 30.4%, p=0.01). Ethnicity, insurance type, or time of day did not affect the testicular salvage rates. On multivariate analysis, only duration of symptoms less than six hours predicted testicular salvage (OR 22.5, p<0.001). Conclusion Even though inter-hospital transfer delays definitive surgical management, it may not affect testicular salvage rates. Time to presentation is the most important factor in predicting outcomes in children with acute testicular torsion. PMID:25671040

  5. Diagnosis and Management of Antibody-Mediated Rejection: Current Status and Novel Approaches

    PubMed Central

    Djamali, A; Kaufman, D B; Ellis, T M; Zhong, W; Matas, A; Samaniego, M

    2014-01-01

    Advances in multimodal immunotherapy have significantly reduced acute rejection rates and substantially improved 1-year graft survival following renal transplantation. However, long-term (10-year) survival rates have stagnated over the past decade. Recent studies indicate that antibody-mediated rejection (ABMR) is among the most important barriers to improving long-term outcomes. Improved understanding of the roles of acute and chronic ABMR has evolved in recent years following major progress in the technical ability to detect and quantify recipient anti-HLA antibody production. Additionally, new knowledge of the immunobiology of B cells and plasma cells that pertains to allograft rejection and tolerance has emerged. Still, questions regarding the classification of ABMR, the precision of diagnostic approaches, and the efficacy of various strategies for managing affected patients abound. This review article provides an overview of current thinking and research surrounding the pathophysiology and diagnosis of ABMR, ABMR-related outcomes, ABMR prevention and treatment, as well as possible future directions in treatment. This review addresses the spectrum of antibody-mediated rejection after kidney transplantation, including its pathogenesis, risk factors, phenotypes, the revised Banff 2013 classification, treatment options, and outcomes. Also see meeting report by Haas et al on page 272. PMID:24401076

  6. Robotic CABG decreases 30-day complication rate, length of stay and acute care facility discharge rate compared to conventional surgery

    PubMed Central

    Leyvi, Galina; Forest, Stephen; Srinivas, V. S.; Greenberg, Mark; Wang, Nan; Mais, Alec; Snyder, Max; DeRose, Joseph J.

    2015-01-01

    Summary Objective The objective of this study was to compare the short term outcomes of robotic with conventional on pump coronary artery bypass grafting (CABG). Methods The study population included 2091 consecutive patients who underwent either conventional or robotic CABG from January 2007 to March 2012. Pre-operative, intra-operative and 30-day post-operative variables were collected for each group. In order to compare the incidence of rapid recovery between conventional and robotic CABG, the surrogate variables of early discharge and discharge to home (versus rehabilitation or acute care facility) were evaluated. A multivariate logistic regression analysis was utilized. Results One hundred and fifty robotic and 1,619 conventional CABG cases were analyzed. Multivariate logistic regression analysis demonstrated that robotic surgery was a strong predictor of lower 30-day complications (OR = 0.24, p=0.005), short length of stay (OR 3.31, p < 0.001), and decreased need for an acute care facility (OR 0.55, p = 0.032). In the presence of complications (NY State Complication Composite), the robotic technique was not associated with a change in discharge status. Conclusions In this retrospective review robotic CABG was associated with a lower 30-day complication rate, a shorter length of stay and a lower incidence of acute care facility discharge than conventional on pump CABG. It may suggest a more rapid recovery to pre-operative status after robotic surgery: however, only a randomized prospective study could confirm the advantages of a robotic approach PMID:25238421

  7. Agricultural adjuvants: acute mortality and effects on population growth rate of Daphnia pulex after chronic exposure.

    PubMed

    Stark, John D; Walthall, William K

    2003-12-01

    Acute and chronic toxicity of eight agricultural adjuvants (Bond, Kinetic, Plyac, R-11, Silwet L-77, Sylgard 309, X-77, and WaterMaxx) to Daphnia pulex were evaluated with 48-h acute lethal concentration estimates (LC50) and a 10-d population growth-rate measurement, the instantaneous rate of increase (r1). Based on LC50, the order of toxicity was R-11 > X-77 = Sylgard 309 = Silwet L-77 > Kinetic > Bond > Plyac > WaterMaxx; all LC50 estimates were higher than the expected environmental concentration (EEC) of 0.79 mg/L, indicating that none of these adjuvants should cause high levels of mortality in wild D. pulex populations. Extinction, defined as negative population growth rate, occurred after exposure to 0.9 mg/L R-11, 13 mg/L X-77, 25 mg/L Kinetic, 28 mg/L Silwet, 18 mg/L Sylgard, 450 mg/L Bond, 610 mg/L Plyac, and 1,600 mg/L WaterMaxx. Concentrations that caused extinction were substantially below the acute LC50 for R-11, Kinetic, Plyac, X-77, and Bond. The no-observable-effects concentration (NOEC) and lowest-observable-effects concentration (LOEC) for the number of offspring per surviving female after exposure to R-11 were 0.5 and 0.75 mg/L, respectively. The NOEC and LOEC for population size after exposure to R-11 were (1.25 and 0.5 mg/L, respectively. Both of these values were lower than the EEC, indicating that R-11 does have the potential to cause damage to D. pulex populations after application at recommended field rates. The wide range of concentrations causing extinction makes it difficult to generalize about the potential impacts that agricultural adjuvants might have on aquatic ecosystems. Therefore, additional studies that examine effects on other nontarget organisms and determine residues in aquatic ecosystems may be warranted. PMID:14713050

  8. Countering Rejection Anxiety.

    ERIC Educational Resources Information Center

    Hanselman, Peggy Riley

    1989-01-01

    Outlines a step-by-step approach for guidance counselors in holding a preliminary college planning conference with high school juniors and their families in order to help students subsequently deal with possible rejection from a college. (TE)

  9. The experimental study on heat rejection equipment

    NASA Astrophysics Data System (ADS)

    Nakagawa, Toshihiko; Atsumi, Masahiro; Tokue, Rinzo

    1992-07-01

    This paper describes the concept study and the experimental work for development of the advanced style expendable heat rejection device. Emphasis is laid on minimizing the hardware weight and using innocuous coolant. Empirical heat transfer characteristics of water spray cooling were obtained and applied to the mathematical model to evaluate the performance. Besides the development of spray nozzle, prototype model of 4 kW class evaporator was fabricated and tested. Heat rejection rate of 3.2-4.5 kW was attained at both (high/low altitude) modes of operation, and feasibility of this heat rejection device was assured.

  10. [Heart rate and outcome in patients with acute and chronic heart failure].

    PubMed

    Oliva, Fabrizio; Ammirati, Enrico; Campana, Carlo; Carubelli, Valentina; Cirò, Antonio; Di Tano, Giuseppe; Mortara, Andrea; Senni, Michele; Morandi, Fabrizio; Metra, Marco

    2016-03-01

    Heart rate (HR) is not only a physical sign but also a biomarker. High HR in several cardiac disorders is associated with increased mortality. In heart failure (HF), HR represents an important therapeutic target, both in the acute and chronic phase. Beta-blockers are a milestone of recommended treatments in HF patients with reduced ejection fraction. However, hemodynamic profile or intolerance may limit the use or the optimization of beta-blocker treatment, both during hospitalization and outpatient follow-up. More recently, ivabradine has become available, a drug that lowers HR by blocking the I(f) current in the pacemaker cells at the sinoatrial node level. In the SHIFT trial, ivabradine was shown to improve the outcome of patients with chronic HF, in sinus rhythm, with HR >70 b/min while on beta-blockers. Preliminary data have shown that this drug has a good safety profile and lowers effectively HR even during hospitalization due to worsening HF. However, further studies are warranted to understand if an earlier administration of ivabradine can lead to a better prognosis beyond symptom control and improved hemodynamics. In patients with atrial fibrillation and HF, the target is the restoration of sinus rhythm, alternatively rate control should be pursued with beta-blockers, amiodarone or digitalis, even if there is no clear evidence of an association between ventricular rate response in patients with atrial fibrillation at discharge after an HF hospitalization and major cardiovascular events. In this review, the studies that point to a role of HR both as a biomarker and a therapeutic target in patients with acute and chronic HF are described. In addition, the proportions of patients who do not reach target HR values at discharge after an acute decompensated HF episode or in the chronic phase are evaluated based on the Italian registries. PMID:27030005

  11. Acute hypoxia increases the cerebral metabolic rate - a magnetic resonance imaging study.

    PubMed

    Vestergaard, Mark B; Lindberg, Ulrich; Aachmann-Andersen, Niels Jacob; Lisbjerg, Kristian; Christensen, Søren Just; Law, Ian; Rasmussen, Peter; Olsen, Niels V; Larsson, Henrik Bw

    2016-06-01

    The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% ([Formula: see text]), glutamate increased by 4.7% ([Formula: see text]) and creatine and phosphocreatine decreased by 15.2% (p[Formula: see text]). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia. PMID:26661163

  12. Acute hypoxia increases the cerebral metabolic rate – a magnetic resonance imaging study

    PubMed Central

    Lindberg, Ulrich; Aachmann-Andersen, Niels Jacob; Lisbjerg, Kristian; Christensen, Søren Just; Law, Ian; Rasmussen, Peter; Olsen, Niels V; Larsson, Henrik BW

    2015-01-01

    The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% (p<10-6), glutamate increased by 4.7% (p<10-4) and creatine and phosphocreatine decreased by 15.2% (p<10-3). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia. PMID:26661163

  13. Acute effects of Solanum malacoxylon on bone formation rates in growing rats.

    PubMed

    Norrdin, R W; de Barros, C S; Queille, M L; Carré, M; Miravet, L

    1979-11-01

    The plant Solanum malacoxylon is responsible for a syndrome of hypercalcemia, soft tissue mineralization, and progressive wasting in South American cattle known as enteque seco or espichamento. There is evidence that a glycoside of 1,25-dihydroxycholecalciferol is the active principle in the plant. The basis for the hyperostosis seen in the disease is unclear. To study the acute effects on bone formation rates, 8-week-old rats were given an aqueous extract equivalent to 250 or 1000 mg of Solanum daily per os for 7 days. Bones were labeled by injection of fluochrome 2 days before the start of treatment and 2 days prior to sacrifice. Morphometric evaluation of undecalcified sections of caudal vertebrae revealed an increased amount of trabecular bone in both Solanum treated groups with no difference due to dose level. This was associated with an increase in the bone apposition rate on trabecular surfaces. No differences were found in the amount of osteoid seam width. Periosteal apposition rate and endochondral bone formation were also measured and no significant differences found. The findings indicate that acute stimulation of cell level bone formation on trabecular surfaces may play a role in the hyperostosis seen in the naturally occurring condition. PMID:116737

  14. Integrin antagonists prevent costimulatory blockade-resistant transplant rejection by CD8(+) memory T cells.

    PubMed

    Kitchens, W H; Haridas, D; Wagener, M E; Song, M; Kirk, A D; Larsen, C P; Ford, M L

    2012-01-01

    The success of belatacept in late-stage clinical trials inaugurates the arrival of a new class of immunosuppressants based on costimulatory blockade, an immunosuppression strategy that disrupts essential signals required for alloreactive T-cell activation. Despite having improved renal function, kidney transplant recipients treated with belatacept experienced increased rates of acute rejection. This finding has renewed focus on costimulatory blockade-resistant rejection and specifically the role of alloreactive memory T cells in mediating this resistance. To study the mechanisms of costimulatory blockade-resistant rejection and enhance the clinical efficacy of costimulatory blockade, we developed an experimental transplant system that models a donor-specific memory CD8(+) T-cell response. After confirming that graft-specific memory T cells mediate costimulatory blockade-resistant rejection, we characterized the role of integrins in this rejection. The resistance of memory T cells to costimulatory blockade was abrogated when costimulatory blockade was coupled with either anti-VLA-4 or anti-LFA-1. Mechanistic studies revealed that in the presence of costimulatory blockade, anti-VLA-4 impaired T-cell trafficking to the graft but not memory T-cell recall effector function, whereas anti-LFA-1 attenuated both trafficking and memory recall effector function. As antagonists against these integrins are clinically approved, these findings may have significant translational potential for future clinical transplant trials. PMID:21942986

  15. Integrin antagonists prevent costimulatory blockade-resistant transplant rejection by CD8+ memory T cells

    PubMed Central

    Kitchens, W. H.; Haridas, D.; Wagener, M. E.; Song, M.; Kirk, A. D.; Larsen, C. P.; Ford, M. L.

    2012-01-01

    The success of belatacept in late-stage clinical trials inaugurates the arrival of a new class of immunosuppressants based on costimulatory blockade, an immunosuppression strategy that disrupts essential signals required for alloreactive T cell activation. Despite having improved renal function, kidney transplant recipients treated with belatacept experienced increased rates of acute rejection. This finding has renewed focus on costimulatory blockade-resistant rejection and specifically the role of alloreactive memory T cells in mediating this resistance. To study mechanisms of costimulatory blockade-resistant rejection and enhance the clinical efficacy of costimulatory blockade, we developed an experimental transplant system that models a donor-specific memory CD8+ T cell response. After confirming that graft-specific memory T cells mediate costimulatory blockade-resistant rejection, we characterized the role of integrins in this rejection. The resistance of memory T cells to costimulatory blockade was abrogated when costimulatory blockade was coupled with either anti-VLA-4 or anti-LFA-1. Mechanistic studies revealed that in the presence of costimulatory blockade, anti-VLA-4 impaired T cell trafficking to the graft but not memory T cell recall effector function, whereas anti-LFA-1 attenuated both trafficking and memory recall effector function. As antagonists against these integrins are clinically approved, these findings may have significant translational potential for future clinical transplant trials. PMID:21942986

  16. Low rate of cardiovascular events in patients with acute myocarditis diagnosed by cardiovascular magnetic resonance

    PubMed Central

    De Stefano, Luciano; Yeyati, Ezequiel Levy; Pietrani, Marcelo; Kohan, Andres; Falconi, Mariano; Benger, Juan; Dragonetti, Laura; Garcia-Monaco, Ricardo; Cagide, Arturo

    2014-01-01

    Background Myocarditis is a relatively common inflammatory disease that affects the myocardium. Infectious disease accounts for most of the cases either because of a direct viral infection or post-viral immune-mediated reaction. Cardiovascular magnetic resonance (CMR) has become an established non-invasive diagnosis tool for acute myocarditis. A recent large single centre study with patients with biopsy-proven viral myocarditis undergoing CMR scans found a high rate of mortality. The aim of this study was to assess the rate of clinical events in our population of patients with diagnosed myocarditis by CMR scan. Methods Patients who consulted to the emergency department with diagnosis of myocarditis by CMR were retrospectively included in the study from January 2008 to May 2012. A CMR protocol was used in all patients, and were followed up to assess the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or implantable cardiac defibrillator (ICD). A descriptive statistical analysis was performed. Results Thirty-two patients with myocarditis were included in the study. The mean age was 42.6±21.2 years and 81.2% were male. In a mean follow up of 30.4±17.8 months, the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or ICD was 15.6% (n=5). Two patients had heart failure (one of them underwent heart transplant), one patient needed ICD because of ventricular tachycardia and two other patients were re-hospitalized, for recurrent chest pain and for recurrent myocarditis respectively. Conclusions In our series of acute myocarditis diagnosed by CMR we found a low rate of cardiovascular events without mortality. These findings might oppose data from recently published myocarditis trials. PMID

  17. Heart rate in Palaemon northropi (Rankin) in relation to acute changes in thermal environment

    SciTech Connect

    Swanson, C.J.; Wingard, C.; Kitakis, F. )

    1991-03-15

    The Glass Shrimp (Palaemon northropi), common to shallow water/tide pool environs of Atlantic waters, was examined in a series of experiments whereby the temperature-dependence of steady-state heart rate was assessed after acute, controlled changed in their thermal environment. Collection site, tide pool variations averaged 17.2-31.6C/24 hr. period. Accordingly, steady-state heart rates were determined at 5, 15, 25, and 30C by using both timed, optical recording and impedance methods. Mean values obtained were 88bpm (5C), 181 bpm(15C), 236bpm(25C), and 52bpm(30C). Calculated Q{sub 10} determinations ranged from the limits of 1.3 to 2.1 excluding the highest temperature state used. Specimens used averaged 0.62gm wet body weight, and no significant difference between males and gravid females was found. Additionally, the impedance method employed allowed for more precise rate determinations at high heart rates: at the lower heart rates, there was no difference between optically-timed vs. impedance method. Measurement at 30C characteristically showed a severe depression of heart rate, and high mortality after determinations. It is concluded that in situ field survival of Palaemon northropi may involve a time-dependence and/or other mechanisms whereby upper environmental temperatures may be abated.

  18. When heart goes “BOOM” to fast. Heart rate greater than 80 as mortality predictor in acute myocardial infarction

    PubMed Central

    Davidovic, Goran; Iric-Cupic, Violeta; Milanov, Srdjan; Dimitijevic, Aleksandra; Petrovic-Janicijevic, Mirjana

    2013-01-01

    Many prospective studies established association between high heart rate and increased cardiovascular morbidity and mortality, independently of other risk factors. Heart rate over 80 beats per minute more often leads to atherosclerotic plaque disruption, the main step in developing acute coronary syndrome. Purpose was to investigate the incidence of higher heart rate levels in patients with anterior wall acute myocardial infarction with ST-segment elevation and the influence of heart rate on mortality. Research included 140 patients with anterior wall acute myocardial infarction with ST-segment elevation treated in Coronary Unit, Clinical Center Kragujevac in the period from January 2001-June 2006. Heart rate was calculated as the mean value of baseline and heart rate in the first 30 minutes after admission. Other risk factors were also followed to determine their connection with elevated heart rate. Results showed that the majority of patients survived (over 70%). In a total number of patients, more than 75% had a heart rate levels greater than 80 beats per minute. There was a significant difference in heart rate on addmision between survivors and patients who died, with a greater levels in patients with fatal outcome. Both, univariate and multivariate regression analysis singled out heart rate greater than 80 beats per minute as independent mortality predictor in these patients. Heart rate greater than 80 beats per minute is a major, independent risk factor for morbidity and important predictor of mortality in patients with acute myocardial infarction. PMID:23991346

  19. Image rejects in general direct digital radiography

    PubMed Central

    Rosanowsky, Tine Blomberg; Jensen, Camilla; Wah, Kenneth Hong Ching

    2015-01-01

    Background The number of rejected images is an indicator of image quality and unnecessary imaging at a radiology department. Image reject analysis was frequent in the film era, but comparably few and small studies have been published after converting to digital radiography. One reason may be a belief that rejects have been eliminated with digitalization. Purpose To measure the extension of deleted images in direct digital radiography (DR), in order to assess the rates of rejects and unnecessary imaging and to analyze reasons for deletions, in order to improve the radiological services. Material and Methods All exposed images at two direct digital laboratories at a hospital in Norway were reviewed in January 2014. Type of examination, number of exposed images, and number of deleted images were registered. Each deleted image was analyzed separately and the reason for deleting the image was recorded. Results Out of 5417 exposed images, 596 were deleted, giving a deletion rate of 11%. A total of 51.3% were deleted due to positioning errors and 31.0% due to error in centering. The examinations with the highest percentage of deleted images were the knee, hip, and ankle, 20.6%, 18.5%, and 13.8% respectively. Conclusion The reject rate is at least as high as the deletion rate and is comparable with previous film-based imaging systems. The reasons for rejection are quite different in digital systems. This falsifies the hypothesis that digitalization would eliminates rejects. A deleted image does not contribute to diagnostics, and therefore is an unnecessary image. Hence, the high rates of deleted images have implications for management, training, education, as well as for quality. PMID:26500784

  20. Family directed umbilical cord blood banking for acute leukemia: usage rate in hematopoietic stem cell transplantation.

    PubMed

    Screnci, M; Murgi, E; Tamburini, A; Pecci, M R; Ballatore, G; Cusanno, A; Valle, V; Luciani, P; Corona, F; Girelli, G

    2015-04-01

    Family-directed umbilical cord blood (UCB) collection and banking is indicated in women delivering healthy babies who already have a member of their own family with a disease potentially treatable with an allogeneic hematopoietic stem cell (HSCs) transplantation (HSCT). The rapid availability of UCB is an important issue in HSCs procurement particularly for recipients with acute leukemia who urgently need HSCT. The aims of this study were to assess the usage rate of family UCB collections directed to patients with acute leukemia and to investigate the factors influencing the usage rate. A total of 113 families were enrolled, 118 UCB units were successfully collected and one collection failed due to emergency occurred during delivery. Among these, 7 collections were required for children who were in urgent need of a transplant: three HLA-matched units were successfully transplanted, respectively after 2, 5 and 6 months from collection; three collections resulted HLA-mismatched, while HLA-typing is pending for one unit. The remaining collections were mostly required for potential future use, among these units only one was transplanted in a HLA compatible sibling after 3 years and 4 months from collection. After a median time of storage of 8.5 years (range 0.1-20 years) a total of 4/118 (3.4 %) collection has been transplanted. During this time interval, considering only patients who have had the need of a transplant, the main factor influencing low utilization rate of UCB collections was due to HLA disparity, indeed among typed UCB unit mostly (77 %) resulted HLA mismatched with the intended recipient. PMID:25504378

  1. Dynamic regulation of heart rate during acute hypotension: new insight into baroreflex function

    NASA Technical Reports Server (NTRS)

    Zhang, R.; Behbehani, K.; Crandall, C. G.; Zuckerman, J. H.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

    2001-01-01

    To examine the dynamic properties of baroreflex function, we measured beat-to-beat changes in arterial blood pressure (ABP) and heart rate (HR) during acute hypotension induced by thigh cuff deflation in 10 healthy subjects under supine resting conditions and during progressive lower body negative pressure (LBNP). The quantitative, temporal relationship between ABP and HR was fitted by a second-order autoregressive (AR) model. The frequency response was evaluated by transfer function analysis. Results: HR changes during acute hypotension appear to be controlled by an ABP error signal between baseline and induced hypotension. The quantitative relationship between changes in ABP and HR is characterized by a second-order AR model with a pure time delay of 0.75 s containing low-pass filter properties. During LBNP, the change in HR/change in ABP during induced hypotension significantly decreased, as did the numerator coefficients of the AR model and transfer function gain. Conclusions: 1) Beat-to-beat HR responses to dynamic changes in ABP may be controlled by an error signal rather than directional changes in pressure, suggesting a "set point" mechanism in short-term ABP control. 2) The quantitative relationship between dynamic changes in ABP and HR can be described by a second-order AR model with a pure time delay. 3) The ability of the baroreflex to evoke a HR response to transient changes in pressure was reduced during LBNP, which was due primarily to a reduction of the static gain of the baroreflex.

  2. SOC REJECTION BY NANOFILTRATION

    EPA Science Inventory

    A study was conducted to evaluate the rejection of six synthetic organic compounds (SOCs) from a potable water source by a nanofiltration membrane process. The S0Cs were ethylene dibromide (EDB), dibromochloropropane (DBCP), chlordane, heptachlor, methoxychlor and alachlor. To in...

  3. "Science" Rejects Postmodernism.

    ERIC Educational Resources Information Center

    St. Pierre, Elizabeth Adams

    2002-01-01

    The National Research Council report, "Scientific Research in Education," claims to present an inclusive view of sciences in responding to federal attempts to legislate educational research. This article asserts that it narrowly defines science as positivism and methodology as quantitative, rejecting postmodernism and omitting other theories. Uses…

  4. Hospital Strategies for Reducing Risk-Standardized Mortality Rates in Acute Myocardial Infarction

    PubMed Central

    Bradley, Elizabeth H.; Curry, Leslie A.; Spatz, Erica S.; Herrin, Jeph; Cherlin, Emily J.; Curtis, Jeptha P.; Thompson, Jennifer W.; Ting, Henry H.; Wang, Yongfei; Krumholz, Harlan M.

    2012-01-01

    Background Despite recent improvements in survival after acute myocardial infarction (AMI), U.S. hospitals vary 2-fold in their 30-day risk-standardized mortality rates (RSMRs). Nevertheless, information is limited on hospital-level factors that may be associated with RSMRs. Objective To identify hospital strategies that were associated with lower RSMRs. Design Cross-sectional survey of 537 hospitals (91% response rate) and weighted multivariate regression by using data from the Centers for Medicare & Medicaid Services to determine the associations between hospital strategies and hospital RSMRs. Setting Acute care hospitals with an annualized AMI volume of at least 25 patients. Participants Patients hospitalized with AMI between 1 January 2008 and 31 December 2009. Measurements Hospital performance improvement strategies, characteristics, and 30-day RSMRs. Results In multivariate analysis, several hospital strategies were significantly associated with lower RSMRs and in aggregate were associated with clinically important differences in RSMRs. These strategies included holding monthly meetings to review AMI cases between hospital clinicians and staff who transported patients to the hospital (RSMR lower by 0.70 percentage points), having cardiologists always on site (lower by 0.54 percentage points), fostering an organizational environment in which clinicians are encouraged to solve problems creatively (lower by 0.84 percentage points), not cross-training nurses from intensive care units for the cardiac catheterization laboratory (lower by 0.44 percentage points), and having physician and nurse champions rather than nurse champions alone (lower by 0.88 percentage points). Fewer than 10% of hospitals reported using at least 4 of these 5 strategies. Limitation The cross-sectional design demonstrates statistical associations but cannot establish causal relationships. Conclusion Several strategies, which are currently implemented by relatively few hospitals, are

  5. The effect of an acute bout of resistance exercise on carotid artery strain and strain rate.

    PubMed

    Black, Jane M; Stöhr, Eric J; Stone, Keeron; Pugh, Christopher J A; Stembridge, Mike; Shave, Rob; Esformes, Joseph I

    2016-09-01

    Arterial wall mechanics likely play an integral role in arterial responses to acute physiological stress. Therefore, this study aimed to determine the impact of low and moderate intensity double-leg press exercise on common carotid artery (CCA) wall mechanics using 2D vascular strain imaging. Short-axis CCA ultrasound images were collected in 15 healthy men (age: 21 ± 3 years; stature: 176.5 ± 6.2 cm; body mass; 80.6 ± 15.3 kg) before, during, and immediately after short-duration isometric double-leg press exercise at 30% and 60% of participants' one-repetition maximum (1RM: 317 ± 72 kg). Images were analyzed for peak circumferential strain (PCS), peak systolic and diastolic strain rate (S-SR and D-SR), and arterial diameter. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) were simultaneously assessed and arterial stiffness indices were calculated post hoc. A two-way repeated measures ANOVA revealed that during isometric contraction, PCS and S-SR decreased significantly (P < 0.01) before increasing significantly above resting levels post exercise (P < 0.05 and P < 0.01, respectively). Conversely, D-SR was unaltered throughout the protocol (P = 0.25). No significant differences were observed between the 30% and 60% 1RM trials. Multiple regression analysis highlighted that HR, BP, and arterial diameter did not fully explain the total variance in PCS, S-SR, and D-SR Acute double-leg press exercise is therefore associated with similar transient changes in CCA wall mechanics at low and moderate intensities. CCA wall mechanics likely provide additional insight into localized intrinsic vascular wall properties beyond current measures of arterial stiffness. PMID:27624687

  6. T3 acutely increases GH mRNA translation rate and GH secretion in hypothyroid rats.

    PubMed

    Silva, F Goulart da; Giannocco, G; Luchessi, A D; Curi, R; Nunes, M T

    2010-04-12

    Cytoskeleton controls the stability of transcripts, by mechanisms that involve mRNAs and eEF1A attachment to it. Besides, it plays a key role in protein synthesis and secretion, which seems to be impaired in somatotrophs of hypothyroid rats, whose cytoskeleton is disarranged. This study investigated the: eEF1A and GH mRNA binding to cytoskeleton plus GH mRNA translation rate and GH secretion, in sham-operated and thyroidectomized rats treated with T3 or saline, and killed 30min thereafter. Thyroidectomy reduced: (a) pituitary F-actin content, and eEF1A plus GH mRNA binding to it; (b) GH mRNA recruitment to polysome; and (c) liver IGF-I mRNA expression, indicating that GH mRNA stability and translation rate, as well as GH secretion were impaired. T3 acutely reversed all these changes, which points toward a nongenomic action of T3 on cytoskeleton rearrangement, which might contribute to the increase on GH mRNA translation rate and GH secretion. PMID:20015464

  7. Reducing conflict and containment rates on acute psychiatric wards: The Safewards cluster randomised controlled trial

    PubMed Central

    Bowers, Len; James, Karen; Quirk, Alan; Simpson, Alan; Stewart, Duncan; Hodsoll, John

    2015-01-01

    Background Acute psychiatric wards manage patients whose actions may threaten safety (conflict). Staff act to avert or minimise harm (containment). The Safewards model enabled the identification of ten interventions to reduce the frequency of both. Objective To test the efficacy of these interventions. Design A pragmatic cluster randomised controlled trial with psychiatric hospitals and wards as the units of randomisation. The main outcomes were rates of conflict and containment. Participants Staff and patients in 31 randomly chosen wards at 15 randomly chosen hospitals. Results For shifts with conflict or containment incidents, the experimental condition reduced the rate of conflict events by 15% (95% CI 5.6–23.7%) relative to the control intervention. The rate of containment events for the experimental intervention was reduced by 26.4% (95% CI 9.9–34.3%). Conclusions Simple interventions aiming to improve staff relationships with patients can reduce the frequency of conflict and containment. Trial registration IRSCTN38001825. PMID:26166187

  8. Rejection of cardiac allografts by T cells expressing a restricted repertoire of T-cell receptor V beta genes.

    PubMed Central

    Shirwan, H; Barwari, L; Cramer, D V

    1997-01-01

    We have recently shown that T cells infiltrating cardiac allografts early in graft rejection use a limited T-cell receptor (TCR) V beta repertoire. In this study we tested whether this limited repertoire of V beta genes is important for graft rejection. A cell line, AL2-L3, was established from LEW lymphocytes infiltrating ACI heart allografts 2 days after transplantation. This cell line is composed of CD4+ T cells that primarily recognize the class II RTI.B major histocompatibility complex (MHC) molecule expressed by the donor graft. This cell line precipitated acute rejection of donor hearts with a median survival time (MST) of 10.5 days following adoptive transfer to sublethally irradiated LEW recipients. This rate of graft rejection was significantly (P < 0.0007) accelerated when compared with a MST of 60 days for allografts in irradiated control recipients. The AL2-L3-mediated acceleration of graft rejection was donor specific as WF third-party heart allografts were rejected with a delayed tempo (MST = 28.5 days). The V beta repertoire of this cell line was primarily restricted to the expression of V beta 4, 15 and 19 genes. The nucleotide sequence analysis of the beta-chain cDNAs from this cell line demonstrated that the restricted use of the V gene repertoire was not shared with the N, D and J regions. A wide variety of CDR3 loops and J beta genes were used in association with selected V beta genes. These data provide evidence for the role a restricted repertoire of V beta genes plays in cardiac allograft rejection in this model. The restricted usage of the V beta repertoire in an early T-cell response to allografts may provide the opportunity to therapeutically disrupt the rejection reaction by targeting selected T-cell populations for elimination at the time of organ transplantation. Images Figure 2 PMID:9176111

  9. Combined Effects of TGFB1 +869 T/C and +915 G/C Polymorphisms on Acute Rejection Risk in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis

    PubMed Central

    Jia, Rui-Peng; Li, Ming-Hao; Gao, Xiao-Fei; Jiang, Xiao-Min; Zhu, Xian-Bo; Li, Liang-Peng; Tan, Si-Jia; Song, Qun; Li, Wen-Cheng; Zhu, Jia-Geng

    2014-01-01

    Background Transforming growth factor-beta 1(TGF-β1) is involved in the development of acute rejection (AR) episodes in solid organ transplant recipients; and a number of studies have been conducted to investigate the combined effects of human TGF-β1 gene (TGFB1) +869 T/C and +915 G/C polymorphisms on AR risk. However, the results obtained are inconclusive. Methods Eligible studies that investigated the haplotypic association between TGFB1 +869 T/C and +915 G/C polymorphisms and AR risk were comprehensively searched in the PUBMED, EMBASE, China National Knowledge Infrastructure, and Wanfang Database. Statistical analyses were performed by using STATA 12.0 and Review Manager 5.0. Results Fourteen eligible studies with 565 AR cases and 1219 non-AR cases were included. Overall, a significantly decreased risk was detected in patients carried with intermediate producer (IP) haplotypes (T/C G/C, T/T G/C, and C/C G/G) and/or low producer (LP) haplotypes (C/C G/C, C/C C/C, T/T C/C, and T/C C/C) compared with high producer (HP) haplotypes (T/T G/G and T/C G/G; IP vs. HP: OR = 0.75, 95% CI, 0.58–0.96, P heterogeneity  = 0.238; IP/LP vs. HP: OR  = 0.77, 95% CI, 0.61–0.98, P heterogeneity  = 0.144). In addition, subgroup analysis by transplant types demonstrated a similar association in patients receiving heart transplant (IP vs. HP: OR  = 0.32, 95% CI, 0.14–0.73, P heterogeneity  = 0.790; IP/LP vs. HP: OR  = 0.41, 95% CI, 0.20–0.85, P heterogeneity  = 0.320). Conclusions The current meta-analysis and systematic review indicated that recipient TGFB1 HP haplotypes were significantly associated with an increased risk for AR in solid organ transplant recipients, particularly patients receiving cardiac allograft. PMID:24705444

  10. Changes of deceleration and acceleration capacity of heart rate in patients with acute hemispheric ischemic stroke

    PubMed Central

    Xu, Yan-Hong; Wang, Xing-De; Yang, Jia-Jun; Zhou, Li; Pan, Yong-Chao

    2016-01-01

    Background and purpose Autonomic dysfunction is common after stroke, which is correlated with unfavorable outcome. Phase-rectified signal averaging is a newly developed technique for assessing cardiac autonomic function, by detecting sympathetic and vagal nerve activity separately through calculating acceleration capacity (AC) and deceleration capacity (DC) of heart rate. In this study, we used this technique for the first time to investigate the cardiac autonomic function of patients with acute hemispheric ischemic stroke. Methods A 24-hour Holter monitoring was performed in 63 patients with first-ever acute ischemic stroke in hemisphere and sinus rhythm, as well as in 50 controls with high risk of stroke. DC, AC, heart rate variability parameters, standard deviation of all normal-to-normal intervals (SDNN), and square root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals (RMSSD) were calculated. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of stroke. We analyzed the changes of DC, AC, SDNN, and RMSSD and also studied the correlations between these parameters and NIHSS scores. Results The R–R (R wave to R wave on electrocardiogram) intervals, DC, AC, and SDNN in the cerebral infarction group were lower than those in controls (P=0.003, P=0.002, P=0.006, and P=0.043), but the difference of RMSSD and the D-value and ratio between absolute value of AC (|AC|) and DC were not statistically significant compared with those in controls. The DC of the infarction group was significantly correlated with |AC|, SDNN, and RMSSD (r=0.857, r=0.619, and r=0.358; P=0.000, P=0.000, and P=0.004). Correlation analysis also showed that DC, |AC|, and SDNN were negatively correlated with NIHSS scores (r=−0.279, r=−0.266, and r=−0.319; P=0.027, P=0.035, and P=0.011). Conclusion Both DC and AC of heart rate decreased in patients with hemispheric infarction, reflecting a decrease in both vagal

  11. Liver Transplantation for Acute Intermittent Porphyria is Complicated by a High Rate of Hepatic Artery Thrombosis

    PubMed Central

    Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N

    2012-01-01

    Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the UK Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. Liver Transpl 18:195–200, 2012. © 2011 AASLD. PMID:21618697

  12. Soothing the Sting of Rejection.

    ERIC Educational Resources Information Center

    Campbell, Joan Daniels

    1990-01-01

    Preventing rejection of a student by his/her peers and helping the child to cope with such rejection are ever-present challenges for teachers. Suggestions are given by teachers who have successfully dealt with students who were rejected by classmates. (IAH)

  13. The fate of triaged and rejected manuscripts.

    PubMed

    Zoccali, Carmine; Amodeo, Daniela; Argiles, Angel; Arici, Mustafa; D'arrigo, Graziella; Evenepoel, Pieter; Fliser, Danilo; Fox, Jonathan; Gesualdo, Loreto; Jadoul, Michel; Ketteler, Markus; Malyszko, Jolanta; Massy, Ziad; Mayer, Gert; Ortiz, Alberto; Sever, Mehmet; Vanholder, Raymond; Vinck, Caroline; Wanner, Christopher; Więcek, Andrzej

    2015-12-01

    In 2011, Nephrology Dialysis and Transplantation (NDT) established a more restrictive selection process for manuscripts submitted to the journal, reducing the acceptance rate from 25% (2008-2009) to currently about 12-15%. To achieve this goal, we decided to score the priority of manuscripts submitted to NDT and to reject more papers at triage than in the past. This new scoring system allows a rapid decision for the authors without external review. However, the risk of such a restrictive policy may be that the journal might fail to capture important studies that are eventually published in higher-ranked journals. To look into this problem, we analysed random samples of papers (∼10%) rejected by NDT in 2012. Of the papers rejected at triage and those rejected after regular peer review, 59 and 61%, respectively, were accepted in other journals. A detailed analysis of these papers showed that only 4 out of 104 and 7 out of 93 of the triaged and rejected papers, respectively, were published in journals with an impact factor higher than that of NDT. Furthermore, for all these papers, independent assessors confirmed the evaluation made by the original reviewers. The number of citations of these papers was similar to that typically obtained by publications in the corresponding journals. Even though the analyses seem reassuring, previous observations made by leading journals warn that the risk of 'big misses', resulting from selective editorial policies, remains a real possibility. We will therefore continue to maintain a high degree of alertness and will periodically track the history of manuscripts rejected by NDT, particularly papers that are rejected at triage by our journal. PMID:26597920

  14. OKT3 escalating dose regimens provide effective therapy for renal allograft rejection.

    PubMed

    Woodle, E S; Bruce, D S; Josephson, M; Cronin, D; Newell, K A; Millis, J M; Piper, J B; O'Laughlin, R; Thistlethwaite, J R

    1996-08-01

    Dose-response relationships for anti-CD3 monoclonal antibody (mAb) therapy remain undefined, particularly with respect to higher dose ranges. The clinical efficacy and safety of an OKT3 dosing regimen that incorporates higher doses (escalating dose regimens) was examined in a pilot trial. Patients undergoing acute rejection were treated with a 7-d course of OKT3 in which the daily OKT3 dose was escalated during treatment course (daily doses 5, 5, 5, 5, 10, 15, 25 mg). The total amount of OKT3 given was equal to a standard 14-d course (70 mg). A total of 10 primary cadaveric renal transplant recipients were treated, and data analyzed from a median follow up of 5 months (range 3-13 months). Pre-OKT3 immunosuppressive therapy consisted of ATGAM induction therapy (n = 8), and corticosteroid rejection therapy (n = 6, 18.6 +/- 11.4 mg/kg). Median time of first rejection was 32 d (12-48 d) and median time to OKT3 was 33 d (range 15-42 d). Pre-OKT3 histology (by Banff criteria) included: mild ACR (n = 6), moderate ACR (n = 2), AVR (n = 1), ACR and acute transplant glomerulopathy (n = 1). Rejection reversal rate with escalating dose OKT3 was 100%, and each patient experienced a rapid reversal of rejection (i.e. reversal within 14 d initiation of OKT3 therapy). Six recurrent rejection episodes were diagnosed in 5 patients with a median time to recurrent rejection of 30 d following cessation of OKT3 therapy. All recurrent rejection episodes were successfully treated (FK 506 n = 4, corticosteroids n = 1, and OKT3 n = 1). CMV disease was limited to a single episode of CMV viremia in one patient. PTLD was observed in one patient who had coexisting vascular rejection at the time of PTLD diagnosis. Short- and long-term graft function is excellent (pre-rejection baseline creatinine 1.8 +/- 0.4 mg/dl, current creatinine 1.75 +/- 0.4 mg/dl). Monitoring of OKT3 serum levels revealed that patients maintained therapeutic serum levels for an average of 4 d following the last OKT3 dose

  15. Extending supplementary feeding for children younger than 5 years with moderate acute malnutrition leads to lower relapse rates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Children with moderate acute malnutrition (MAM) have a high rate of relapse and death in the year following recovery. In this pilot study, we evaluate the long-term benefits of an extended course of nutritional therapy for children with MAM. Rural Malawian children 6 to 59 months old with MAM, defin...

  16. Adding insult to injury: effects of interpersonal rejection types, rejection sensitivity, and self-regulation on obsessive relational intrusion.

    PubMed

    Sinclair, H Colleen; Ladny, Roshni T; Lyndon, Amy E

    2011-01-01

    This study tested the I(3) model [Finkel, 2007; 2008] of intimate partner violence as applied to obsessive relational intrusion (ORI) to assess the relation among self-regulation, rejection, rejection sensitivity (RS), and stalking-related aggression. In Study 1, participants (N=221) read one of three vignettes: no relationship termination, an "internal" rejection (involves an internal attribution to the rejected as cause of relationship ending), or an "external" rejection (external attributions for relationship demise). Next, participants experienced one of two conditions manipulating self-regulation (no depletion vs. depletion). Finally, participants rated their likelihood of engaging in ORI (e.g. unwanted pursuit and/or aggression). Consistent with predictions, participants receiving an internal rejection reported higher aggression than participants experiencing an external rejection, especially when depleted of self-regulation. Study 2 extended the design of Study 1 by adding in a screening survey of RS. Internal rejections still yielded more aggression than other conditions, but this was especially so when rejection-sensitive persons were depleted of self-regulation. In addition to providing support for the I(3) model of aggression, this research shows that not all types of rejection are created equal. PMID:21932334

  17. Acute Mountain Sickness, Hypoxia, Hypobaria and Exercise Duration each Affect Heart Rate.

    PubMed

    DiPasquale, D M; Strangman, G E; Harris, N S; Muza, S R

    2015-07-01

    In this study, we quantified the changes in post-exercise resting heart rate (HRrst) associated with acute mountain sickness (AMS), and compared the effects of hypobaric hypoxia (HH) and normobaric hypoxia (NH) on HRrst. We also examined the modulating roles of exercise duration and exposure time on HRrst. Each subject participated in 2 of 6 conditions: normobaric normoxia (NN), NH, or HH (4 400 m altitude equivalent) combined with either 10 or 60 min of moderate cycling at the beginning of an 8-h exposure. AMS was associated with a 2 bpm higher HRrst than when not sick, after taking into account the ambient environment, exercise duration, and SpO2. In addition, HRrst was elevated in both NH and HH compared to NN with HRrst being 50% higher in HH than in NH. Participating in long duration exercise led to elevated resting HRs (0.8-1.4 bpm higher) compared with short exercise, while short exercise caused a progressive increase in HRrst over the exposure period in both NH and HH (0.77-1.2 bpm/h of exposure). This data suggests that AMS, NH, HH, exercise duration, time of exposure, and SpO2 have independent effects on HRrst. It further suggests that hypobaria exerts its own effect on HRrst in hypoxia. Thus NH and HH may not be interchangeable environments. PMID:25837245

  18. Exposure to Discrimination and Heart Rate Variability Reactivity to Acute Stress among Women with Diabetes.

    PubMed

    Wagner, Julie; Lampert, Rachel; Tennen, Howard; Feinn, Richard

    2015-08-01

    Exposure to racial discrimination has been linked to physiological reactivity. This study investigated self-reported exposure to racial discrimination and parasympathetic [high-frequency heart rate variability (HF-HRV)] and sympathetic (norepinephrine and cortisol) activity at baseline and then again after acute laboratory stress. Lifetime exposure to racial discrimination was measured with the Schedule of Racist Events scale. Thirty-two women (16 Black and 16 White) with type 2 diabetes performed a public speaking stressor. Beat-to-beat intervals were recorded on electrocardiograph recorders, and HF-HRV was calculated using spectral analysis and natural log transformed. Norepinephrine and cortisol were measured in blood. Higher discrimination predicted lower stressor HF-HRV, even after controlling for baseline HF-HRV. When race, age, A1c and baseline systolic blood pressure were also controlled, racial discrimination remained a significant independent predictor of stressor HF-HRV. There was no association between lifetime discrimination and sympathetic markers. In conclusion, preliminary data suggest that among women with type 2 diabetes mellitus (T2DM), exposure to racial discrimination is adversely associated with parasympathetic, but not sympathetic, reactivity. PMID:24194397

  19. Heat rejection system

    DOEpatents

    Smith, Gregory C.; Tokarz, Richard D.; Parry, Jr., Harvey L.; Braun, Daniel J.

    1980-01-01

    A cooling system for rejecting waste heat consists of a cooling tower incorporating a plurality of coolant tubes provided with cooling fins and each having a plurality of cooling channels therein, means for directing a heat exchange fluid from the power plant through less than the total number of cooling channels to cool the heat exchange fluid under normal ambient temperature conditions, means for directing water through the remaining cooling channels whenever the ambient temperature rises above the temperature at which dry cooling of the heat exchange fluid is sufficient and means for cooling the water.

  20. Local allograft irradiation as an adjunct for treating severe resistant rejection after liver transplantation in adults.

    PubMed

    Ramanathan, Rajesh; Sharma, Amit; Kaspar, Matthew; Behnke, Martha; Song, Shiyu; Stravitz, R Todd; Cotterell, Adrian; Posner, Marc; Fisher, Robert A

    2015-01-01

    Acute rejection after liver transplantation occurs in one-third of all recipients and can be managed with conventional rejection therapy in the majority of cases. In rare instances, patients with severe acute rejection may be refractory to or have contraindications for conventional therapies. This case series evaluates the role of local allograft irradiation (LAI) as an adjunct for patients with rejection that is refractory to or contraindicated for conventional therapies. Additionally, the literature on the use of radiation therapy for reversing rejection in solid organ transplantation is reviewed. Five patients underwent 9 LAI treatments: 2 had refractory rejection, and 1 each had a malignancy, a concurrent life-threatening infection, and serum sickness with antibody therapy. Conventional rejection therapies included steroids, calcineurin inhibitors, and antithymocyte globulin. LAI consisted of 3 cycles of 1.5 Gy directed toward the liver allograft. Two of the 5 patients remained alive with excellent graft function. Six of the 9 treatments were successful in rescuing the liver allograft (reversing the rejection episode). Treatment success was associated with lower pretreatment serum bilirubin levels and higher pretreatment alanine aminotransferase levels. Compared with patients with immunosuppression-responsive severe acute rejection, those requiring LAI trended toward a later onset of first rejection. In conclusion, local irradiation of liver allografts can be a useful adjunct in patients for whom conventional options have been exhausted or cannot be used. The ability of LAI to reverse allograft dysfunction and promote patient survival appears to be greatest before the onset of severe cholestatic injury. PMID:25287272

  1. TLR Signals Promote IL-6/IL-17-Dependent Transplant Rejection1

    PubMed Central

    Chen, Luqiu; Ahmed, Emily; Wang, Tongmin; Wang, Ying; Ochando, Jordi; Chong, Anita S.; Alegre, Maria-Luisa

    2010-01-01

    Acute allograft rejection has often been correlated with Th1 differentiation, whereas transplantation tolerance is frequently associated with induction of regulation. The discovery of the Th17 phenotype has prompted its scrutiny in transplant rejection. Although IL-17 has recently been observed in settings of acute allograft rejection and drives rejection in T-bet-deficient mice that have impaired type 1 T cell responses, there is little evidence of its requirement during acute rejection in wild-type animals. We and others have previously shown that TLR9 signaling by exogenous CpG at the time of transplantation is sufficient to abrogate anti-CD154-mediated acceptance of fully mismatched cardiac allografts. In this study, we investigated the mechanism by which acute rejection occurs in this inflammatory context. Our results indicate that CpG targets recipient hematopoietic cells and that its pro-rejection effects correlate both with prevention of anti-CD154-mediated conversion of conventional CD4+ T cells into induced regulatory T cells (iTregs) and with the expression of IFN-γ and IL-17 by intra-graft CD4+ T cells. Moreover, the combined elimination of IL-6 and IL-17 signaling abrogated the ability of CpG to promote acute cardiac allograft rejection. Thus, pro-inflammatory signals at the time of transplantation can change the quality of the effector immune response and reveal a pathogenic function for IL-6 and IL-17 in wild-type recipients. PMID:19414775

  2. ESTIMATED RATE OF FATAL AUTOMOBILE ACCIDENTS ATTRIBUTABLE TO ACUTE SOLVENT EXPOSURE AT LOW INHALED CONCENTRATIONS

    EPA Science Inventory

    Acute solvent exposures may contribute to automobile accidents because they increase reaction time and decrease attention, in addition to impairing other behaviors. These effects resemble those of ethanol consumption, both with respect to behavioral effects and neurological mecha...

  3. Treatment advances have not improved the early death rate in acute promyelocytic leukemia

    PubMed Central

    McClellan, James Scott; Kohrt, Holbrook E.; Coutre, Steven; Gotlib, Jason R.; Majeti, Ravindra; Alizadeh, Ash A.; Medeiros, Bruno C.

    2012-01-01

    Early mortality in acute promyelocytic leukemia has been reported to occur in less than 10% of patients treated in clinical trials. This study reports the incidence and clinical features of acute promyelocytic leukemia patients treated at Stanford Hospital, CA, USA since March 1997, focusing on early mortality. We show that the risk of early death in acute promyelocytic leukemia patients is higher than previously reported. In a cohort of 70 patients who received induction therapy at Stanford Hospital, 19% and 26% died within seven and 30 days of admission, respectively. High early mortality was not limited to our institution as evaluation of the Surveillance, Epidemiology and End Results Database demonstrated that 30-day mortality for acute promyelocytic leukemia averaged 20% from 1977–2007 and did not improve significantly over this interval. Our findings show that early death is now the greatest contributor to treatment failure in this otherwise highly curable form of leukemia. PMID:21993679

  4. Hippotherapy acute impact on heart rate variability non-linear dynamics in neurological disorders.

    PubMed

    Cabiddu, Ramona; Borghi-Silva, Audrey; Trimer, Renata; Trimer, Vitor; Ricci, Paula Angélica; Italiano Monteiro, Clara; Camargo Magalhães Maniglia, Marcela; Silva Pereira, Ana Maria; Rodrigues das Chagas, Gustavo; Carvalho, Eliane Maria

    2016-05-15

    Neurological disorders are associated with autonomic dysfunction. Hippotherapy (HT) is a therapy treatment strategy that utilizes a horse in an interdisciplinary approach for the physical and mental rehabilitation of people with physical, mental and/or psychological disabilities. However, no studies have been carried out which evaluated the effects of HT on the autonomic control in these patients. Therefore, the objective of the present study was to investigate the effects of a single HT session on cardiovascular autonomic control by time domain and non-linear analysis of heart rate variability (HRV). The HRV signal was recorded continuously in twelve children affected by neurological disorders during a HT session, consisting in a 10-minute sitting position rest (P1), a 15-minute preparatory phase sitting on the horse (P2), a 15-minute HT session (P3) and a final 10-minute sitting position recovery (P4). Time domain and non-linear HRV indices, including Sample Entropy (SampEn), Lempel-Ziv Complexity (LZC) and Detrended Fluctuation Analysis (DFA), were calculated for each treatment phase. We observed that SampEn increased during P3 (SampEn=0.56±0.10) with respect to P1 (SampEn=0.40±0.14, p<0.05), while DFA decreased during P3 (DFA=1.10±0.10) with respect to P1 (DFA=1.26±0.14, p<0.05). A significant SDRR increase (p<0.05) was observed during the recovery period P4 (SDRR=50±30ms) with respect to the HT session period P3 (SDRR=30±10ms). Our results suggest that HT might benefit children with disabilities attributable to neurological disorders by eliciting an acute autonomic response during the therapy and during the recovery period. PMID:26988283

  5. Incidence Rate of Acute Encephalitis Syndrome without Specific Treatment in India and Nepal

    PubMed Central

    Potharaju, Nagabhushana Rao

    2012-01-01

    Background: A performance target (PT) for the incidence rate (IR) of acute encephalitis syndrome (AES) was not defined by the World Health Organization (WHO) due to lack of data. There is no specific treatment for ~90% of the AES cases. Objectives: (1) To determine the IR of AES not having specific treatment (AESn) in two countries, India and Nepal. (2) To suggest the PT. Subjects and Methods: This was a record-based study of the entire population of India and Nepal from 1978 to 2011. The WHO definition was used for inclusion of cases. Cases that had specific treatment were excluded. IR was calculated per 100,000 population per annum. Forecast IR was generated from 2010 to 2013 using time-series analysis. Results: There were 165,461 cases from 1978 to 2011, of which 125,030 cases were from India and 40,431 were from Nepal. The mean IR of India was 0.42 (s 0.24) and that of Nepal was 5.23 (σ 3.03). IRs of 2010 and 2011 of India and that of 2011 of Nepal were closer to the mean IR rather than the forecast IR. IR of 2010 of Nepal was closer to the forecast IR. The forecast IR for India for 2012 was 0.49 (0.19-1.06), for 2013 was 0.42 (0.15-0.97) and for Nepal for both 2012 and 2013 was 5.62 (1.53-15.05). Conclusions: IRs were considerably different for India and Nepal. Using the current mean IR as PT for the next year was simple and practical. Using forecasting was complex and, less frequently, useful. PMID:23293439

  6. Effect of trimetazidine on heart rate variability in elderly patients with acute coronary syndrome

    PubMed Central

    Zhang, Jing; He, Shenghu; Wang, Xuefei; Wang, Daxin

    2016-01-01

    Background and Objective: Trimetazidine has mainly been used in coronary insufficiency, angina and elderly myocardial infarction. However, the effect of trimetazidine on the efficacy, heart rate variability (HRV) and protection of myocardial ischemia in elderly patients with acute coronary syndrome (ACS) remains unclear. This study aimed to investigate the effect of trimetazidine on the efficacy HRV and protection of myocardial ischemia in patients with ACS. Methods: One hundred twenty two elderly ACS patients who were above 70 years were chosen and randomly divided into two groups. One group was given conventional therapy, such as aspirin, isosorbide mononitrate and fluvastatin, and the other group was administered trimetazidine in addition to conventional therapy. The treatment period was eight weeks. A PI-2.22B three-channel AECG system was used on every patient for 24 hour dynamic electrocardiogram monitoring and HRV analyses on the first day after admission and eight weeks after treatment. HRV, 24 hour RR intermediate stage standard deviation (SDNN), five minutes average normal cardiac cycle standard deviation in 24 hour (SDANN), 24 hour close together normal cardiac cycle difference value mean square root (rMSSD), the percentage of difference of close together RR intermediate > 50 ms account total RR intermediate (PNN50), high frequency (HF) and low frequency (LF) parameters of patients were observed before and after treatment. Results: The SDNN, SDANN, rMSSD, PNN50 and HF parameters significantly increased compared with the conventional treatment group (all P < 0.05). LF and LF/HF were significantly decreased in the trimetazidine treatment group compared with those in the conventional treatment group (all P < 0.05). Conclusion: Trimetazidine improves HRV of elderly ACS patients and reduces cardiovascular events. PMID:27022349

  7. A rejection method for selection of scattered states

    NASA Astrophysics Data System (ADS)

    Lawson, William S.

    1994-05-01

    A rejection method is presented that sidesteps much of the labor necessary in the usual techniques for choosing a scattered state after an electron-phonon collision with full band structure. The phonon wave number is chosen randomly, then tested to see if the resultant collision will satisfy energy conservation to within some accuracy. If not, the collision is rejected, and if so, then the wave number is adjusted in order to enforce energy conservation more precisely. The price one pays is in a high rejection rate. If the cost of a rejection is small, however, this rejection rate can be tolerated. This method will not compete with analytical models (near valley minima), but may outperform the more usual techniques. Accuracies of a few percent are practical. Simulations were preformed with the first conduction band of gallium arsenide.

  8. Acceleration of atherogenesis in ApoE−/− mice exposed to acute or low-dose-rate ionizing radiation

    PubMed Central

    Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J.; Saran, Anna

    2015-01-01

    There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE−/− mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE−/− females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response. PMID:26359350

  9. Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

    PubMed

    Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J; Saran, Anna

    2015-10-13

    There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response. PMID:26359350

  10. Autophagy in allografts rejection: A new direction?

    PubMed

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

    2016-03-18

    Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection is still a major risk for graft survival. Modulating the dosage of immunosuppressive drugs is not a good choice for all patients, new rejection mechanisms discovery are crucial to limit the inflammatory process and preserve the function of the transplant. Autophagy, a fundamental cellular process, can be detected in all subsets of lymphocytes and freshly isolated naive T lymphocytes. It is required for the homeostasis and function of T lymphocytes, which lead to cell survival or cell death depending on the context. T cell receptor (TCR) stimulation and costimulator signals induce strong autophagy, and autophagy deficient T cells leads to rampant apoptosis upon TCR stimulation. Autophagy has been proved to be activated during ischemia-reperfusion (I/R) injury and associated with grafts dysfunction. Furthermore, Autophagy has also emerged as a key mechanism in orchestrating innate and adaptive immune response to self-antigens, which relates with negative selection and Foxp3(+) Treg induction. Although, the role of autophagy in allograft rejection is unknown, current data suggest that autophagy indeed sweeps across both in the graft organs and recipients lymphocytes after transplantation. This review presents the rationale for the hypothesis that targeting the autophagy pathway could be beneficial in promoting graft survival after transplantation. PMID:26876576

  11. Design of the DRAGET Study: a multicentre controlled diagnostic study to assess the detection of acute rejection in patients with heart transplant by means of T2 quantification with MRI in comparison to myocardial biopsies

    PubMed Central

    Bonnemains, Laurent; Cherifi, Aboubaker; Girerd, Nicolas; Odille, Freddy; Felblinger, Jacques

    2015-01-01

    Introduction Patients with heart transplant are screened for silent graft rejection by recurrent endomyocardial biopsies. MRI can detect the presence of oedema non-invasively by quantitatively measuring changes of the transverse relaxation time T2 in the myocardium. Several monocentric studies have shown that T2 quantification could help detect graft rejection in a less invasive way. DRAGET is a national multicentre diagnostic study designed to prove that T2 quantification by MRI can detect graft rejection. Methods and analysis 190 patients from 10 centres will undergo T2 quantification and endomyocardial biopsy, within 24 h, 4 to 6 times during the first year after transplantation. T2 will be computed by analysing a sequence of 10 images obtained from a short-axis slice. Specific phantoms will be used to calibrate the T2 quantification on each MR scanner to cope with the different equipment (different vendors, magnetic field strength, etc). Specific pads with known T2 will also be used during each examination and provide a quality check to cope with the different experimental conditions (temperature, etc). All MRI and biopsy data will be reinterpreted in our centre and reproducibility will be assessed. The primary outcome will be sensitivity and specificity of MRI. The secondary outcomes will be (1) prognostic values of T2, (2) reproducibility of each techniques, (3) number of adverse events during each procedures and (4) confidence of the physicians in T2. Ethics and dissemination Ethics approval has been obtained. The new MRI method will be disseminated at a national level and its practical usefulness will be assessed in centres not familiar with MRI T2 quantification. The ultimate aim of the DRAGET project is to replace a strategy based solely on biopsy with one based on a first-line MRI (with biopsy only when needed) for a more efficient and less invasive detection of rejection. Trial registration numbers ANSM 2014-A00848-39, NCT02261870. PMID:26515686

  12. Accepters and Rejecters of Counseling.

    ERIC Educational Resources Information Center

    Rose, Harriett A.; Elton, Charles F.

    Personality differences between students who accept or reject proffered counseling assistance were investigated by comparing personality traits of 116 male students at the University of Kentucky who accepted or rejected letters of invitation to group counseling. Factor analysis of Omnibus Personality Inventory (OPI) scores to two groups of 60 and…

  13. Transplant rejection and paradigms lost

    PubMed Central

    Strom, Terry B.

    2013-01-01

    During transplant rejection, migrating T cells infiltrate the grafted organ, but the signals that direct this migration are incompletely understood. In this issue of the JCI, Walch et al. debunk two classical paradigms concerning transplant rejection, with important consequences for the design of antirejection therapeutics. PMID:23676457

  14. Emotional responses to interpersonal rejection.

    PubMed

    Leary, Mark R

    2015-12-01

    A great deal of human emotion arises in response to real, anticipated, remembered, or imagined rejection by other people. Because acceptance by other people improved evolutionary fitness, human beings developed biopsychological mechanisms to apprise them of threats to acceptance and belonging, along with emotional systems to deal with threats to acceptance. This article examines seven emotions that often arise when people perceive that their relational value to other people is low or in potential jeopardy, including hurt feelings, jealousy, loneliness, shame, guilt, social anxiety, and embarrassment. Other emotions, such as sadness and anger, may occur during rejection episodes, but are reactions to features of the situation other than low relational value. The article discusses the evolutionary functions of rejection-related emotions, neuroscience evidence regarding the brain regions that mediate reactions to rejection, and behavioral research from social, developmental, and clinical psychology regarding psychological and behavioral concomitants of interpersonal rejection. PMID:26869844

  15. Emotional responses to interpersonal rejection

    PubMed Central

    Leary, Mark R.

    2015-01-01

    A great deal of human emotion arises in response to real, anticipated, remembered, or imagined rejection by other people. Because acceptance by other people improved evolutionary fitness, human beings developed biopsychological mechanisms to apprise them of threats to acceptance and belonging, along with emotional systems to deal with threats to acceptance. This article examines seven emotions that often arise when people perceive that their relational value to other people is low or in potential jeopardy, including hurt feelings, jealousy, loneliness, shame, guilt, social anxiety, and embarrassment. Other emotions, such as sadness and anger, may occur during rejection episodes, but are reactions to features of the situation other than low relational value. The article discusses the evolutionary functions of rejection-related emotions, neuroscience evidence regarding the brain regions that mediate reactions to rejection, and behavioral research from social, developmental, and clinical psychology regarding psychological and behavioral concomitants of interpersonal rejection. PMID:26869844

  16. Ratios between acute aquatic toxicity and effects on population growth rates in relation to toxicant mode of action

    SciTech Connect

    Roex, E.W.M.; Gestel, C.A.M. Van; Wezel, A.P. Van; Straalen, N.M. Van

    2000-03-01

    Environmental risk assessment of chemicals is mostly based on the results of standardized toxicity tests. To obtain environmental quality criteria, extrapolation factors are used that depend on the amount and quality of available data. These extrapolation factors do not, however, take into account the mode of action of the compound tested or the life history of the test organism. In this study, the authors analyzed the variability in acute-to-chronic ratios (ACRs) for various chemicals in relation to their mode of action. Chemicals were classified as nonpolar narcotics, polar narcotics, specifically acting compounds, and heavy metals. As an acute endpoint, the LC50 was used; as a chronic endpoint, the lowest test concentration at which the natural rate of population increase (r) is affected, or LOEC(r), was used. Data were derived from the on-line literature. Nonpolar narcotic chemicals demonstrate the smallest variation in ACRs, and acute tests can be used to derive chronic endpoints for this class. For the other classes, the variation in ACRs is larger. Fish species especially show a relatively large ACR. For heavy metals, differences in the mode of action may play an important role in explaining differences in ACRs. For the other three classes, however, it is less reliable to predict chronic toxicity using the results of acute tests. In general, differences in species sensitivity rather than in mode of action for the chemical seem to determine differences in ACRs.

  17. Monitoring of corneal allograft rejection using laser flare meter

    NASA Astrophysics Data System (ADS)

    Zarnowski, Tomasz; Haszcz, Dariusz; Rakowska, Ewa; Zagorski, Zbigniew

    1998-10-01

    The purpose of this study was to quantify noninvasively, with the use of laser-flare meter the alterations of the blood-aqueous barrier following penetrating keratoplasty. This could diagnose objectively disruption of this barrier in eyes with early allograft rejection, possible even before manifestation of the clinical signs and would help to monitor the efficacy of the treatment. We used the laser flare-meter (Kowa FM-500) to investigate alteration of the blood-aqueous barrier following uncomplicated penetrating keratoplasty (PK) and in corneal allograft rejection. Examination was performed in 50 eyes of 48 patients after uncomplicated PK (7 days to 12 months after PK), in 20 normal control eyes and in 8 patients with acute allograft rejection. Flare values after uncomplicated keratoplasty slowly decreased in time reaching nearly control values 6 - 12 months postoperatively. They were considerably higher for acute allograft rejection compared to eyes following uncomplicated PK and normal control group. Actually, they tended to diminish gradually after systemic and topical administration of steroids and/or immunosuppressants. Application of laser tyndalometry has been proven to be highly useful in the follow up of patients after perforating keratoplasty-especially high risk grafts, it helps to detect objectively early allograft rejection and is beneficial in monitoring the effectiveness of the treatment.

  18. Effects of acute fresh water exposure on water flux rates and osmotic responses in Kemp's ridley sea turtles (Lepidochelys kempi)

    NASA Technical Reports Server (NTRS)

    Ortiz, R. M.; Patterson, R. M.; Wade, C. E.; Byers, F. M.

    2000-01-01

    Water flux rates and osmotic responses of Kemp's Ridley sea turtles (Lepidochelys kempi) acutely exposed to fresh water were quantified. Salt-water adapted turtles were exposed to fresh water for 4 d before being returned to salt water. During the initial salt water phase, absolute and relative water flux rates were 1.2+/-0.1 l d(-1) and 123.0+/-6.8 ml kg(-1) d(-1), respectively. When turtles were exposed to fresh water, rates increased by approximately 30%. Upon return to salt water, rates decreased to original levels. Plasma osmolality, Na(+), K(+), and Cl(-) decreased during exposure to fresh water, and subsequently increased during the return to salt water. The Na(+):K(+) ratio was elevated during the fresh water phase and subsequently decreased upon return to salt water. Aldosterone and corticosterone were not altered during exposure to fresh water. Elevated water flux rates during fresh water exposure reflected an increase in water consumption, resulting in a decrease in ionic and osmotic concentrations. The lack of a change in adrenocorticoids to acute fresh water exposure suggests that adrenal responsiveness to an hypo-osmotic environment may be delayed in marine turtles when compared to marine mammals.

  19. Private Information and Insurance Rejections

    PubMed Central

    Hendren, Nathaniel

    2013-01-01

    Across a wide set of non-group insurance markets, applicants are rejected based on observable, often high-risk, characteristics. This paper argues that private information, held by the potential applicant pool, explains rejections. I formulate this argument by developing and testing a model in which agents may have private information about their risk. I first derive a new no-trade result that theoretically explains how private information could cause rejections. I then develop a new empirical methodology to test whether this no-trade condition can explain rejections. The methodology uses subjective probability elicitations as noisy measures of agents beliefs. I apply this approach to three non-group markets: long-term care, disability, and life insurance. Consistent with the predictions of the theory, in all three settings I find significant amounts of private information held by those who would be rejected; I find generally more private information for those who would be rejected relative to those who can purchase insurance; and I show it is enough private information to explain a complete absence of trade for those who would be rejected. The results suggest private information prevents the existence of large segments of these three major insurance markets. PMID:24187381

  20. The influence of acute unloading on left ventricular strain and strain rate by speckle tracking echocardiography in a porcine model.

    PubMed

    Dahle, Geir Olav; Stangeland, Lodve; Moen, Christian Arvei; Salminen, Pirjo-Riitta; Haaverstad, Rune; Matre, Knut; Grong, Ketil

    2016-05-15

    Noninvasive measurements of myocardial strain and strain rate by speckle tracking echocardiography correlate to cardiac contractile state but also to load, which may weaken their value as indices of inotropy. In a porcine model, we investigated the influence of acute dynamic preload reductions on left ventricular strain and strain rate and their relation to the pressure-conductance catheter-derived preload recruitable stroke work (PRSW) and peak positive first derivative of left ventricular pressure (LV-dP/dtmax). Speckle tracking strain and strain rate in the longitudinal, circumferential, and radial directions were measured during acute dynamic reductions of end-diastolic volume during three different myocardial inotropic states. Both strain and strain rate were sensitive to unloading of the left ventricle (P < 0.001), but the load dependency for strain rate was modest compared with strain. Changes in longitudinal and circumferential strain correlated more strongly to changes in end-diastolic volume (r = -0.86 and r = -0.72) than did radial strain (r = 0.35). Longitudinal, circumferential, and radial strain significantly correlated with LV-dP/dtmax (r = -0.53, r = -0.46, and r = 0.86), whereas only radial strain correlated with PRSW (r = 0.55). Strain rate in the longitudinal, circumferential and radial direction significantly correlated with both PRSW (r = -0.64, r = -0.58, and r = 0.74) and LV-dP/dtmax (r = -0.95, r = -0.70, and r = 0.85). In conclusion, the speckle tracking echocardiography-derived strain rate is more robust to dynamic ventricular unloading than strain. Longitudinal and circumferential strain could not predict load-independent contractility. Strain rates, and especially in the radial direction, are good predictors of preload-independent inotropic markers derived from conductance catheter. PMID:26968547

  1. Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

    PubMed

    Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

    2015-01-01

    Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation. PMID:26335204

  2. Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection

    PubMed Central

    Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

    2015-01-01

    Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation. PMID:26335204

  3. Space vehicle thermal rejection system

    NASA Technical Reports Server (NTRS)

    Tanzer, Herbert J. (Inventor)

    1989-01-01

    A space vehicle thermal heat rejection system 10 utilizing separate optimized heat pipe components for the functions of heat acquisition, heat transport, and heat rejection. A honeycomb panel heat pipe evaporator section 20 performs the function of heat acquisition, and forms a closed thermodynamic system with a dual channel heat pipe transport section 30, which performs the function of heat transport. A plurality of truss or channel core heat pipe rejection fins 41 form the condenser section 40, which performs the function of heat rejection. A common wall 32 separates the condenser section 40 from the transport section 30. Using the above heat pipe components and having efficient interfacing between them results in high performance factors for the overall system.

  4. Acute and Session Ratings of Perceived Exertion in a Physical Education Setting.

    PubMed

    Lagally, Kristen M; Walker-Smith, Kimberly; Henninger, Mary L; Williams, Skip M; Coleman, Margo

    2016-02-01

    A commonly stated rationale for examining the use of ratings of perceived exertion with youth is its potential value as an assessment of intensity in physical education settings. The purpose of this study was to examine the relation between ratings of perceived exertion and heart rate in a natural physical education setting. Sixth through eighth grade students performed cardiovascular and muscle endurance circuits and then recorded ratings and heart rate. It was hypothesized that, similar to laboratory studies, strong positive correlations would be seen between heart rate and ratings of perceived exertion, which would provide additional support for the use of ratings of perceived exertion in physical education. However, only low to moderate correlations were found. When data collection occurs in a natural physical education setting, there are challenges that may result in poor correlational results between variables such as heart rate and perceived exertion that demonstrate strong relationships when examined in laboratory settings. PMID:27420307

  5. Membrane rejection of nitrogen compounds

    NASA Technical Reports Server (NTRS)

    Lee, S.; Lueptow, R. M.

    2001-01-01

    Rejection characteristics of nitrogen compounds were examined for reverse osmosis, nanofiltration, and low-pressure reverse osmosis membranes. The rejection of nitrogen compounds is explained by integrating experimental results with calculations using the extended Nernst-Planck model coupled with a steric hindrance model. The molecular weight and chemical structure of nitrogen compounds appear to be less important in determining rejection than electrostatic properties. The rejection is greatest when the Donnan potential exceeds 0.05 V or when the ratio of the solute radius to the pore radius is greater than 0.8. The transport of solute in the pore is dominated by diffusion, although convective transport is significant for organic nitrogen compounds. Electromigration contributes negligibly to the overall solute transport in the membrane. Urea, a small organic compound, has lower rejection than ionic compounds such as ammonium, nitrate, and nitrite, indicating the critical role of electrostatic interaction in rejection. This suggests that better treatment efficiency for organic nitrogen compounds can be obtained after ammonification of urea.

  6. Proteomics for rejection diagnosis in renal transplant patients: Where are we now?

    PubMed Central

    Gwinner, Wilfried; Metzger, Jochen; Husi, Holger; Marx, David

    2016-01-01

    Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic. PMID:27011903

  7. Proteomics for rejection diagnosis in renal transplant patients: Where are we now?

    PubMed

    Gwinner, Wilfried; Metzger, Jochen; Husi, Holger; Marx, David

    2016-03-24

    Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic. PMID:27011903

  8. Universal noninvasive detection of solid organ transplant rejection

    PubMed Central

    Snyder, Thomas M.; Khush, Kiran K.; Valantine, Hannah A.; Quake, Stephen R.

    2011-01-01

    It is challenging to monitor the health of transplanted organs, particularly with respect to rejection by the host immune system. Because transplanted organs have genomes that are distinct from the recipient's genome, we used high throughput shotgun sequencing to develop a universal noninvasive approach to monitoring organ health. We analyzed cell-free DNA circulating in the blood of heart transplant recipients and observed significantly increased levels of cell-free DNA from the donor genome at times when an endomyocardial biopsy independently established the presence of acute cellular rejection in these heart transplant recipients. Our results demonstrate that cell-free DNA can be used to detect an organ-specific signature that correlates with rejection, and this measurement can be made on any combination of donor and recipient. This noninvasive test holds promise for replacing the endomyocardial biopsy in heart transplant recipients and may be applicable to other solid organ transplants. PMID:21444804

  9. Effect of Acute Mental Stress on Heart Rate and QT Variability in Postmyocardial Infarction Patients

    PubMed Central

    Magrì, Damiano; Piccirillo, Gianfranco; Quaglione, Raffaele; Dell'Armi, Annalaura; Mitra, Marilena; Velitti, Stefania; Di Barba, Daniele; Lizio, Andrea; Maisto, Damiana; Barillà, Francesco

    2012-01-01

    Emotionally charged events are associated with an increased risk of sudden cardiac death (SCD). In this study we assessed RR and QT variability index (QTVI) at baseline during anger recall test (AR). We calculated QTVI from a 5-min ECG recording and from a 10-beats segment around the presumed maximum sympathetic activation in thirty post-myocardial infarction patients under β-blocker therapy and 10 controls underwent. In all groups, the low-frequency component of RR and SBP increased during AR. In all recordings, the QTVI calculated on a 5-min ECG recording and the QTVI10 beats were higher in patients than in controls (P < 0.05). The QTVI during AR remained unchanged from baseline within each group. Conversely, during AR, the QTVI10 beats in controls diminished significantly (P < 0.05) from baseline whereas in patients remained unchanged. The inability to buffer an acute stress-induced increase in sympathetic activity could explain why events charged with acute stress are associated with an increased risk of ventricular arrhythmias in this setting of patients and support the role of cognitive behavior stress management strategies. PMID:22844616

  10. Diagnosis of Rejection by Analyzing Ventricular Late Potentials in Heart Transplant Patients

    PubMed Central

    Mendes, Vítor Nogueira; Pereira, Telmo Santos; Matos, Vítor Azevedo

    2016-01-01

    Background Heart transplant rejection originates slow and fragmented conduction. Signal-averaged ECG (SAECG) is a stratification method in the risk of rejection. Objective To develop a risk score for rejection, using SAECG variables. Methods We studied 28 transplant patients. First, we divided the sample into two groups based on the occurrence of acute rejection (5 with rejection and 23 without). In a second phase, we divided the sample considering the existence or not of rejection in at least one biopsy performed on the follow-up period (rejection pm1: 18 with rejection and 10 without). Results On conventional ECG, the presence of fibrosis was the only criterion associated with acute rejection (OR = 19; 95% CI = 1.65-218.47; p = 0.02). Considering the rejection pm1, an association was found with the SAECG variables, mainly with RMS40 (OR = 0.97; 95% CI = 0.87-0.99; p = 0.03) and LAS40 (OR = 1.06; 95% IC = 1.01-1.11; p = 0.03). We formulated a risk score including those variables, and evaluated its discriminative performance in our sample. The presence of fibrosis with increasing of LAS40 and decreasing of RMS40 showed a good ability to distinguish between patients with and without rejection (AUC = 0.82; p < 0.01), assuming a cutoff point of sensitivity = 83.3% and specificity = 60%. Conclusion The SAECG distinguished between patients with and without rejection. The usefulness of the proposed risk score must be demonstrated in larger follow-up studies. PMID:26815311

  11. Comparison of estimation methods for creating small area rates of acute myocardial infarction among Medicare beneficiaries in California.

    PubMed

    Yasaitis, Laura C; Arcaya, Mariana C; Subramanian, S V

    2015-09-01

    Creating local population health measures from administrative data would be useful for health policy and public health monitoring purposes. While a wide range of options--from simple spatial smoothers to model-based methods--for estimating such rates exists, there are relatively few side-by-side comparisons, especially not with real-world data. In this paper, we compare methods for creating local estimates of acute myocardial infarction rates from Medicare claims data. A Bayesian Monte Carlo Markov Chain estimator that incorporated spatial and local random effects performed best, followed by a method-of-moments spatial Empirical Bayes estimator. As the former is more complicated and time-consuming, spatial linear Empirical Bayes methods may represent a good alternative for non-specialist investigators. PMID:26291680

  12. Rates of synthesis of prealbumin and retinol-binding protein during acute inflammation in the rat.

    PubMed

    Felding, P; Fex, G

    1985-04-01

    The rates of synthesis of prealbumin (PA), retinol-binding protein (RBP), and other plasma proteins were measured in primary monolayer cultures of rat hepatocytes isolated from normal rats and from rats 18 h after induction of an inflammatory reaction by subcutaneous injection of croton oil. The inflammatory pattern of protein synthesis seemed to persist in the isolated hepatocytes for 1-2 days. This pattern included significantly decreased rates of synthesis of PA. The rate of synthesis of RBP was probably also decreased, but significantly less than the rate of PA synthesis. The results support the idea that it is mainly the decreased rate of PA synthesis which is responsible for the decreased plasma concentration of PA, and its ligand RBP and retinol during inflammation. PMID:4039519

  13. MDMA DECREASES THE EFFECTS OF SIMULATED SOCIAL REJECTION

    PubMed Central

    Frye, Charles G.; Wardle, Margaret C.; Norman, Greg J.; de Wit, Harriet

    2014-01-01

    3-4-methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N = 36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called “Cyberball” during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments. PMID

  14. Heat rejection sublimator

    NASA Technical Reports Server (NTRS)

    Dingell, Charles W. (Inventor); Quintana, Clemente E. (Inventor); Le, Suy (Inventor); Clark, Michael R. (Inventor); Cloutier, Robert E. (Inventor); Hafermalz, David Scott (Inventor)

    2009-01-01

    A sublimator includes a sublimation plate having a thermal element disposed adjacent to a feed water channel and a control point disposed between at least a portion of the thermal element and a large pore substrate. The control point includes a sintered metal material. A method of dissipating heat using a sublimator includes a sublimation plate having a thermal element and a control point. The thermal element is disposed adjacent to a feed water channel and the control point is disposed between at least a portion of the thermal element and a large pore substrate. The method includes controlling a flow rate of feed water to the large pore substrate at the control point and supplying heated coolant to the thermal element. Sublimation occurs in the large pore substrate and the controlling of the flow rate of feed water is independent of time. A sublimator includes a sublimation plate having a thermal element disposed adjacent to a feed water channel and a control point disposed between at least a portion of the thermal element and a large pore substrate. The control point restricts a flow rate of feed water from the feed water channel to the large pore substrate independent of time.

  15. Perturbations in the Urinary Exosome in Transplant Rejection

    SciTech Connect

    Sigdel, Tara K.; NG, Yolanda; Lee, Sangho; Nicora, Carrie D.; Qian, Weijun; Smith, Richard D.; Camp, David G.; Sarwal, Minnie M.

    2015-01-05

    Background: Urine exosomes, vesicles exocytosed into urine by all renal epithelial cell types, occur under normal physiologic and disease states. Exosome contents may mirror disease-specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed and for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Methods: Urine exosomes were isolated by centrifugal filtration from mid-stream, second morning void, urine samples collected from kidney transplant recipients with and without biopsy matched acute rejection. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Uexo) underwent mass spectrometry-based quantitative proteomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR). Results: Identifications of 1018 and 349 proteins, Uw and Uexo fractions, respectively, demonstrated a 279 protein overlap between the two urinary compartments with 25%(70) of overlapping proteins unique to Uexoand represented membrane bound proteins (p=9.31e-7). Of 349 urine exosomal proteins identified in transplant patients 220 were not previously identified in the normal urine exosomal fraction. Uexo proteins (11), functioning in the inflammatory / stress response, were more abundant in patients with biopsy-confirmed acute rejection, 3 of which were exclusive to Uexo. Uexo AR-specific biomarkers (8) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. Conclusions: A rapid urinary exosome isolation method and quantitative measurement of enriched Uexo proteins was applied. Urine proteins specific to the exosomal fraction were detected either in unfractionated urine (at low abundances) or by Uexo fraction analysis. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were

  16. Computed radionuclide urogram for assessing acute renal failure

    SciTech Connect

    Schlegel, J.U.; Lang, E.K.

    1980-05-01

    The computed radionuclide urogram is advocated as a noninvasive diagnostic method for differentiation of the most common prerenal, renal, and postrenal causes of acute renal failure. On the basis of characteristic changes in the effective renal plasma flow rate, the calculated filtration fraction, and the calculated glomerular filtration rate, prerenal conditions such as renal artery stenosis or thrombosis, renal conditions such as acute rejection or acute tubular necrosis, and postrenal conditions such as obstruction or leakage, which are the most common causes of acute renal failure, can be differentiated. In conjunction with morphologic criteria derived from sonograms, a diagnosis with acceptable confidence can be rendered in most instances. Both the computed radionuclide urogram and sonogram are noninvasive and can be used without adverse effects in the presence of azotemia and even anuria. This also makes feasible reexamination at intervals to assess effect of therapy and offer prognostic information.

  17. Prognostic value of left ventricular diastolic function and association with heart rate variability after a first acute myocardial infarction

    PubMed Central

    Poulsen, S; Jensen, S; Moller, J; Egstrup, K

    2001-01-01

    OBJECTIVE—To study the prognostic value of left ventricular (LV) diastolic function and its relation with autonomic balance expressed by heart rate variability (HRV) in patients after a first acute myocardial infarction.
DESIGN—The study population consisted of 64 consecutive patients with first acute myocardial infarction and 31 control subjects. Long and short term HRV indices were evaluated by 24 hour Holter monitoring, and LV systolic and diastolic function were assessed by two dimensional and Doppler echocardiography before discharge. Patients were divided into two groups: those with restrictive LV filling characteristics (deceleration time ⩽ 140 ms) and those with non-restrictive LV filling characteristics (deceleration time > 140 ms).
RESULTS—Both long and short term HRV indices were significantly reduced in patients with restrictive LV filling compared with the non-restrictive group and control subjects. Mitral deceleration time and isovolumetric relaxation time correlated weakly but significantly with all indices of HRV whereas ejection fraction correlated weakly with the long term HRV indices. The mean follow up time was 14.9 (8.7) months. Multivariate analysis showed that mitral deceleration time (χ2 = 6.4, p < 0.001) and ejection fraction ⩽ 40% (χ2 = 4.4, p < 0.05) were independent predictors of cardiac death and readmission to hospital with congestive heart failure.
CONCLUSIONS—A restrictive LV filling pattern was found to be the strongest predictor of adverse outcome independent of HRV and ejection fraction during follow up after a first acute myocardial infarction. Patients with restrictive LV filling characteristics had more reduced HRV than those with non-restrictive diastolic filling.


Keywords: diastole; infarction; autonomic balance PMID:11559672

  18. The severity of shock is associated with impaired rates of net alveolar fluid clearance in clinical acute lung injury.

    PubMed

    Zeyed, Yosaf F; Bastarache, Julie A; Matthay, Michael A; Ware, Lorraine B

    2012-09-15

    The rate of alveolar fluid clearance (AFC) is associated with mortality in clinical acute lung injury (ALI). Patients with ALI often develop circulatory shock, but how shock affects the rate of AFC is unknown. To determine the effect of circulatory shock on the rate of AFC in patients with ALI, the rate of net AFC was measured in 116 patients with ALI by serial sampling of pulmonary edema fluid. The primary outcome was the rate of AFC in patients with shock compared with those without shock. We also tested the effects of shock severity and bacteremia. Patients with ALI and shock (n = 86) had significantly slower rates of net AFC compared with those without shock (n = 30, P = 0.03), and AFC decreased significantly as the number of vasopressors increased. Patients with positive blood cultures (n = 21) had slower AFC compared with patients with negative blood cultures (n = 96, P = 0.023). In addition, the edema fluid-to-plasma protein ratio, an index of alveolar-capillary barrier permeability, was highest in patients requiring the most vasopressors (P < 0.05). Patients with ALI complicated by circulatory shock and bacteremia had slower rates of AFC compared with patients without shock or bacteremia. An impaired capacity to reabsorb alveolar edema fluid may contribute to high mortality among patients with sepsis-induced ALI. These findings also suggest that vasopressor use may be a marker of alveolar-capillary barrier permeability in ALI and provide justification for new therapies that enhance alveolar epithelial and endothelial barrier integrity in ALI, particularly in patients with shock. PMID:22821995

  19. Changes in heart rate variability associated with acute alcohol consumption: current knowledge and implications for practice and research.

    PubMed

    Romanowicz, Magdalena; Schmidt, John E; Bostwick, John M; Mrazek, David A; Karpyak, Victor M

    2011-06-01

    Alcohol consumption is associated with a broad array of physiologic and behavioral effects including changes in heart rate. However, the physiologic mechanisms of alcohol effects and the reasons for individual differences in the cardiac response remain unknown. Measuring changes in resting heart rate (measured as beats/min) has not been found to be as sensitive to alcohol's effects as changes in heart rate variability (HRV). HRV is defined as fluctuations in interbeat interval length which reflect the heart's response to extracardiac factors that affect heart rate. HRV allows simultaneous assessment of both sympathetic and parasympathetic activity and the interplay between them. Increased HRV has been associated with exercise and aerobic fitness, while decreased HRV has been associated with aging, chronic stress, and a wide variety of medical and psychiatric disorders. Decreased HRV has predictive value for mortality in general population samples and patients with myocardial infarction and used as an indicator of altered autonomic function. A significant inverse correlation was found between HRV and both the severity of depression and the duration of the depressive episode. HRV analysis provides insights into mechanisms of autonomic regulation and is extensively used to clarify relationships between depression and cardiovascular disease. This article will review the methodology of HRV measurements and contemporary knowledge about effects of acute alcohol consumption on HRV. Potential implications of this research include HRV response to alcohol that could serve as a marker for susceptibility to alcoholism. At present however there is almost no research data supporting this hypothesis. PMID:21332532

  20. Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia

    SciTech Connect

    Komatsu, K.; Takada, G.; Uemura, K.; Shishido, F.; Kanno, I. )

    1990-09-01

    We measured changes in the regional cerebral metabolic rate of glucose (rCMRGlu) using {sup 18}F-fluorodeoxyglucose and positron emission tomography for the assessment of neurotoxicity in childhood acute lymphocytic leukemia treated with high-dose methotrexate (HD-MTX) therapy. We studied 8 children with acute lymphocytic leukemia (mean age: 9.6 years) treated with HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. CMRGlu after HD-MTX therapy was most reduced (40%) in the patient who had central nervous system leukemia and was treated with the largest total doses of both intrathecal MTX (IT-MTX) and HD-MTX. CMRGlu in the whole brain after HD-MTX therapy was reduced by an average of 21% (P less than 0.05). The reductions of CMRGlu in 8 patients were correlated with total doses of both IT-MTX (r = 0.717; P less than 0.05) and systemic HD-MTX (r = 0.784; P less than 0.05). CMRGlu of the cerebral cortex, especially the frontal and occipital cortex, was reduced more noticeably than that of the basal ganglia and white matter. We suggest that the measurement of changes in rCMRGlu after HD-MTX therapy is useful for detecting accumulated MTX neurotoxicity.

  1. Modulation of heart rate response to acute stressors throughout the breeding season in the king penguin Aptenodytes patagonicus.

    PubMed

    Viblanc, Vincent A; Smith, Andrew D; Gineste, Benoit; Kauffmann, Marion; Groscolas, René

    2015-06-01

    'Fight-or-flight' stress responses allow animals to cope adaptively to sudden threats by mobilizing energy resources and priming the body for action. Because such responses can be costly and redirect behavior and energy from reproduction to survival, they are likely to be shaped by specific life-history stages, depending on the available energy resources and the commitment to reproduction. Here, we consider how heart rate (HR) responses to acute stressors are affected by the advancing breeding season in a colonial seabird, the king penguin (Aptenodytes patagonicus). We subjected 77 birds (44 males, 33 females) at various stages of incubation and chick-rearing to three experimental stressors (metal sound, distant approach and capture) known to vary both in their intensity and associated risk, and monitored their HR responses. Our results show that HR increase in response to acute stressors was progressively attenuated with the stage of breeding from incubation to chick-rearing. Stress responses did not vary according to nutritional status or seasonal timing (whether breeding was initiated early or late in the season), but were markedly lower during chick-rearing than during incubation. This pattern was obvious for all three stressors. We discuss how 'fight-or-flight' responses may be modulated by considering the energy commitment to breeding, nutritional status and reproductive value of the brood in breeding seabirds. PMID:25883375

  2. Acute stress in pregnant rats: effects on growth rate, learning, and memory capabilities of the offspring.

    PubMed

    Lordi, B; Protais, P; Mellier, D; Caston, J

    1997-11-01

    Growth rate of the offspring of female rats stressed by the presence of a cat at the 10th or the 19th gestational day was lower than that of controls whereas footshocks administered at the same periods did not significantly influence growth rate of the young. Whatever the nature of the stress and the time when it was administered to the mother, the death rate of the young rats was much greater than that in controls. When adult, the offspring of stressed mothers exhibited learning and memory impairments in a delayed alternation task as well as in passive avoidance conditioning. Alteration of these cognitive functions is interpreted in terms of subtle dysfunctions in the development of the nervous system through modifications of the hormonal components of the mothers, particularly eventual alterations of the nervous system biochemistry of the offspring. PMID:9333204

  3. Impact of resuscitation and thrombolysis on mortality rate from acute myocardial infarction.

    PubMed

    Trent, R; Adams, J; Jennings, K; Rawles, J

    1995-03-24

    Our objective was to estimate the saving of life by thrombolysis and resuscitation in acute myocardial infarction (AMI) before and after hospital admission. We studied all 1516 patients admitted to a Scottish teaching hospital in 1990 and 1992 who had a final diagnosis of AMI, and 311 patients enrolled in the Grampian region early anistreplase trial (GREAT). Cardiac arrest occurred in 250/1516 (16%) hospital patients. Of these, 77 (31%) were discharged alive--a saving of 51 lives per thousand cases. 797 (53%) patients received thrombolysis, of whom 114 (14%) died. Assuming the same relative reduction in mortality as in the second international study of infarct survival (ISIS-2; 23%), 34 lives were saved by thrombolytic therapy, representing 22 lives per thousand cases. Of 311 patients in GREAT, 15 (5%) had prehospital cardiac arrest, with 7 patients surviving to discharge (48%)--a saving of 23 lives per thousand cases. Those patients given domiciliary thrombolysis had a one month mortality of 6.7% (11/163) compared with 12.2% (18/148) for those receiving hospital thrombolysis--a saving of 55 lives per thousand cases for prehospital thrombolysis. This is additional to 28 lives per thousand estimated for thrombolytic therapy in hospital, totalling 83 lives saved per thousand cases of AMI receiving thrombolytic therapy prehospital. In hospital, more lives were saved by resuscitation than by thrombolytic therapy, but this ratio was reversed in the period before hospital admission. These results emphasise the paramount importance of resuscitation in hospital, and the enhanced efficacy of thrombolysis when given at the earliest opportunity. PMID:7607764

  4. Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation.

    PubMed

    Ballen, Karen; Woo Ahn, Kwang; Chen, Min; Abdel-Azim, Hisham; Ahmed, Ibrahim; Aljurf, Mahmoud; Antin, Joseph; Bhatt, Ami S; Boeckh, Michael; Chen, George; Dandoy, Christopher; George, Biju; Laughlin, Mary J; Lazarus, Hillard M; MacMillan, Margaret L; Margolis, David A; Marks, David I; Norkin, Maxim; Rosenthal, Joseph; Saad, Ayman; Savani, Bipin; Schouten, Harry C; Storek, Jan; Szabolcs, Paul; Ustun, Celalettin; Verneris, Michael R; Waller, Edmund K; Weisdorf, Daniel J; Williams, Kirsten M; Wingard, John R; Wirk, Baldeep; Wolfs, Tom; Young, Jo-Anne H; Auletta, Jeffrey; Komanduri, Krishna V; Lindemans, Caroline; Riches, Marcie L

    2016-09-01

    Alternative graft sources (umbilical cord blood [UCB], matched unrelated donors [MUD], or mismatched unrelated donors [MMUD]) enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcomes among different graft sources. However, the risk and types of infections have not been compared among graft sources. Such information may influence the choice of a particular graft source. We compared the incidence of bacterial, viral, and fungal infections in 1781 adults with acute leukemia who received alternative donor HCT (UCB, n= 568; MUD, n = 930; MMUD, n = 283) between 2008 and 2011. The incidences of bacterial infection at 1 year were 72%, 59%, and 65% (P < .0001) for UCB, MUD, and MMUD, respectively. Incidences of viral infection at 1 year were 68%, 45%, and 53% (P < .0001) for UCB, MUD, and MMUD, respectively. In multivariable analysis, bacterial, fungal, and viral infections were more common after either UCB or MMUD than after MUD (P < .0001). Bacterial and viral but not fungal infections were more common after UCB than MMUD (P = .0009 and <.0001, respectively). The presence of viral infection was not associated with an increased mortality. Overall survival (OS) was comparable among UCB and MMUD patients with Karnofsky performance status (KPS) ≥ 90% but was inferior for UCB for patients with KPS < 90%. Bacterial and fungal infections were associated with poorer OS. Future strategies focusing on infection prevention and treatment are indicated to improve HCT outcomes. PMID:27343716

  5. Augmented orbiter heat rejection study

    NASA Technical Reports Server (NTRS)

    Hixon, C. W.

    1981-01-01

    Spacecraft radiator concepts are presented that relieve attitude restrictions required by the shuttle orbiter space radiator for baseline and extended capability STS missions. Cost effective heat rejection kits are considered which add additional capability in the form of attached spacelab radiators or a deployable radiator module.

  6. Automated Non-invasive Video-Microscopy of Oyster Spat Heart Rate during Acute Temperature Change: Impact of Acclimation Temperature

    PubMed Central

    Domnik, Nicolle J.; Polymeropoulos, Elias T.; Elliott, Nicholas G.; Frappell, Peter B.; Fisher, John T.

    2016-01-01

    We developed an automated, non-invasive method to detect real-time cardiac contraction in post-larval (1.1–1.7 mm length), juvenile oysters (i.e., oyster spat) via a fiber-optic trans-illumination system. The system is housed within a temperature-controlled chamber and video microscopy imaging of the heart was coupled with video edge-detection to measure cardiac contraction, inter-beat interval, and heart rate (HR). We used the method to address the hypothesis that cool acclimation (10°C vs. 22°C—Ta10 or Ta22, respectively; each n = 8) would preserve cardiac phenotype (assessed via HR variability, HRV analysis and maintained cardiac activity) during acute temperature changes. The temperature ramp (TR) protocol comprised 2°C steps (10 min/experimental temperature, Texp) from 22°C to 10°C to 22°C. HR was related to Texp in both acclimation groups. Spat became asystolic at low temperatures, particularly Ta22 spat (Ta22: 8/8 vs. Ta10: 3/8 asystolic at Texp = 10°C). The rate of HR decrease during cooling was less in Ta10 vs. Ta22 spat when asystole was included in analysis (P = 0.026). Time-domain HRV was inversely related to temperature and elevated in Ta10 vs. Ta22 spat (P < 0.001), whereas a lack of defined peaks in spectral density precluded frequency-domain analysis. Application of the method during an acute cooling challenge revealed that cool temperature acclimation preserved active cardiac contraction in oyster spat and increased time-domain HRV responses, whereas warm acclimation enhanced asystole. These physiologic changes highlight the need for studies of mechanisms, and have translational potential for oyster aquaculture practices. PMID:27445833

  7. Automated Non-invasive Video-Microscopy of Oyster Spat Heart Rate during Acute Temperature Change: Impact of Acclimation Temperature.

    PubMed

    Domnik, Nicolle J; Polymeropoulos, Elias T; Elliott, Nicholas G; Frappell, Peter B; Fisher, John T

    2016-01-01

    We developed an automated, non-invasive method to detect real-time cardiac contraction in post-larval (1.1-1.7 mm length), juvenile oysters (i.e., oyster spat) via a fiber-optic trans-illumination system. The system is housed within a temperature-controlled chamber and video microscopy imaging of the heart was coupled with video edge-detection to measure cardiac contraction, inter-beat interval, and heart rate (HR). We used the method to address the hypothesis that cool acclimation (10°C vs. 22°C-Ta10 or Ta22, respectively; each n = 8) would preserve cardiac phenotype (assessed via HR variability, HRV analysis and maintained cardiac activity) during acute temperature changes. The temperature ramp (TR) protocol comprised 2°C steps (10 min/experimental temperature, Texp) from 22°C to 10°C to 22°C. HR was related to Texp in both acclimation groups. Spat became asystolic at low temperatures, particularly Ta22 spat (Ta22: 8/8 vs. Ta10: 3/8 asystolic at Texp = 10°C). The rate of HR decrease during cooling was less in Ta10 vs. Ta22 spat when asystole was included in analysis (P = 0.026). Time-domain HRV was inversely related to temperature and elevated in Ta10 vs. Ta22 spat (P < 0.001), whereas a lack of defined peaks in spectral density precluded frequency-domain analysis. Application of the method during an acute cooling challenge revealed that cool temperature acclimation preserved active cardiac contraction in oyster spat and increased time-domain HRV responses, whereas warm acclimation enhanced asystole. These physiologic changes highlight the need for studies of mechanisms, and have translational potential for oyster aquaculture practices. PMID:27445833

  8. Recanalization and Mortality Rates of Thrombectomy With Stent-Retrievers in Octogenarian Patients with Acute Ischemic Stroke

    SciTech Connect

    Parrilla, G.; Carreón, E.; Zamarro, J.; Espinosa de Rueda, M.; García-Villalba, B.; Marín, F.; Hernández-Fernández, F.; Morales, A.; Fernández-Vivas, M.; Núñez, R.; Moreno, A.

    2015-04-15

    BackgroundOur objective was to evaluate the effect of treatment with stent-retrievers in octogenarians suffering an acute ischemic stroke.MethodsA total of 150 consecutive patients with acute stroke who were treated with stent-retrievers between April 2010 and June 2012 were retrospectively reviewed. Patients were divided into those <80 years old (n = 116) and those ≥80 (n = 34). Baseline characteristics, procedure data, and endpoints (postprocedural NIHSS, death, and mRS at 3 months) were compared.ResultsHigh blood pressure, atrial fibrillation, and anticoagulation were more frequent in octogenarians (p = 0.01, 0.003, and 0.04 respectively). There were no differences between both groups regarding previous intravenous thrombolysis (32.4 vs. 48.3 %, p = 0.1), preprocedural NIHSS (18.1 vs. 16.8, p = 0.3), procedure time (74.5 (40–114) min vs. 63 (38–92) min, p = 0.2), revascularization time (380.5 (298–526.3) min vs. 350 (296.3–452.8), p = 0.3), TICI ≥ 2B (88.2 vs. 93.9 %, p = 0.1), and symptomatic haemorrhage (5.9 vs. 2.6 %, p = 0.3). Discharge NIHSS was higher in octogenarians (9.7 vs. 6.5, p = 0.03). Death and 3-month mRS ≥3 were more frequent in octogenarians (35.3 vs. 17.2 %, p = 0.02 and 73.5 vs. 37.1 %, p = 0.02). ICA-involvement and prolonged revascularization involved higher mortality (66.7 vs. 27.6 %, p = 0.03) and worse mRS (50 vs. 24.4 %, p = 0.06) in octogenarians.ConclusionsIn our series, treatment with stent-retrievers in octogenarians with acute ischemic stroke achieved good rates of recanalization but with a high mortality rate. ICA involvement and revascularization times beyond 6 hours associated to a worse prognosis. These data might be of value in the design of prospective studies evaluating the clinical efficacy of the endovascular treatments in octogenarians.

  9. Does amifostine reduce metabolic rate? Effect of the drug on gas exchange and acute ventilatory hypoxic response in humans.

    PubMed

    Pandit, Jaideep J; Allen, Caroline; Little, Evelyn; Formenti, Federico; Harris, Adrian L; Robbins, Peter A

    2015-01-01

    Amifostine is added to chemoradiation regimens in the treatment of many cancers on the basis that, by reducing the metabolic rate, it protects normal cells from toxic effects of therapy. We tested this hypothesis by measuring the metabolic rate (by gas exchange) over 255 min in 6 healthy subjects, at two doses (500 mg and 1000 mg) of amifostine infused over 15 min at the start of the protocol. We also assessed the ventilatory response to six 1 min exposures to isocapnic hypoxia mid-protocol. There was no change in metabolic rate with amifostine as measured by oxygen uptake (p = 0.113). However in carbon dioxide output and respiratory quotient, we detected a small decline over time in control and drug protocols, consistent with a gradual change from carbohydrate to fat metabolism over the course of the relatively long study protocol. A novel result was that amifostine (1000 mg) increased the mean ± SD acute hypoxic ventilatory response from 12.4 ± 5.1 L/min to 20.3 ± 11.9 L/min (p = 0.045). In conclusion, any cellular protective effects of amifostine are unlikely due to metabolic effects. The stimulatory effect on hypoxic ventilatory responses may be due to increased levels of hypoxia inducible factor, either peripherally in the carotid body, or centrally in the brain. PMID:25894815

  10. Greater Heart Rate Responses to Acute Stress Are Associated with Better Post-Error Adjustment in Special Police Cadets.

    PubMed

    Yao, Zhuxi; Yuan, Yi; Buchanan, Tony W; Zhang, Kan; Zhang, Liang; Wu, Jianhui

    2016-01-01

    High-stress jobs require both appropriate physiological regulation and behavioral adjustment to meet the demands of emergencies. Here, we investigated the relationship between the autonomic stress response and behavioral adjustment after errors in special police cadets. Sixty-eight healthy male special police cadets were randomly assigned to perform a first-time walk on an aerial rope bridge to induce stress responses or a walk on a cushion on the ground serving as a control condition. Subsequently, the participants completed a Go/No-go task to assess behavioral adjustment after false alarm responses. Heart rate measurements and subjective reports confirmed that stress responses were successfully elicited by the aerial rope bridge task in the stress group. In addition, greater heart rate increases during the rope bridge task were positively correlated with post-error slowing and had a trend of negative correlation with post-error miss rate increase in the subsequent Go/No-go task. These results suggested that stronger autonomic stress responses are related to better post-error adjustment under acute stress in this highly selected population and demonstrate that, under certain conditions, individuals with high-stress jobs might show cognitive benefits from a stronger physiological stress response. PMID:27428280

  11. The acute effects of daily nicotine intake on heart rate--a toxicokinetic and toxicodynamic modelling study.

    PubMed

    Gajewska, M; Worth, A; Urani, C; Briesen, H; Schramm, K-W

    2014-10-01

    Joint physiologically-based toxicokinetic and toxicodynamic (PBTK/TD) modelling was applied to simulate concentration-time profiles of nicotine, a well-known stimulant, in the human body following single and repeated dosing. Both kinetic and dynamic models were first calibrated by using in vivo literature data for the Caucasian population. The models were then used to estimate the blood and liver concentrations of nicotine in terms of the Area Under Curve (AUC) and the peak concentration (Cmax) for selected exposure scenarios based on inhalation (cigarette smoking), oral intake (nicotine lozenges) and dermal absorption (nicotine patches). The model simulations indicated that whereas frequent cigarette smoking gives rise to high AUC and Cmax in blood, the use of nicotine-rich dermal patches leads to high AUC and Cmax in the liver. Venous blood concentrations were used to estimate one of the most common acute effects, mean heart rate, both at rest and during exercise. These estimations showed that cigarette smoking causes a high peak heart rate, whereas dermal absorption causes a high mean heart rate over 48h. This study illustrates the potential of using PBTK/TD modelling in the safety assessment of nicotine-containing products. PMID:25066669

  12. A fluid response: Alpha-amylase reactions to acute laboratory stress are related to sample timing and saliva flow rate.

    PubMed

    Nagy, Tamás; van Lien, René; Willemsen, Gonneke; Proctor, Gordon; Efting, Marieke; Fülöp, Márta; Bárdos, György; Veerman, Enno C I; Bosch, Jos A

    2015-07-01

    Salivary alpha-amylase (sAA) is used as a sympathetic (SNS) stress marker, though its release is likely co-determined by SNS and parasympathetic (PNS) activation. The SNS and PNS show asynchronous changes during acute stressors, and sAA responses may thus vary with sample timing. Thirty-four participants underwent an eight-minute memory task (MT) and cold pressor task (CPT). Cardiovascular SNS (pre-ejection period, blood pressure) and PNS (heart rate variability) activity were monitored continuously. Unstimulated saliva was collected repeatedly during and after each laboratory stressor, and sAA concentration (U/ml) and secretion (U/minute) determined. Both stressors increased anxiety. The MT caused an immediate and continued cardiac SNS activation, but sAA concentration increased at task cessation only (+54%); i.e., when there was SNS-PNS co-activation. During the MT sAA secretion even decreased (-35%) in conjunction with flow rate and vagal tone. The CPT robustly increased blood pressure but not sAA. In summary, sAA fluctuations did not parallel changes in cardiac SNS activity or anxiety. sAA responses seem contingent on sample timing and flow rate, likely involving both SNS and PNS influences. Verification using other stressors and contexts seems warranted. PMID:25976524

  13. Greater Heart Rate Responses to Acute Stress Are Associated with Better Post-Error Adjustment in Special Police Cadets

    PubMed Central

    Yao, Zhuxi; Yuan, Yi; Buchanan, Tony W.; Zhang, Kan; Zhang, Liang; Wu, Jianhui

    2016-01-01

    High-stress jobs require both appropriate physiological regulation and behavioral adjustment to meet the demands of emergencies. Here, we investigated the relationship between the autonomic stress response and behavioral adjustment after errors in special police cadets. Sixty-eight healthy male special police cadets were randomly assigned to perform a first-time walk on an aerial rope bridge to induce stress responses or a walk on a cushion on the ground serving as a control condition. Subsequently, the participants completed a Go/No-go task to assess behavioral adjustment after false alarm responses. Heart rate measurements and subjective reports confirmed that stress responses were successfully elicited by the aerial rope bridge task in the stress group. In addition, greater heart rate increases during the rope bridge task were positively correlated with post-error slowing and had a trend of negative correlation with post-error miss rate increase in the subsequent Go/No-go task. These results suggested that stronger autonomic stress responses are related to better post-error adjustment under acute stress in this highly selected population and demonstrate that, under certain conditions, individuals with high-stress jobs might show cognitive benefits from a stronger physiological stress response. PMID:27428280

  14. The private rejection of unfair offers and emotional commitment.

    PubMed

    Yamagishi, Toshio; Horita, Yutaka; Takagishi, Haruto; Shinada, Mizuho; Tanida, Shigehito; Cook, Karen S

    2009-07-14

    In a series of experiments, we demonstrate that certain players of an economic game reject unfair offers even when this behavior increases rather than decreases inequity. A substantial proportion (30-40%, compared with 60-70% in the standard ultimatum game) of those who responded rejected unfair offers even when rejection reduced only their own earnings to 0, while not affecting the earnings of the person who proposed the unfair split (in an impunity game). Furthermore, even when the responders were not able to communicate their anger to the proposers by rejecting unfair offers in a private impunity game, a similar rate of rejection was observed. The rejection of unfair offers that increases inequity cannot be explained by the social preference for inequity aversion or reciprocity; however, it does provide support for the model of emotion as a commitment device. In this view, emotions such as anger or moral disgust lead people to disregard the immediate consequences of their behavior, committing them to behave consistently to preserve integrity and maintain a reputation over time as someone who is reliably committed to this behavior. PMID:19564602

  15. Multi-scale heart rate dynamics detected by phase-rectified signal averaging predicts mortality after acute myocardial infarction

    PubMed Central

    Kisohara, Masaya; Stein, Phyllis K.; Yoshida, Yutaka; Suzuki, Mari; Iizuka, Narushi; Carney, Robert M.; Watkins, Lana L.; Freedland, Kenneth E.; Blumenthal, James A.; Hayano, Junichiro

    2013-01-01

    Aims Acceleration and deceleration capacity (AC and DC) for beat-to-beat short-term heart rate dynamics are powerful predictors of mortality after acute myocardial infarction (AMI). We examined if AC and DC for minute-order long-term heart rate dynamics also have independent predictive value. Methods and results We studied 24-hr Holter electrcardiograms in 708 post-AMI patients who were followed up for up to 30 months thereafter. Acceleration capacity and DC was calculated with the time scales of T (window size defining heart rate) and s (wavelet scale) from 1 to 500 s and compared their prognostic values with conventional measures (ACconv and DCconv) that were calculated with (T,s) = [1,2 (beat)]. During the follow-up, 47 patients died. Both increased ACconv and decreased DCconv predicted mortality (C statistic, 0.792 and 0.797). Concordantly, sharp peaks of C statistics were observed at (T,s) = [2,7 (sec)] for both increased AC and decreased DC (0.762 and 0.768), but there were larger peaks of C statistics at around [30,60 (sec)] for both (0.783 and 0.796). The C statistic was greater for DC than AC at (30,60) (P = 0.0012). Deceleration capacity at (30,60) was a significant predictor even after adjusted for ACconv (P = 0.020) and DCconv (P = 0.028), but the predictive power of AC at (30,60) was no longer significant. Conclusion A decrease in DC for minute-order long-term heart rate dynamics is a strong predictor for post-AMI mortality and the predictive power is independent of ACconv and DCconv for beat-to-beat short-term heart rate dynamics. PMID:23248218

  16. High-strain-rate brain injury model using submerged acute rat brain tissue slices.

    PubMed

    Sarntinoranont, Malisa; Lee, Sung J; Hong, Yu; King, Michael A; Subhash, Ghatu; Kwon, Jiwoon; Moore, David F

    2012-01-20

    Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID:21970544

  17. Effect of acute exposure to ozone on heart rate and blood pressure of the conscious rat

    SciTech Connect

    Uchiyama, I.; Simomura, Y.; Yokoyama, E.

    1985-12-01

    Electrocardiogram and arterial blood pressure in conscious and unrestrained rats of various ages were recorded during a 3-hr exposure to filtered air or 1 ppm ozone (O/sub 3/). In general, heart rate and mean arterial blood pressure of rats significantly decreased during exposure to O/sub 3/, whereas these functional parameters remained almost stable during exposure to filtered air. Heart rate usually reached a plateau during the exposure to O/sub 3/. Additionally, PR interval and QRS complex significantly increased and premature atrial contraction and incomplete A-V block were frequently observed during the exposure to O/sub 3/. These circulatory effects of O/sub 3/ were more markedly manifested by rats 11 weeks old than either those 8 or 4 weeks old. On the other hand, no significant difference in the circulatory responses was observed between male and female rats. These circulatory effects of O/sub 3/ may be significant from the viewpoint of health effects, although its mechanisms remain unsolved.

  18. Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans.

    PubMed

    Seifert, John G; Nelson, Aaron; Devonish, Julia; Burke, Edmund R; Stohs, Sidney J

    2011-01-01

    Confusion and controversy exist regarding the cardiovascular effects of dietary supplements containing caffeine and Citrus aurantium (bitter orange) extract. The primary protoalkaloidal ingredient in bitter orange extract is p-synephrine which has some structural similarities to ephedrine and nor-epinephrine, but exhibits markedly different pharmacokinetic and receptor binding properties. The goal of this study was to investigate the cardiovascular effects of a product containing caffeine, bitter orange extract (p-synephrine) and green tea extract in mildly overweight individuals. Fourteen female and nine male subjects (age 24.7 ±7.4 yrs, BMI: 26.6 ±3.8) volunteered in this randomized, placebo-controlled, crossover, double-blind designed study. On day one, subjects entered the laboratory following an overnight fast. Heart rate and blood pressure were recorded at 60 min. Expired air was analyzed for the next 10 min of the session. At each of three meals, subjects ingested one capsule that was either a non-caloric placebo or a dietary supplement that contained 13 mg p-synephrine and 176 mg caffeine. On the following day, the subjects returned and repeated the protocol for data collection beginning 60 min after consuming one capsule of the placebo or the dietary supplement. No effects of the dietary supplement on heart rate, systolic and diastolic blood pressure or mean arterial pressure were observed. No between or within group differences were observed when data were analyzed for gender and caffeine usage. A small but significant decrease in resting respiratory exchange ratio was observed for the low caffeine user group in response to the product containing caffeine and p-synephrine. The results of this study indicate that ingestion of a product containing bitter orange extract, caffeine and green tea extract does not lead to increased cardiovascular stress and that fat oxidation may increase in certain populations. PMID:21448304

  19. Effect of verapamil on heart rate variability after an acute myocardial infarction. Danish Verapamil Infarction Trial II.

    PubMed

    Vaage-Nilsen, M; Rasmussen, V

    1998-07-01

    Because decreased heart rate variability measured after an acute myocardial infarction (AMI) has been demonstrated to predict subsequent mortality and sudden death, and an efficacy analysis of the Danish Verapamil Infarction Trial II (DAVIT II) demonstrated that long-term postinfarction treatment with verapamil significantly reduced sudden death, the aim of the present substudy was to evaluate the effect of verapamil on heart-rate variability in the time and frequency domain, measured in two 5-minute segments during the day and night. Thirty-eight patients were examined by Holter monitoring, at 1 week, that is, before randomization, and at 1 month after infarction; 22 of the patients were examined 12-16 months after infarction as well. In both treatment groups (verapamil and placebo) no significant alteration of heart rate variability during the day-time was demonstrated from before to after 1 and 12-16 months of treatment. In accord with the known reduction of overall heart rate by verapamil, a significant increase of mean NN interval from before to after 1 (P = 0.0004) and 12-16 months (P = 0.004) of treatment was seen in the verapamil, but not in the placebo, group at night. Parameters generally interpreted as an index of parasympathetic modulation, that is, RMSSD, pNN50, and high-frequency power, increased significantly at 1 month (P = 0.04, P = 0.03, NS, respectively) and 12-16 months (P = 0.03, P = 0.04, P < 0.05) after AMI in the verapamil, but not in the placebo, group. In conclusion, the present study indicates that verapamil shifts the autonomic balance to a vagal preponderance or sympathetic attenuation in the postinfarction period. PMID:9784908

  20. Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

    SciTech Connect

    Ganusov, Vitaly V; Korber, Bette M; Perelson, Alan S

    2009-01-01

    Human immunodeficiency virus (HIV) often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. However, the importance and quantitative details of CTL escape in humans are poorly understood. In part, this is because most studies looking at escape of HIV from CTL responses are cross-sectional and are limited to early or chronic phases of the infection. We use a novel technique of single genome amplification (SGA) to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We find that HIV escapes from virus-specific CTL responses as early as 30-50 days since the infection, and the rates of viral escapes during acute phase of the infection are much higher than was estimated in previous studies. However, even though with time virus acquires additional escape mutations, these late mutations accumulate at a slower rate. A poor correlation between the rate of CTL escape in a particular epitope and the magnitude of the epitope-specific CTL response suggests that the lower rate of late escapes is unlikely due to a low efficacy of the HIV-specific CTL responses in the chronic phase of the infection. Instead, our results suggest that late and slow escapes are likely to arise because of high fitness cost to the viral replication associated with such CTL escapes. Targeting epitopes in which virus escapes slowly or does not escape at all by CTL responses may, therefore, be a promising direction for the development of T cell based HIV vaccines.

  1. Trends of hospitalizations, fatality rate and costs for acute myocardial infarction among Spanish diabetic adults, 2001-2006

    PubMed Central

    2010-01-01

    Background Acute myocardial infarction (AMI) is one of the more frequent reasons diabetic patients are admitted to hospital, and there are reports that the long-term prognosis after an AMI is much worse in these patients than in non-diabetic patients. This study aims to compare hospital admissions and costs in Spanish diabetic and non-diabetic subjects due to AMI during the period 2001-2006. Methods We conducted a retrospective study of 6 years of national hospitalization data associated with diabetes using the Minimum Basic Data Set. National hospitalization rates were calculated for AMI among diabetic and non-diabetic adults. Fatality rates, mean hospital stay and direct medical costs related to hospitalization were analyzed. Costs were calculated using Diagnosis-Related Groups for AMI in diabetics and non-diabetics patients. Results During the study period, a total of 307,099 patients with AMI were admitted to Spanish hospitals. Diabetic patients made up 29.6% of the total. The estimated incidence due to AMI in diabetics increased from 54.7 cases per 100,000 in 2001 to 64.1 in 2006. Diabetic patients had significantly higher mortality than nondiabetic patients after adjusting for age, gender, and year (OR 1.11 [95% CI, 1.08-1.14]). The cost among diabetic patients increased by 21.3% from 2001 to 2006. Conclusions Diabetic patients have higher rates of hospital admission and fatality rates during the hospitalization after an AMI than nondiabetic patients. Diabetic adults who have suffered an AMI have a greater than expected increase in direct hospital costs over the period 2001-2006. PMID:20205960

  2. Dosimetric Coverage of the Prostate, Normal Tissue Sparing, and Acute Toxicity with High-Dose-Rate Brachytherapy for Large Prostate Volumes

    PubMed Central

    Yang, George; Strom, Tobin J.; Wilder, Richard B.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C.

    2015-01-01

    ABSTRACT Purpose To evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and Methods One hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results Median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p=0.04). There was no ≥ Grade 3 acute toxicity. Conclusions Dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. PMID:26200536

  3. Mortality, Recurrence, and Dependency Rates Are Higher after Acute Ischemic Stroke in Elderly Patients with Diabetes Compared to Younger Patients

    PubMed Central

    Long, Xue; Lou, Yongzhong; Gu, Hongfei; Guo, Xiaofei; Wang, Tao; Zhu, Yanxia; Zhao, Wenjuan; Ning, Xianjia; Li, Bin; Wang, Jinghua; An, Zhongping

    2016-01-01

    Stroke has a greater effect on the elderly than on younger patients. However, the long-term outcomes associated with stroke among elderly patients with diabetes are unknown. We aimed to assess the differences in long-term outcomes between young and elderly stroke patients with diabetes. A total of 3,615 acute ischemic stroke patients with diabetes were recruited for this study between 2006 and 2014. Outcomes at 12 and 36 months after stroke (including mortality, recurrence, and dependency) were compared between younger (age <75 years) and elderly (age ≥75 years) patients. The elderly group included 692 patients (19.1%) overall. Elderly patients were more likely than younger patients to have a Trial of Org 10172 in Acute Stroke Treatment classification of stroke due to cardioembolism, moderate and severe stroke, and atrial fibrillation, but less likely to have hypertension and dyslipidemia, current smokers, and alcohol consumers. Mortality, dependency, and recurrence rates at 12 months after stroke were 19.0, 48.5, and 20.9% in the elderly group and 7.4, 30.9, and 15.4% in the younger group, respectively (all P < 0.05). Corresponding rates at 36 months after stroke were 35.4, 78.7, and 53.8% in the elderly group and 13.7, 61.7, and 43.0% in the younger group, respectively (all P < 0.001). The mortality, dependency, and recurrence rates at 12 and 36 months after stroke were significantly higher in the elderly group than in the younger group after adjusting for stroke subtypes, stroke severity, and risk factors. Odds ratios (95% confidence interval) at 12 and 36 months after stroke were 2.18 (1.64–2.89) and 3.10 (2.35–4.08), respectively, for mortality, all P < 0.001; 1.81 (1.49–2.20) and 2.04 (1.57–2.34), respectively, for dependency, all P < 0.001; and 1.37 (1.06–1.76) and 1.40 (1.07–1.85), respectively, for recurrence, P = 0.016. The findings from this study suggest that management and secondary prevention should be emphasized in elderly patients with

  4. Mortality, Recurrence, and Dependency Rates Are Higher after Acute Ischemic Stroke in Elderly Patients with Diabetes Compared to Younger Patients.

    PubMed

    Long, Xue; Lou, Yongzhong; Gu, Hongfei; Guo, Xiaofei; Wang, Tao; Zhu, Yanxia; Zhao, Wenjuan; Ning, Xianjia; Li, Bin; Wang, Jinghua; An, Zhongping

    2016-01-01

    Stroke has a greater effect on the elderly than on younger patients. However, the long-term outcomes associated with stroke among elderly patients with diabetes are unknown. We aimed to assess the differences in long-term outcomes between young and elderly stroke patients with diabetes. A total of 3,615 acute ischemic stroke patients with diabetes were recruited for this study between 2006 and 2014. Outcomes at 12 and 36 months after stroke (including mortality, recurrence, and dependency) were compared between younger (age <75 years) and elderly (age ≥75 years) patients. The elderly group included 692 patients (19.1%) overall. Elderly patients were more likely than younger patients to have a Trial of Org 10172 in Acute Stroke Treatment classification of stroke due to cardioembolism, moderate and severe stroke, and atrial fibrillation, but less likely to have hypertension and dyslipidemia, current smokers, and alcohol consumers. Mortality, dependency, and recurrence rates at 12 months after stroke were 19.0, 48.5, and 20.9% in the elderly group and 7.4, 30.9, and 15.4% in the younger group, respectively (all P < 0.05). Corresponding rates at 36 months after stroke were 35.4, 78.7, and 53.8% in the elderly group and 13.7, 61.7, and 43.0% in the younger group, respectively (all P < 0.001). The mortality, dependency, and recurrence rates at 12 and 36 months after stroke were significantly higher in the elderly group than in the younger group after adjusting for stroke subtypes, stroke severity, and risk factors. Odds ratios (95% confidence interval) at 12 and 36 months after stroke were 2.18 (1.64-2.89) and 3.10 (2.35-4.08), respectively, for mortality, all P < 0.001; 1.81 (1.49-2.20) and 2.04 (1.57-2.34), respectively, for dependency, all P < 0.001; and 1.37 (1.06-1.76) and 1.40 (1.07-1.85), respectively, for recurrence, P = 0.016. The findings from this study suggest that management and secondary prevention should be emphasized in elderly patients with diabetes in

  5. Sex-specific action of insulin to acutely increase the metabolic clearance rate of dehydroepiandrosterone in humans.

    PubMed Central

    Nestler, J E; Kahwash, Z

    1994-01-01

    To test the hypothesis that insulin acutely enhances the metabolic clearance rate (MCR) of dehydroepiandrosterone in humans, the effect of a short-term insulin infusion on the MCR of dehydroepiandrosterone was assessed in 10 men and 7 women. After an overnight fast, dehydroepiandrosterone was infused at 3.47 mumol/h for 6.5 h. At 240 min, a hyperinsulinemic-euglycemic clamp was begun by infusing insulin at 21.5 pmol/kg per min for 2.5 h. MCR of dehydroepiandrosterone was calculated at baseline (210-240 min) and during the insulin infusion (360-390 min). A control study was conducted at least 1 wk later, in which 0.45% saline was substituted for the hyperinsulinemic-euglycemic clamp. During the insulin clamp study, serum insulin rose from 34 +/- 2 to 1084 +/- 136 pmol/liter (P = 0.0001) in men and from 40 +/- 5 to 1357 +/- 175 pmol/liter (P = 0.0003) in women, while serum glucose remained constant in both groups. MCR of dehydroepiandrosterone rose in men during the insulin infusion from 2443 +/- 409 to 3599 +/- 500 liters/24 h (P = 0.003), but did not change during the control saline infusion. In contrast, MCR of dehydroepiandrosterone in women did not change in the insulin clamp study during insulin infusion (2526 +/- 495 liters/24 h at baseline vs. 2442 +/- 491 liters/24 h during insulin infusion; P = 0.78). These findings suggest that insulin acutely increases the MCR of dehydroepiandrosterone in men but not in women. PMID:7929824

  6. Acute Radiation Effects on Cardiac Function Detected by Strain Rate Imaging in Breast Cancer Patients

    SciTech Connect

    Erven, Katrien; Jurcut, Ruxandra; Weltens, Caroline; Giusca, Sorin; Ector, Joris; Wildiers, Hans; Van den Bogaert, Walter; Voigt, Jens-Uwe

    2011-04-01

    Purpose: To investigate the occurrence of early radiation-induced changes in regional cardiac function using strain rate imaging (SRI) by tissue Doppler echocardiography. Methods and Materials: We included 20 left-sided and 10 right-sided breast cancer patients receiving radiotherapy (RT) to the breast or chest wall. Standard echocardiography and SRI were performed before RT (baseline), immediately after RT (post-RT), and at 2 months follow-up (FUP) after RT. Regional strain (S) and strain rate (SR) values were obtained from all 18 left ventricular (LV) segments. Data were compared to the regional radiation dose. Results: A reduction in S was observed post-RT and at FUP in left-sided patients (S{sub post-RT}: -17.6 {+-} 1.5%, and S{sub FUP}: -17.4 {+-} 2.3%, vs. S{sub baseline}: -19.5 {+-} 2.1%, p < 0.001) but not in right-sided patients. Within the left-sided patient group, S and SR were significantly reduced after RT in apical LV segments (S{sub post-RT}: -15.3 {+-} 2.5%, and S{sub FUP}: -14.3 {+-} 3.7%, vs. S{sub baseline}: -19.3 {+-} 3.0%, p < 0.01; and SR{sub post-RT}: -1.06 {+-} 0.15 s {sup -1}, and SR{sub FUP}: -1.16 {+-} 0.28 s {sup -1}, vs. SR{sub baseline}: -1.29 {+-} 0.27s {sup -1}, p = 0.01), but not in mid- or basal segments. Furthermore, we observed that segments exposed to more than 3 Gy showed a significant decrease in S after RT (S{sub post-RT}: -16.1 {+-} 1.6%, and S{sub FUP}: -15.8 {+-} 3.4%, vs. S{sub baseline}: -18.9 {+-} 2.6%, p < 0.001). This could not be observed in segments receiving less than 3 Gy. Conclusions: SRI shows a dose-related regional decrease in myocardial function after RT. It might be a useful tool in the evaluation of modern RT techniques, with respect to cardiac toxicity.

  7. Thirty-day in-hospital revascularization and mortality rates after acute myocardial infarction in seven Canadian provinces

    PubMed Central

    Johansen, Helen; Brien, Susan E; Finès, Philippe; Bernier, Julie; Humphries, Karin; Stukel, Therese A; Ghali, William A

    2010-01-01

    BACKGROUND: Recent clinical trials have demonstrated benefit with early revascularization following acute myocardial infarction (AMI). Trends in and the association between early revascularization after (ie, 30 days or fewer) AMI and early death were determined. METHODS AND RESULTS: The Statistics Canada Health Person-Oriented Information Database, consisting of hospital discharge records for seven provinces from the Canadian Institute for Health Information Hospital Morbidity Database, was used. If there was no AMI in the preceding year, the first AMI visit within a fiscal year for a patient 20 years of age or older was included. Times to death in hospital and to revascularization procedures were counted from the admission date of the first AMI visit. Mixed model regression analyses with random slopes were used to assess the relationship between early revascularization and mortality. The overall rate of revascularization within 30 days of AMI increased significantly from 12.5% in 1995 to 37.4% in 2003, while the 30-day mortality rate decreased significantly from 13.5% to 10.6%. There was a linearly decreasing relationship – higher regional use of revascularization was associated with lower mortality in both men and women. CONCLUSIONS: These population-based utilization and outcome findings are consistent with clinical trial evidence of improved 30-day in-hospital mortality with increased early revascularization after AMI. PMID:20847971

  8. Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation

    NASA Astrophysics Data System (ADS)

    Nguyen, T. A. K.; DiGiovanna, J.; Cavuscens, S.; Ranieri, M.; Guinand, N.; van de Berg, R.; Carpaneto, J.; Kingma, H.; Guyot, J.-P.; Micera, S.; Perez Fornos, A.

    2016-08-01

    Objective. The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. Approach. Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. Main results. PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. Significance. Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.

  9. Acute effects of dynamic exercises on the relationship between the motor unit firing rate and the recruitment threshold.

    PubMed

    Ye, Xin; Beck, Travis W; DeFreitas, Jason M; Wages, Nathan P

    2015-04-01

    The aim of this study was to compare the acute effects of concentric versus eccentric exercise on motor control strategies. Fifteen men performed six sets of 10 repetitions of maximal concentric exercises or eccentric isokinetic exercises with their dominant elbow flexors on separate experimental visits. Before and after the exercise, maximal strength testing and submaximal trapezoid isometric contractions (40% of the maximal force) were performed. Both exercise conditions caused significant strength loss in the elbow flexors, but the loss was greater following the eccentric exercise (t=2.401, P=.031). The surface electromyographic signals obtained from the submaximal trapezoid isometric contractions were decomposed into individual motor unit action potential trains. For each submaximal trapezoid isometric contraction, the relationship between the average motor unit firing rate and the recruitment threshold was examined using linear regression analysis. In contrast to the concentric exercise, which did not cause significant changes in the mean linear slope coefficient and y-intercept of the linear regression line, the eccentric exercise resulted in a lower mean linear slope and an increased mean y-intercept, thereby indicating that increasing the firing rates of low-threshold motor units may be more important than recruiting high-threshold motor units to compensate for eccentric exercise-induced strength loss. PMID:25514631

  10. Imaging mouse lung allograft rejection with 1H MRI

    PubMed Central

    Guo, Jinbang; Huang, Howard J.; Wang, Xingan; Wang, Wei; Ellison, Henry; Thomen, Robert P.; Gelman, Andrew E.; Woods, Jason C.

    2014-01-01

    Purpose To demonstrate that longitudinal, non-invasive monitoring via MRI can characterize acute cellular rejection (ACR) in mouse orthotopic lung allografts. Methods Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig vs anti-CD4/anti-CD8 treated groups. A two-dimensional multi-slice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at post-operative days 3, 7 and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures. Results Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 post transplantation (0.046→0.789, P < 0.05), despite large inter-mouse variations; this was consistent with histopathologic evidence of rejection. Compliance of the control-Ig allograft decreased significantly over time (0.013→0.003, P < 0.05), but remained constant in mice treated with anti-CD4/anti-CD8 antibodies. Conclusion Lung allograft rejection in individual mice can be monitored by lung parenchymal signal changes and by lung compliance through MRI. Longitudinal imaging can help us better understand the time course of individual lung allograft rejection and response to treatment. PMID:24954886

  11. A retrospective clinical study of Xinjiang Uygur patients with corneal allograft rejection

    PubMed Central

    Maimaitiming, Reziwan; Yang, Xin; Wupuer, Kelala; Ye, Nan; Kong, Na; Gu, Baoyu; Fan, Yuanyuan; Shao, Lan; Pan, Zhiqiang

    2015-01-01

    Background: To explore the causes of corneal allograft rejection in Xinjiang Uygur patients and the factors that affect rejection through a retrospective clinical analysis. Methods: A retrospective analysis of 126 Uygur cases from January 2010 to November 2014 in which corneal transplantation had been performed at the Xinjiang Urumqi ENT hospital. Of the treated patients, 85 eyes belonged to male patients and 41 eyes belonged to female patients. Patients were aged 10-77 years (mean age 46.14 ± 8.20 years). Surgical methods included penetrating keratoplasty (75 eyes) and lamellar keratoplasty (38 eyes). Follow-up time ranged from 0.5 to 3 years and a total of seven pre-operative keratopathies were observed: walleye, corneal ulcer, bullous keratopathy, corneal degeneration. Eye changes included 72 cases of limbal vascularization and 15 cases of high intraocular pressure. Allograft rejection was observed in 25 eyes. Results: The pre-operative keratopathies associated with the highest incidences of allograft rejection were: viral corneal ulcer, bullous keratopathy, adhesive walleye, and fungal corneal ulcers. The rate of allograft rejection using avascular corneal tissue was 10%, while the rate was 36% with severly-vascularized cornea. The earliest time of rejection was 20 days after surgery, while the latest was 16.4 months after surgery. Heavy corneal vascularization is associated with more rapid post-operative rejection. The rate of allograft rejection was higher after combined surgery when compared to penetrating keratoplasty or lamellar keratoplasty alone, while the rate was higher with penetrating keratoplasty than with lamellar keratoplasty. With increasing graft diameter, there was an increase in post-operative allograft rejection. Allograft rejection was significantly increased when graft diameter was above 7.75 mm. Conclusion: The major cause of corneal allograft rejection is viral corneal ulcers. High corneal vascularization, combined surgical methods

  12. Immune response and histology of humoral rejection in kidney transplantation.

    PubMed

    González-Molina, Miguel; Ruiz-Esteban, Pedro; Caballero, Abelardo; Burgos, Dolores; Cabello, Mercedes; Leon, Miriam; Fuentes, Laura; Hernandez, Domingo

    2016-01-01

    The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ. PMID:27267916

  13. Alcohol and its acute effects on resting metabolic rate and diet-induced thermogenesis.

    PubMed

    Weststrate, J A; Wunnink, I; Deurenberg, P; Hautvast, J G

    1990-09-01

    The impact of alcohol (ethanol) on resting energy expenditure of male non-obese volunteers was determined in two studies. In the first study the thermic effect of alcohol on resting metabolic rate (RMR) was assessed in ten male non-obese volunteers. In the second study the impact of alcohol on diet-induced thermogenesis (DIT) was determined in twelve male non-obese volunteers. Energy expenditure was measured with a ventilated-hood system. RMR was measured for 60 min with the subjects in a fasting state. In the first study subjects received in random order 20 g alcohol in concentrations of 75, 180 and 300 ml/l water respectively. After measurement of the RMR the thermic effect of alcohol was measured for 90 min. In the second study volunteers received in random order and in duplicate either a meal of food (2 MJ) plus an alcoholic aperitif (20 g alcohol in a 180 ml/l solution) or an isoenergetic meal of food alone (2.55 MJ) plus a placebo aperitif containing no alcohol. DIT was measured for 240 min. Alcohol induced a significant thermic effect, which varied between 0.22 and 0.30 kJ/min. No systematic difference in DIT was observed among the different concentrations. DIT was not significantly affected by the ingestion of alcohol. Total DIT was 219 (SE 14) kJ for the alcohol treatment and 185 (SE 20) kJ for the control treatment. The results do not support the suggestion that alcohol is less efficiently used as an energy source in comparison with, for example, fats and carbohydrates. PMID:2121268

  14. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Rejected milk. 58.136 Section 58.136 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Milk § 58.136 Rejected milk. A plant shall reject specific milk from a producer if the milk fails...

  15. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Rejected milk. 58.136 Section 58.136 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Milk § 58.136 Rejected milk. A plant shall reject specific milk from a producer if the milk fails...

  16. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rejected milk. 58.136 Section 58.136 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Milk § 58.136 Rejected milk. A plant shall reject specific milk from a producer if the milk fails...

  17. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Rejected milk. 58.136 Section 58.136 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Milk § 58.136 Rejected milk. A plant shall reject specific milk from a producer if the milk fails...

  18. Social Causes and Consequences of Rejection Sensitivity

    ERIC Educational Resources Information Center

    London, Bonita; Downey, Geraldine; Bonica, Cheryl; Paltin, Iris

    2007-01-01

    Predictions from the Rejection Sensitivity (RS) model concerning the social causes and consequences of RS were examined in a longitudinal study of 150 middle school students. Peer nominations of rejection, self-report measures of anxious and angry rejection expectations, and social anxiety, social withdrawal, and loneliness were assessed at two…

  19. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Rejected milk. 58.136 Section 58.136 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Milk § 58.136 Rejected milk. A plant shall reject specific milk from a producer if the milk fails...

  20. Molecular analysis of transplant rejection: marching onward

    PubMed Central

    Lakkis, Fadi G.

    2013-01-01

    Transcriptional profiling of organ transplants is increasingly defining the biological pathways responsible for graft rejection at the molecular level and identifying gene transcripts that diagnose or predict rejection. These advances hold significant promise for the treatment of organ rejection and for improving clinical outcomes after transplantation, but hurdles remain. PMID:24145950

  1. Beneficial Immune Effects of Myeloid-Related Proteins in Kidney Transplant Rejection.

    PubMed

    Rekers, N V; Bajema, I M; Mallat, M J K; Petersen, B; Anholts, J D H; Swings, G M J S; van Miert, P P M C; Kerkhoff, C; Roth, J; Popp, D; van Groningen, M C; Baeten, D; Goemaere, N; Kraaij, M D; Zandbergen, M; Heidt, S; van Kooten, C; de Fijter, J W; Claas, F H J; Eikmans, M

    2016-05-01

    Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303 biopsies before and after transplantation from 190 patients. In two independent cohorts of patients with acute rejection (n = 98 and n = 11; mostly cellular rejections), high expression of S100 calcium-binding protein A8 (S100A8) and A9 (S100A9) was related to improved graft outcome. Mechanisms of action of the S100 molecules were investigated. In the graft and peripheral blood cells, S100A8 and S100A9 expression correlated with myeloid-derived suppressor markers. In line with this finding, recombinant S100A8 and S100A9 proteins inhibited maturation and the allogeneic T cell stimulatory capacity of dendritic cells. S100A9 enhanced the production of reactive oxygen species by macrophages, which suppressed T cell activity at low concentrations in the form of hydrogen peroxide. Intragraft S100A8 and S100A9 expression linked to reduced expression of T cell immunity and tissue injury markers and higher expression of immune regulatory molecules. This study sheds new light on the importance of myeloid cell subsets in directing the outcome of T cell-mediated acute rejection. PMID:26607974

  2. Peripheral blood T Regulatory cell counts may not predict transplant rejection

    PubMed Central

    2010-01-01

    Background Recent evidence shows that allograft survival rates show a positive correlation with the number of circulating T regulatory cells (Tregs). This study investigated both the number and the cytokine profiles exhibited by Foxp3+ Tregs in blood, spleen and lymph nodes of Lewis rat recipients of BN rat cardiac allografts after a single-dose of Rapamycin (RAPA). Results Rats were divided into three groups: control group (containing healthy control and acute rejection group), and recipients treated with a single dose of RAPA on either Day 1 (1D group)or Day 3 (3D group) post-transplant. We analyzed the number of Foxp3+Tregs and the expression of Foxp3 and cytokines in the peripheral blood and the peripheral lymphoid tissues. No difference was found in the numbers of circulating Foxp3+ Tregs between these three groups. RAPA administration significantly increased Foxp3 expression in peripheral lymphoid tissues after a single dose of RAPA on Day 3 post-transplant. Foxp3+Tregs inhibited the activity of effector T cells (Teff) via the secretion of TGF-β1. Conclusion The number of Tregs in the recipient's blood may not be a good predictor of transplant rejection. Foxp3+Tregs inhibit the activity of Teff cells mainly in the peripheral lymphoid tissues. PMID:20633262

  3. A Low Baseline Glomerular Filtration Rate Predicts Poor Clinical Outcome at 3 Months after Acute Ischemic Stroke

    PubMed Central

    Kim, Hyung Jik; Kim, Jwa-Kyung; Oh, Mi Sun; Kim, Sung Gyun; Yu, Kyung-Ho

    2015-01-01

    Background and Purpose Chronic kidney disease (CKD) is an established risk factor for numerous cardiovascular diseases including stroke. The relationship between the baseline estimated glomerular filtration rate (eGFR) and clinical 3-month outcomes in patients with acute ischemic stroke were evaluated in this study. Methods This was a prospective cohort study involving a hospital-based stroke registry; 1373 patients with acute ischemic stroke were enrolled. Patients were divided into the following four groups according their eGFR (calculated using the CKD Epidemiology Collaboration equations): ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. The primary endpoint of poor functional outcome was defined as 3-month death or dependency (modified Rankin Scale score ≥3); secondary endpoints were neurological deterioration (increase in National Institutes of Health Stroke Severity score of ≥4 at discharge compared to baseline) during hospitalization and in-hospital mortality. Results The overall eGFR was 84.5±20.8 mL/min/1.73 m2 (mean±SD). The distribution of baseline renal impairment was as follows: 1,218, 82, 40, and 33 patients had eGFRs of ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. At 3 months after the stroke, 476 (34.7%) patients exhibited poor functional outcome. Furthermore, a poor functional outcome occurred more frequently with increasingly advanced stages of CKD (rates of 31.9%, 53.7%, 55.0%, and 63.6% for CKD stages 1/2, 3a, 3b, and 4/5, respectively; p<0.001). Multivariate analysis revealed that a baseline eGFR of <30 mL/min/1.73m2 increased the risk of a poor functional outcome by 2.37-fold (p=0.047). In addition, baseline renal dysfunction was closely associated with neurological deterioration during hospitalization and with in-hospital mortality. Conclusions A low baseline eGFR was strongly predictive of both poor functional outcome at 3 months after ischemic stroke and neurological deterioration/mortality during hospitalization. PMID

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

    ERIC Educational Resources Information Center

    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…

  5. Acute effects of ozone on heart rate and body temperature in the unanesthetized, unrestrained rat maintained at different ambient temperatures

    SciTech Connect

    Watkinson, W.P.; Aileru, A.A.; Dowd, S.M.; Doerfler, D.L.; Tepper, J.S.

    1993-01-01

    The present studies were conducted to investigate the concentration-response characteristics of acute ozone (O3) exposure on the cardiovascular and thermoregulatory function of the unanesthetized, unrestrained rat, and to examine the modulating effects produced by changes in ambient temperature (T[sub a]) on the induced toxic response. For all studies, groups of male Fischer 344 rats (n=4-6/group) were implanted with radiotelemetry transmitters and allowed to recover overnight. The transmitters permitted continuous monitoring of electrocardiogram (ECG) and body core temperature (T[sub co]); heart rate (HR) was derived from the ECG signal. Frequency of breathing (f) was obtained in selected experiments by means of a Fenn box. All animals were monitored according to the following protocol: control (filtered air; 0.25 h); exposure (O3; 2 h); recovery (filtered air; 3-18 h). For the concentration-response experiments, O3 concentration was varied from 0.25-1.0 ppm and all exposures were conducted at an T[sub a] of 18-20 C. Significant decreases in HR and T[sub co] were demonstrated at O3 concentrations as low as 0.37 ppm.

  6. Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism

    PubMed Central

    Kim, Hyery; Kang, Hyoung Jin; Kim, Hyo Jeong; Jang, Mi Kyung; Kim, Nam Hee; Oh, Yongtaek; Han, Byoung-Don; Choi, Ji-Yeob; Kim, Chul Woo; Lee, Ji Won; Park, Kyung Duk; Shin, Hee Young; Ahn, Hyo Seop

    2012-01-01

    Genetic polymorphisms are important factors in the effects and toxicity of chemotherapeutics. To analyze the pharmacogenetic and ethnic differences in chemotherapeutics, major genes implicated in the treatment of acute lymphoblastic leukemia (ALL) were analyzed. Eighteen loci of 16 genes in 100 patients with ALL were analyzed. The distribution of variant alleles were CYP3A4*1B (0%), CYP3A5*3 (0%), GSTM1 (21%), GSTP1 (21%), GSTT1 (16%), MDR1 exon 21 (77%), MDR1 exon 26 (61%), MTHFR 677 (63%), MTHFR 1298 (29%), NR3C1 1088 (0%), RFC1 80 (68%), TPMT combined genotype (7%), VDR intron 8 (11%), VDR FokI (83%), TYMS enhancer repeat (22%) and ITPA 94 (30%). The frequencies of single nucleotide polymorphisms (SNPs) of 10 loci were statistically different from those in Western Caucasians. Dose percents (actual/planned dose) or toxicity of mercaptopurine and methotrexate were not related to any SNPs. Event free survival (EFS) rate was lower in ITPA variants, and ITPA 94 AC/AA variant genotypes were the only independent risk factor for lower EFS in multivariate analysis, which was a different pharmacogenetic implication from Western studies. This study is the first pharmacogenetic study in Korean pediatric ALL. Our result suggests that there are other possible pharmacogenetic factors besides TPMT or ITPA polymorphisms which influence the metabolism of mercaptopurine in Asian populations. PMID:23029095

  7. Acute effects of three different circuit weight training protocols on blood lactate, heart rate, and rating of perceived exertion in recreationally active women.

    PubMed

    Skidmore, Brook L; Jones, Margaret T; Blegen, Mark; Matthews, Tracey D

    2012-01-01

    Interval and circuit weight training are popular training methods for maximizing time-efficiency, and are purported to deliver greater physiological benefits faster than traditional training methods. Adding interval training into a circuit weight-training workout may further enhance the benefits of circuit weight training by placing increased demands upon the cardiovascular system. Our purpose was to compare acute effects of three circuit weight training protocols 1) traditional circuit weight training, 2) aerobic circuit weight training, and 3) combined circuit weight-interval training on blood lactate (BLA), heart rate (HR), and ratings of perceived exertion (RPE). Eleven recreationally active women completed 7 exercise sessions. Session 1 included measurements of height, weight, estimated VO2max, and 13 repetition maximum (RM) testing of the weight exercises. Sessions 2-4 were held on non-consecutive days for familiarization with traditional circuit weight training (TRAD), aerobic circuit weight training (ACWT), and combined circuit weight-interval training (CWIT) protocols. In sessions 5-7, TRAD, ACWT, and CWIT were performed in a randomized order ≥ 72 hr apart for measures of BLA, HR, and RPE at pre-exercise and following each of three mini-circuit weight training stations. Repeated-measures ANOVAs yielded significant interactions (p < 0.05) in BLA, HR, and RPE. Combined circuit weight-interval training (CWIT) produced higher BLA (7.31 ± 0.37 vs. TRAD: 3.99 ± 0.26, ACWT: 4.54 ± 0.31 mmol.L(-1)), HR (83.51 ± 1.18 vs. TRAD: 70.42 ± 1.67, ACWT: 74.13 ± 1.43 beats.min(-1)) and RPE (8.14 ± 0.41 vs. TRAD: 5.06 ± 0.43, ACWT: 6.15 ± 0.42) at all measures. Aerobic circuit weight training (ACWT) elicited greater RPE than traditional circuit weight training (TRAD) at all measures. Including combined circuit weight-interval training (CWIT) workouts into exercise programming may enhance fitness benefits and maximize time-efficiency more so than traditional

  8. Are You Being Rejected or Excluded? Insights from Neuroimaging Studies Using Different Rejection Paradigms

    PubMed Central

    2012-01-01

    Rejection sensitivity is the heightened tendency to perceive or anxiously expect disengagement from others during social interaction. There has been a recent wave of neuroimaging studies of rejection. The aim of the current review was to determine key brain regions involved in social rejection by selectively reviewing neuroimaging studies that employed one of three paradigms of social rejection, namely social exclusion during a ball-tossing game, evaluating feedback about preference from peers and viewing scenes depicting rejection during social interaction. Across the different paradigms of social rejection, there was concordance in regions for experiencing rejection, namely dorsal anterior cingulate cortex (ACC), subgenual ACC and ventral ACC. Functional dissociation between the regions for experiencing rejection and those for emotion regulation, namely medial prefrontal cortex, ventrolateral prefrontal cortex (VLPFC) and ventral striatum, was evident in the positive association between social distress and regions for experiencing rejection and the inverse association between social distress and the emotion regulation regions. The paradigms of social exclusion and scenes depicting rejection in social interaction were more adept at evoking rejection-specific neural responses. These responses were varyingly influenced by the amount of social distress during the task, social support received, self-esteem and social competence. Presenting rejection cues as scenes of people in social interaction showed high rejection sensitive or schizotypal individuals to under-activate the dorsal ACC and VLPFC, suggesting that such individuals who perceive rejection cues in others down-regulate their response to the perceived rejection by distancing themselves from the scene. PMID:23430682

  9. Effect of an acute necrotic bacterial gill infection and feed deprivation on the metabolic rate of Atlantic salmon Salmo salar.

    PubMed

    Jones, M A; Powell, M D; Becker, J A; Carter, C G

    2007-10-31

    In this study, experiments were conducted to examine the effect of an acute necrotic bacterial gill infection on the metabolic rate (M(O2)) of Atlantic salmon Salmo salar. Fed and unfed Atlantic salmon smolts were exposed to a high concentration (5 x 10(12) CFU ml(-1)) of the bacteria Tenacibaculum maritimum, their routine and maximum metabolic rates (M(O2rout) and M(O2max), respectively) were measured, and relative metabolic scope determined. A significant decrease in metabolic scope was found for both fed and unfed infected groups. Fed infected fish had a mean +/- standard error of the mean (SEM) decrease of 2.21 +/- 0.97 microM O2 g(-1) h(-1), whilst unfed fish a mean +/- SEM decrease of 3.16 +/- 1.29 microM O2 g(-1) h(-1). The decrease in metabolic scope was a result of significantly increased M(O2rout) of both fed and unfed infected salmon. Fed infected fish had a mean +/- SEM increase in M(O2rout) of 1.86 +/- 0.66 microM O2 g(-1) h(-1), whilst unfed infected fish had a mean +/- SEM increase of 2.16 +/- 0.72 microM O2 g(-1) h(-1). Interestingly, all groups maintained M(O2max) regardless of infection status. Increases in M(O2rout) corresponded to a significant increase in blood plasma osmolality. A decrease in metabolic scope has implications for how individuals allocate energy; fish with smaller metabolic scope will have less energy to allocate to functions such as growth, reproduction and immune response, which may adversely affect the efficiency of fish growth. PMID:18159670

  10. Short-term acute effects of gutkha chewing on heart rate variability among young adults: A cross-sectional study

    PubMed Central

    Itagi, Afreen Begum H; Arora, Dimple; Patil, Navin A; Bailwad, Sandeep Anant; Yunus, GY; Goel, Ankit

    2016-01-01

    Background and Objectives: An increase in the consumption of smokeless tobacco has been noticed among high school, college students, and adults. Despite the antiquity and popularity of chewing tobacco in India, its effects have not been investigated systematically in humans. The aim of this study was to investigate acute effects of gutkha chewing on heart rate variability (HRV) among healthy young adults. Materials and Methods: A total of 60 young adult males were included in the study. Each individual was asked to chew tobacco and subjected to HRV analysis. HRV analysis using short-term electrocardiogram recording was used to measure HRV parameters before gutkha chewing and at 5, 15, and 30 min after chewing tobacco. One-way analysis of variance and paired t-test was used to assess changes over time. Results: There was a significant increase in heart rate (HR) during tobacco chewing. Mean HR at baseline measured 73.0 ± 6.2 bpm. There was a rise in mean HR to 83.7 ± 9.1 bpm at 5 min during tobacco chewing and gradual reduction to baseline observed after 15 min followed by no significant change till 30 min. The normalized low-frequency power and LF/high-frequency (HF) power ratio were elevated after 5 min; however, normalized HF power was reduced after 5 min tobacco chewing. Conclusion: Gutkha is closely associated with traditional cardiovascular risk factors as detected by a transient enhancing sympathetic activity during tobacco chewing in the form of increased HRV parameters or an imbalance between sympathetic and parasympathetic neural activity among healthy young adults. PMID:26958522

  11. Egg rejection behavior in a population exposed to parasitism: Village Weavers on Hispaniola

    USGS Publications Warehouse

    Cruz, A.; Prather, J.W.; Wiley, J.W.; Weaver, P.F.

    2008-01-01

    In contrast to African Village Weavers (Ploceus cucullatus) that are parasitized by Diederik Cuckoos (Chrysococcyx caprius), introduced weavers on Hispaniola existed without parasitism for at least 2 centuries until the arrival of the Shiny Cowbird (Molothrus bonariensis) in the 1970s. Cruz and Wiley (1989) found that Hispaniolan weavers had a lower rejection rate of foreign eggs than African populations. Subsequently, Robert and Sorci (1999) and Lahti (2005, 2006) found that acceptance of dissimilar eggs is not characteristic of the species throughout its Hispaniolan range. In 1999-2002, we studied egg rejection in Hispaniolan weavers on a broad regional scale. Rejection increased as experimental eggs became increasingly different from the host eggs. Rejection rates for mimetic eggs, different color eggs, different-spotting eggs, and cowbird eggs was 23.2%, 33.3%, 61.5%, and 85.3%, respectively, with higher rejection of cowbird eggs in areas where cowbirds were observed. Although rejection is likely to have a genetic component, the differences could be due to phenotypic plasticity. Plasticity in egg rejection may be expected, given the potential cost of rejection and the spatiotemporal distribution of cowbirds. Thus, egg rejection has not necessarily decreased in Hispaniolan weavers, but it may act in a plastic manner, increasing where cowbirds are present. ?? The Author 2008. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology. All rights reserved.

  12. [Reciprocity and identity protection: reasons for rejection in the ultimatum game].

    PubMed

    Horita, Yutaka; Yamagishi, Toshio

    2007-10-01

    An ultimatum game and two impunity games, in which rejection by the Responder had no impact on the Proposer's earnings, were conducted with 228 participants. The impunity game was run in two conditions: with feedback information, where the Responder's choice was disclosed to the Proposer, and without feedback information, where the Responder's choice was not disclosed to the Proposer. These two conditions were used to determine whether the motivation for rejection in the impunity game was social punishment or identity protection. The three game conditions and the Responder or Proposer roles were manipulated between participants. The rejection rates in the two impunity games were about half the rate in the ultimatum game: there was no difference in the rejection rates between the two feedback conditions of the impunity game. These results indicate that rejection in the ultimatum game is largely based on identity protection. The adaptive role of maintaining self-image as a commitment device was discussed. PMID:18027592

  13. Traffic-Related Air Pollution and Acute Changes in Heart Rate Variability and Respiratory Function in Urban Cyclists

    PubMed Central

    Kulka, Ryan; Dubeau, Aimee; Martin, Christina; Wang, Daniel; Dales, Robert

    2011-01-01

    Background: Few studies have examined the acute health effects of air pollution exposures experienced while cycling in traffic. Objectives: We conducted a crossover study to examine the relationship between traffic pollution and acute changes in heart rate variability. We also collected spirometry and exhaled nitric oxide measures. Methods: Forty-two healthy adults cycled for 1 hr on high- and low-traffic routes as well as indoors. Health measures were collected before cycling and 1–4 hr after the start of cycling. Ultrafine particles (UFPs; ≤ 0.1 μm in aerodynamic diameter), particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5), black carbon, and volatile organic compounds were measured along each cycling route, and ambient nitrogen dioxide (NO2) and ozone (O3) levels were recorded from a fixed-site monitor. Mixed-effects models were used to estimate associations between air pollutants and changes in health outcome measures relative to precycling baseline values. Results: An interquartile range increase in UFP levels (18,200/cm3) was associated with a significant decrease in high-frequency power 4 hr after the start of cycling [β = –224 msec2; 95% confidence interval (CI), –386 to –63 msec2]. Ambient NO2 levels were inversely associated with the standard deviation of normal-to-normal (NN) intervals (β = –10 msec; 95% CI, –20 to –0.34 msec) and positively associated with the ratio of low-frequency to high-frequency power (β = 1.4; 95% CI, 0.35 to 2.5) 2 hr after the start of cycling. We also observed significant inverse associations between ambient O3 levels and the root mean square of successive differences in adjacent NN intervals 3 hr after the start of cycling. Conclusions: Short-term exposures to traffic pollution may contribute to altered autonomic modulation of the heart in the hours immediately after cycling. PMID:21672679

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

    SciTech Connect

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

    1987-03-01

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

  15. Indirect recognition of MHC class I allopeptides accelerates lung allograft rejection in miniature swine.

    PubMed

    Shoji, Tsuyoshi; Wain, John C; Houser, Stuart L; Benjamin, Louis C; Johnston, Douglas R; Hoerbelt, Ruediger; Hasse, Rebecca S; Lee, Richard S; Muniappan, Ashok; Guenther, Dax A; Bravard, Marjory A; Ledgerwood, Levi G; Sachs, David H; Sayegh, Mohamed H; Madsen, Joren C; Allan, James S

    2005-07-01

    The role of indirect allorecognition in graft rejection is examined in two experiments using a swine lung transplantation model. First, two swine received class I mismatched grafts without immunosuppression; another two recipients were treated postoperatively with cyclosporine (CsA). These swine exhibited acute and chronic rejection, respectively. All four recipients developed T-cell reactivity to donor-derived class I major histocompatibility complex (MHC) peptides. Second, six swine were immunized with synthetic donor-derived class I allopeptides prior to transplantation. Control groups consisted of nonimmunized recipients (n = 6) and recipients immunized with an irrelevant peptide (n = 3). These recipients all received a 12-day course of post-operative CsA. Swine immunized with allopeptides exhibited accelerated graft rejection, as compared to both control groups (p < 0.01 and p = 0.03, respectively). Within the experimental group, the dominant histologic finding was acute rejection (AR). Obliterative bronchiolitis (OB) was seen in the graft with the longest survival. Both control groups showed a lesser degree of AR, with four out of six nonimmunized swine ultimately developing OB. These studies suggest that indirect allorecognition is operative during lung allograft rejection, and that pre-transplant sensitization to donor-derived MHC allopeptides can accelerate graft rejection. PMID:15943620

  16. Proteinuria and Reduced Estimated Glomerular Filtration Rate Independently Predict Risk for Acute Myocardial Infarction: Findings from a Population-Based Study in Keelung, Taiwan

    PubMed Central

    Chang, Shu-Hsuan; Tsai, Chia-Ti; Yen, Amy Ming-Fang; Lei, Meng-Huan; Chen, Hsiu-Hsi; Tseng, Chuen-Den

    2015-01-01

    Background The aim of this study was to evaluate the independent roles of proteinuria and reduced estimated glomerular filtration rate (GFR) in the development of acute myocardial infarction in a northern Taiwanese population. Methods We conducted a community-based prospective cohort study in Keelung, the northernmost county of Taiwan. A total of 63,129 subjects (63% women) ≥ 20 years of age who had no history of coronary heart disease were recruited and followed-up. Univariate and multivariate proportional hazards regression analysis was performed to assess the association between proteinuria and estimated GFR and the risk of acute myocardial infarction. Results There were 305 new cases of acute myocardial infarction (114 women and 191 men) documented during a four-year follow-up period. After adjustment of potential confounding covariates, heavier proteinuria (dipstick urinalysis reading 3+) and estimated GFR of less than 60 ml/min/1.73 m2 independently predicted increased risk of developing acute myocardial infarction. The adjusted hazard ratio (aHR) of heavier proteinuria for occurrence of acute myocardial infarction was 1.85 [95% confidence intervals (CI), 1.17-2.91, p < 0.01] (vs. the reference group: negative dipstick proteinuria). The aHR of estimated GFR of 30-59 ml/min/1.73 m2 for occurrence of acute myocardial infarction was 2.4 (95% CI, 1.31-4.38, p < 0.01) (vs. the reference group: estimated GFR ≥ 90 ml/ min/1.73 m2), and that of estimated GFR of 15-29 ml/min/1.73 m2 was 5.26 (95% CI, 2.26-12.26, p < 0.01). Conclusions We demonstrated that both heavier proteinuria and lower estimated GFR are significant independent predictors of developing future acute myocardial infarction in a northern Taiwanese population. PMID:27122856

  17. Comparing reports of peer rejection: associations with rejection sensitivity, victimization, aggression, and friendship.

    PubMed

    Zimmer-Gembeck, Melanie J; Nesdale, Drew; McGregor, Leanne; Mastro, Shawna; Goodwin, Belinda; Downey, Geraldine

    2013-12-01

    Perceiving that one is rejected is an important correlate of emotional maladjustment. Yet, self-perceptions can substantially differ from classmate-reports of who is rejected. In this study, discrepancies between self- and classmate-reports of rejection were identified in 359 Australian adolescents (age 10-12 years). As expected, adolescents who overestimated rejection reported more rejection sensitivity and felt more victimized by their peers, but were not seen by peers as more victimized. Adolescents who underestimated rejection identified themselves as high in overt aggression, and their peers identified them as high in overt and relational aggression and low in prosocial behavior. Yet, underestimators' feelings of friendship satisfaction did not seem to suffer and they reported low rejection sensitivity. Results suggest that interventions to promote adolescent health should explicitly recognize the different needs of those who do and do not seem to perceive their high rejection, as well as adolescents who overestimate their rejection. PMID:24215970

  18. Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets.

    PubMed

    Bhatti, Adnan Bashir; Usman, Muhammad

    2015-01-01

    The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it. PMID:26677426

  19. Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets

    PubMed Central

    Usman, Muhammad

    2015-01-01

    The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it. PMID:26677426

  20. Post-Exercise Heart Rate Recovery Independently Predicts Clinical Outcome in Patients with Acute Decompensated Heart Failure

    PubMed Central

    Youn, Jong-Chan; Lee, Hye Sun; Choi, Suk-Won; Han, Seong-Woo; Ryu, Kyu-Hyung; Shin, Eui-Cheol; Kang, Seok-Min

    2016-01-01

    Background Post-exercise heart rate recovery (HRR) is an index of parasympathetic function associated with clinical outcome in patients with chronic heart failure. However, its relationship with the pro-inflammatory response and prognostic value in consecutive patients with acute decompensated heart failure (ADHF) has not been investigated. Methods We measured HRR and pro-inflammatory markers in 107 prospectively and consecutively enrolled, recovered ADHF patients (71 male, 59 ± 15 years, mean ejection fraction 28.9 ± 14.2%) during the pre-discharge period. The primary endpoint included cardiovascular (CV) events defined as CV mortality, cardiac transplantation, or rehospitalization due to HF aggravation. Results The CV events occurred in 30 (28.0%) patients (5 cardiovascular deaths and 7 cardiac transplantations) during the follow-up period (median 214 days, 11–812 days). When the patients with ADHF were grouped by HRR according to the Contal and O’Quigley’s method, low HRR was shown to be associated with significantly higher levels of serum monokine-induced by gamma interferon (MIG) and poor clinical outcome. Multivariate Cox regression analysis revealed that low HRR was an independent predictor of CV events in both enter method and stepwise method. The addition of HRR to a model significantly increased predictability for CV events across the entire follow-up period. Conclusion Impaired post-exercise HRR is associated with a pro-inflammatory response and independently predicts clinical outcome in patients with ADHF. These findings may explain the relationship between autonomic dysfunction and clinical outcome in terms of the inflammatory response in these patients. PMID:27135610

  1. Nonalcoholic Fatty Liver Disease Is Associated With Higher 1-year All-Cause Rehospitalization Rates in Patients Admitted for Acute Heart Failure.

    PubMed

    Valbusa, Filippo; Bonapace, Stefano; Grillo, Cristina; Scala, Luca; Chiampan, Andrea; Rossi, Andrea; Zoppini, Giacomo; Lonardo, Amedeo; Arcaro, Guido; Byrne, Christopher D; Targher, Giovanni

    2016-02-01

    Repeat hospitalization due to acute heart failure (HF) is a global public health problem that markedly impacts on health resource use. Identifying novel predictors of rehospitalization would help physicians to determine the optimal postdischarge plan for preventing HF rehospitalization. Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for many heart diseases, including HF. We assessed whether NAFLD at hospital admission predicts 1-year all-cause rehospitalization in patients with acute HF. We enrolled all patients consecutively admitted for acute HF to our General Medicine Division, from January 2013 to April 2014, after excluding patients with acute myocardial infarction, severe heart valve diseases, malignancy, known liver diseases, and those with volume overload related to extracardiac causes. NAFLD was diagnosed by ultrasonography and exclusion of competing etiologies. The primary outcome of the study was the 1-year all-cause rehospitalization rate. Among the 107 patients enrolled in the study, the cumulative rehospitalization rate was 12.1% at 1 month, 25.2% at 3 months, 29.9% at 6 months, and 38.3% at 1 year. Patients with NAFLD had markedly higher 1-year rehospitalization rates than those without NAFLD (58% vs 21% at 1 y; P < 0.001 by the log-rank test). Cox regression analysis revealed that NAFLD was associated with a 5.5-fold increased risk of rehospitalization (adjusted hazard ratio 5.56, 95% confidence interval 2.46-12.1, P < 0.001) after adjustment for multiple HF risk factors and potential confounders. In conclusion, NAFLD was independently associated with higher 1-year rehospitalization in patients hospitalized for acute HF. PMID:26886619

  2. Nonalcoholic Fatty Liver Disease Is Associated With Higher 1-year All-Cause Rehospitalization Rates in Patients Admitted for Acute Heart Failure

    PubMed Central

    Valbusa, Filippo; Bonapace, Stefano; Grillo, Cristina; Scala, Luca; Chiampan, Andrea; Rossi, Andrea; Zoppini, Giacomo; Lonardo, Amedeo; Arcaro, Guido; Byrne, Christopher D.; Targher, Giovanni

    2016-01-01

    Abstract Repeat hospitalization due to acute heart failure (HF) is a global public health problem that markedly impacts on health resource use. Identifying novel predictors of rehospitalization would help physicians to determine the optimal postdischarge plan for preventing HF rehospitalization. Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for many heart diseases, including HF. We assessed whether NAFLD at hospital admission predicts 1-year all-cause rehospitalization in patients with acute HF. We enrolled all patients consecutively admitted for acute HF to our General Medicine Division, from January 2013 to April 2014, after excluding patients with acute myocardial infarction, severe heart valve diseases, malignancy, known liver diseases, and those with volume overload related to extracardiac causes. NAFLD was diagnosed by ultrasonography and exclusion of competing etiologies. The primary outcome of the study was the 1-year all-cause rehospitalization rate. Among the 107 patients enrolled in the study, the cumulative rehospitalization rate was 12.1% at 1 month, 25.2% at 3 months, 29.9% at 6 months, and 38.3% at 1 year. Patients with NAFLD had markedly higher 1-year rehospitalization rates than those without NAFLD (58% vs 21% at 1 y; P < 0.001 by the log-rank test). Cox regression analysis revealed that NAFLD was associated with a 5.5-fold increased risk of rehospitalization (adjusted hazard ratio 5.56, 95% confidence interval 2.46–12.1, P < 0.001) after adjustment for multiple HF risk factors and potential confounders. In conclusion, NAFLD was independently associated with higher 1-year rehospitalization in patients hospitalized for acute HF. PMID:26886619

  3. Role of interleukin-17A in early graft rejection after orthotopic lung transplantation in mice

    PubMed Central

    Chen, Qi-Rui; Wang, Li-Feng; Xia, Si-Si; Zhang, Ya-Mei; Xu, Jiang-Nan

    2016-01-01

    Background The cellular and molecular mechanisms underlying lung allograft rejection remain poorly understood. We investigated the potential role of interleukin (IL)-17A in lung transplant rejection in a mouse model, because previous studies in clinical and rodent models have implicated IL-17A in both acute and chronic rejection. Methods To generate an orthotopic lung transplantation model, lungs from C57BL/6 or BALB/c mice were transplanted into C57BL/6 mice (isograft and allograft models, respectively). The effects of anti-IL-17A treatment in allograft recipients were investigated. The histological features and rejection status of isografts and allografts were assessed at 3, 7, and 28 days after transplantation, and differences in graft infiltrating cells and mRNA expression of relevant cytokines were quantified at 3 and 7 days after transplantation. Results As expected, isografts showed no obvious signs of rejection, whereas allografts exhibited minimal-to-mild rejection (grade A1–A2) by day 3 and moderate-to-severe rejection (grade A3–A4) by day 7, without evidence of obliterative bronchiolitis (OB). However, by 28 days, evidence of OB was observed in 67% (2/3) of allografts and severe rejection (grade A4) was observed in all. IL-17 mRNA expression in allografts was increased with rejection, and interferon (IFN)-γ and IL-6 mRNA expression levels followed a similar pattern. In contrast, IL-22 expression in allografts was only slightly increased. Antibody (Ab) neutralization of IL-17A diminished the signs of acute rejection at 7 days after transplantation in allografts, and this early protection was accompanied by a decrease in cellular stress according to histological evaluation, suggesting the involvement of IL-17A in the development of early post-transplantation lesions. Conclusions Our data indicate that IL-17A is important in the pathophysiology of allograft rejection, and neutralization of IL-17A is a potential therapeutic strategy to preventing lung

  4. Linear and nonlinear analysis of heart rate variability in healthy subjects and after acute myocardial infarction in patients

    PubMed Central

    Kunz, V.C.; Borges, E.N.; Coelho, R.C.; Gubolino, L.A.; Martins, L.E.B.; Silva, E.

    2012-01-01

    The objectives of this study were to evaluate and compare the use of linear and nonlinear methods for analysis of heart rate variability (HRV) in healthy subjects and in patients after acute myocardial infarction (AMI). Heart rate (HR) was recorded for 15 min in the supine position in 10 patients with AMI taking β-blockers (aged 57 ± 9 years) and in 11 healthy subjects (aged 53 ± 4 years). HRV was analyzed in the time domain (RMSSD and RMSM), the frequency domain using low- and high-frequency bands in normalized units (nu; LFnu and HFnu) and the LF/HF ratio and approximate entropy (ApEn) were determined. There was a correlation (P < 0.05) of RMSSD, RMSM, LFnu, HFnu, and the LF/HF ratio index with the ApEn of the AMI group on the 2nd (r = 0.87, 0.65, 0.72, 0.72, and 0.64) and 7th day (r = 0.88, 0.70, 0.69, 0.69, and 0.87) and of the healthy group (r = 0.63, 0.71, 0.63, 0.63, and 0.74), respectively. The median HRV indexes of the AMI group on the 2nd and 7th day differed from the healthy group (P < 0.05): RMSSD = 10.37, 19.95, 24.81; RMSM = 23.47, 31.96, 43.79; LFnu = 0.79, 0.79, 0.62; HFnu = 0.20, 0.20, 0.37; LF/HF ratio = 3.87, 3.94, 1.65; ApEn = 1.01, 1.24, 1.31, respectively. There was agreement between the methods, suggesting that these have the same power to evaluate autonomic modulation of HR in both AMI patients and healthy subjects. AMI contributed to a reduction in cardiac signal irregularity, higher sympathetic modulation and lower vagal modulation. PMID:22370707

  5. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2016-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  6. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2014-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  7. Extended active disturbance rejection controller

    NASA Technical Reports Server (NTRS)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2012-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  8. Fractional active disturbance rejection control.

    PubMed

    Li, Dazi; Ding, Pan; Gao, Zhiqiang

    2016-05-01

    A fractional active disturbance rejection control (FADRC) scheme is proposed to improve the performance of commensurate linear fractional order systems (FOS) and the robust analysis shows that the controller is also applicable to incommensurate linear FOS control. In FADRC, the traditional extended states observer (ESO) is generalized to a fractional order extended states observer (FESO) by using the fractional calculus, and the tracking differentiator plus nonlinear state error feedback are replaced by a fractional proportional-derivative controller. To simplify controller tuning, the linear bandwidth-parameterization method has been adopted. The impacts of the observer bandwidth ωo and controller bandwidth ωc on system performance are then analyzed. Finally, the FADRC stability and frequency-domain characteristics for linear single-input single-output FOS are analyzed. Simulation results by FADRC and ADRC on typical FOS are compared to demonstrate the superiority and effectiveness of the proposed scheme. PMID:26928516

  9. Incidence, etiology, and significance of acute kidney injury in the early post-kidney transplant period.

    PubMed

    Panek, Romuald; Tennankore, Karthik K; Kiberd, Bryce A

    2016-01-01

    Little is known about the incidence, causes, and significance of acute kidney injury (AKI) in the early transplant period. This study used a definition as >26 μmol/L increase in creatinine within 48 h or >50% increase over a period >48 h. In 326 adult consecutive recipients of a solitary kidney transplant from 2006 to 2014 followed at this center, 21% developed AKI within the first six months. Most etiologies were CNI toxicity (33%) or unknown (26%), whereas acute rejection accounted for 17% and urinary tract obstruction for 10%. Those with AKI had a significantly lower glomerular filtration rate (GFR) at one-yr post-transplant (adjusted beta coefficient -5.5 mL/min/1.73 m(2) , 95% CI: -10.4, -0.7, p = 0.025) in a multivariable linear regression model. However, the AKI definition missed 6 of 19 episodes of acute rejection and 4 of 10 episodes of urinary tract obstruction. When acute rejection (including those that did not satisfy AKI criteria) was included in the model, other causes of AKI were not significantly associated with GFR at year 1. Although AKI, using current criteria, is likely to be a significant predictor of later outcomes, important causes are missed and the criteria are not sensitive for clinical decision-making. PMID:26497636

  10. Enhanced cortisol increase upon awakening is associated with greater pain ratings but not salivary cortisol or soluble tumor necrosis factor-α receptor II responses to acute pain

    PubMed Central

    Goodin, Burel R.; Quinn, Noel B.; King, Christopher D.; Page, Gayle G.; Haythornthwaite, Jennifer A.; Edwards, Robert R.; Stapleton, Laura M.; McGuire, Lynanne

    2011-01-01

    Objectives The cortisol awakening response (CAR) is related with psychosocial factors and health in potentially significant ways, suggesting that it may be a distinctive marker of hypothalamic-pituitary-adrenal (HPA) axis function and dysfunction. This sought to expand upon previous work that examined the association between CAR and ratings of laboratory-evoked acute pain stimulation. In addition to evoked pain ratings, this study also tested whether CAR was prospectively related with salivary cortisol and soluble tumor necrosis factor-α receptor II (sTNFαRII) responses to acute pain stimulation. Methods This study included 36 healthy, pain-free volunteers of both sexes recruited via posted study flyers. Prior to completion of laboratory pain testing, salivary cortisol samples were obtained at home over the course of a single morning according to the following time frame: upon awakening, and 15, 30, and 60 min after awakening. Following collection of saliva, study participants brought their home saliva samples to the laboratory for assay and subsequently completed acute experimental pain testing procedures. Results Cluster analysis of CAR revealed two distinct groups with similar patterns of cortisol response to awakening; increased and flattened. Relative to flattened CAR, increased CAR was associated with greater ratings of pain intensity and unpleasantness. Salivary cortisol was significantly increased and sTNFαRII significantly decreased following pain testing, but neither of these responses differed as a function of increased versus flattened CAR. Discussion CAR may be a marker for stress sensitivity and/or the anticipation of impending stress, which could explain why the increased CAR cohort reported greater acute pain ratings. PMID:21904196

  11. Fate of Manuscripts Rejected From the Red Journal

    SciTech Connect

    Holliday, Emma B.; Yang, George; Jagsi, Reshma; Hoffman, Karen E.; Bennett, Katherine Egan; Grace, Calley; Zietman, Anthony L.

    2015-01-01

    Purpose: To evaluate characteristics associated with higher rates of acceptance for original manuscripts submitted for publication to the International Journal of Radiation Oncology • Biology • Physics (IJROBP) and describe the fate of rejected manuscripts. Methods and Materials: Manuscripts submitted to the IJROBP from May 1, 2010, to August 31, 2010, and May 1, 2012, to August 31, 2012, were evaluated for author demographics and acceptance status. A PubMed search was performed for each IJROBP-rejected manuscript to ascertain whether the manuscript was ultimately published elsewhere. The Impact Factor of the accepting journal and the number of citations of the published manuscript were also collected. Results: Of the 500 included manuscripts, 172 (34.4%) were accepted and 328 (65.6%) were rejected. There was no significant difference in acceptance rates according to gender or degree of the submitting author, but there were significant differences seen based on the submitting author's country, rank, and h-index. On multivariate analysis, earlier year submitted (P<.0001) and higher author h-index (P=.006) remained significantly associated with acceptance into the IJROBP. Two hundred thirty-five IJROBP-rejected manuscripts (71.7%) were ultimately published in a PubMed-listed journal as of July 2014. There were no significant differences in any submitting author characteristics. Journals accepting IJROBP-rejected manuscripts had a lower median [interquartile range] 2013 impact factor compared with the IJROBP (2.45 [1.53-3.71] vs 4.176). The IJROBP-rejected manuscripts ultimately published elsewhere had a lower median [interquartile range] number of citations (1 [0-4] vs 6 [2-11]; P<.001), which persisted on multivariate analysis. Conclusions: The acceptance rate for manuscripts submitted to the IJROBP is approximately one-third, and approximately 70% of rejected manuscripts are ultimately published in other PubMed-listed journals, but these ultimate

  12. Effects of Acute Ozone Exposure and Methyl Jasmonate Treatment on White Pine Monoterpene and Sesquiterpene Emission Rates

    NASA Astrophysics Data System (ADS)

    Faiola, C. L.; Wagner, D.; Allwine, E.; Harley, P. C.; Vanreken, T. M.

    2010-12-01

    Biogenic volatile organic compounds (BVOCs) are produced by plants and include monoterpenes, sesquiterpenes, and their oxygenated derivatives. These BVOCs are one of the principal factors influencing the oxidative capacity of the atmosphere in forested regions, and impact both ozone concentration and secondary organic aerosol formation. Under unstressed conditions, the release of BVOCs to the atmosphere is primarily controlled by the vapor pressure of the relevant compounds within the plant tissue, which is in turn dependent on temperature as well as complex biochemical production processes. However, various natural and anthropogenic stressors can alter both the quantity and composition of the BVOCs emitted by plants. Many potential stressors are expected to become stronger as climate change effects escalate. The impacts of most stressors on BVOC emissions have not been well characterized, particularly in a field setting where changes in BVOC emissions could have influential feedbacks with climate. This study investigated the effects of two stressors on monoterpene and sesquiterpene emission rates at a field site in northern Michigan: acute ozone exposure and treatment with methyl jasmonate, an herbivory proxy. The study included six repetitions of the same experiment, each time using a new set of sub-canopy eastern white pine specimens. For each experiment, dynamic branch enclosures were simultaneously used on three specimens for sample collection: one ozone treatment tree, one methyl jasmonate treatment tree, and one control tree. Sampling lines were placed in each enclosure and VOCs were collected onto cartridges packed with Tenax GR adsorbent. Samples were collected several times per day for at least two days before treatment and for five days after treatment. Cartridges were analyzed via thermodesorption with an Agilent GC/MS/FID. This analysis allowed the identification and quantification of several monoterpene and sesquiterpene species in the samples

  13. 21 CFR 1230.47 - Rejected containers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rejected containers. 1230.47 Section 1230.47 Food... FEDERAL CAUSTIC POISON ACT Imports § 1230.47 Rejected containers. (a) In all cases where the containers... notification to the importer that the containers must be exported under customs supervision within 3...

  14. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Rejection. 61.69 Section 61.69 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Specific Rules for Tariff Publications of Dominant and Nondominant Carriers § 61.69 Rejection. When a...

  15. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Rejection. 61.69 Section 61.69 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Specific Rules for Tariff Publications of Dominant and Nondominant Carriers § 61.69 Rejection. When a...

  16. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Rejection. 61.69 Section 61.69 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Specific Rules for Tariff Publications of Dominant and Nondominant Carriers § 61.69 Rejection. When a...

  17. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Rejection. 61.69 Section 61.69 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Specific Rules for Tariff Publications of Dominant and Nondominant Carriers § 61.69 Rejection. When a...

  18. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Rejection. 61.69 Section 61.69 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Specific Rules for Tariff Publications of Dominant and Nondominant Carriers § 61.69 Rejection. When a...

  19. 76 FR 16727 - Proposed Information Collection; Comment Request; Procedures for Acceptance or Rejection of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... Acceptance or Rejection of a Rated Order AGENCY: Bureau of Industry and Security, Commerce. ACTION: Notice... Defense Priorities and Allocations Systems regulation (15 CFR 700) must notify the customer of...

  20. Exceptional ion rejection ability of directional solvent for non-membrane desalination

    SciTech Connect

    Rish, Daniel; Luo, Shirui; Kurtz, Brien; Luo, Tengfei

    2014-01-13

    The recently demonstrated directional solvent extraction (DSE) is promising for very low temperature, membrane-free water desalination. In this paper, we combine atomistic simulations and experimental validation to demonstrate that the currently used directional solvent, decanoic acid, can reject all major salt ions in seawater, with very high rejection rates. The salinities of the DSE recovered water show that ion rejection rates are ∼98%–99%—similar to those of the best reverse osmosis membranes. Our test also shows that the DSE process can desalt seawater to produce fresh water that meets drinking water standards.

  1. Active tracking of rejected dried blood samples in a large program in Nigeria

    PubMed Central

    Inalegwu, Auchi; Phillips, Sunny; Datir, Rawlings; Chime, Christopher; Ozumba, Petronilla; Peters, Samuel; Ogbanufe, Obinna; Mensah, Charles; Abimiku, Alash’Le; Dakum, Patrick; Ndembi, Nicaise

    2016-01-01

    AIM: To study the impact of rejection at different levels of health care by retrospectively reviewing records of dried blood spot samples received at the molecular laboratory for human immunodeficiency virus (HIV) early infant diagnosis (EID) between January 2008 and December 2012. METHODS: The specimen rejection rate, reasons for rejection and the impact of rejection at different levels of health care was examined. The extracted data were cleaned and checked for consistency and then de-duplicated using the unique patient and clinic identifiers. The cleaned data were ciphered and exported to SPSS version 19 (SPSS 2010 IBM Corp, New York, United States) for statistical analyses. RESULTS: Sample rejection rate of 2.4% (n = 786/32552) and repeat rate of 8.8% (n = 69/786) were established. The mean age of infants presenting for first HIV molecular test among accepted valid samples was 17.83 wk (95%CI: 17.65-18.01) vs 20.30 wk (95%CI: 16.53-24.06) for repeated samples. HIV infection rate was 9.8% vs 15.9% for accepted and repeated samples. Compared to tertiary healthcare clinics, secondary and primary clinics had two-fold and three-fold higher likelihood of sample rejection, respectively (P < 0.05). We observed a significant increase in sample rejection rate with increasing number of EID clinics (r = 0.893, P = 0.041). The major reasons for rejection were improper sample collection (26.3%), improper labeling (16.4%) and insufficient blood (14.8%). CONCLUSION: Programs should monitor pre-analytical variables and incorporate continuous quality improvement interventions to reduce errors associated with sample rejection and improve patient retention. PMID:27175352

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

    PubMed

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

    2014-11-01

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

  3. Eculizumab for the Treatment of Severe Antibody-Mediated Rejection: A Case Report and Review of the Literature

    PubMed Central

    Boucher, Anne; Collette, Suzon; Senécal, Lynne

    2016-01-01

    In renal transplantation, treatment options for antibody-mediated rejection are limited. Here, we report a case of severe AMR treated with eculizumab. A 50-year-old woman known for end stage kidney disease secondary to IgA nephropathy received a kidney transplant from a 50-year-old deceased donor. At 5 months after transplantation, she presented with acute graft dysfunction and biopsy showed a severe antibody-mediated rejection associated with thrombotic microangiopathy. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted and the patient was treated with 3 doses of eculizumab. Following the therapy, markers of TMA improved and graft function stabilized. However, ongoing signs of rejection remained in the repeated biopsy. In kidney transplantation, eculizumab is an expensive treatment and its role in the treatment of antibody-mediated rejection remains to be determined. PMID:27478676

  4. Viruses in non-disinfected drinking water from municipal wells are related to community rates of acute gastrointestinal illness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Groundwater supplies for drinking water are frequently contaminated with low-levels of human enteric virus genomes, yet evidence for waterborne disease transmission is lacking. We related qPCR-measured enteric viruses in the tap water of 14 non-chlorinating communities in the U.S. to acute gastroint...

  5. Nutritional repletion of children with severe acute malnutrition does not affect VLDL apolipoprotein B-100 synthesis rate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    VLDL apo B-100 is essential for the secretion of liver fat. It is thought that synthesis of this lipoprotein is impaired in childhood severe acute malnutrition (SAM), especially in the edematous syndromes, and that this contributes to the common occurrence of hepatic steatosis in this condition. How...

  6. TLD skin dose measurements and acute and late effects after lumpectomy and high-dose-rate brachytherapy only for early breast cancer

    SciTech Connect

    Perera, Francisco . E-mail: francisco.perera@lrcc.on.ca; Chisela, Frank; Stitt, Larry; Engel, Jay; Venkatesan, Varagur

    2005-08-01

    Purpose: This report examines the relationships between measured skin doses and the acute and late skin and soft tissue changes in a pilot study of lumpectomy and high-dose-rate brachytherapy only for breast cancer. Methods and Materials: Thirty-seven of 39 women enrolled in this pilot study of high-dose-rate brachytherapy (37.2 Gy in 10 fractions b.i.d.) each had thermoluminescent dosimetry (TLD) at 5 points on the skin of the breast overlying the implant volume. Skin changes at TLD dose points and fibrosis at the lumpectomy site were documented every 6 to 12 months posttreatment using a standardized physician-rated cosmesis questionnaire. The relationships between TLD dose and acute skin reaction, pigmentation, or telangiectasia at 5 years were analyzed using the GEE algorithm and the GENMOD procedure in the SAS statistical package. Fisher's exact test was used to determine whether there were any significant associations between acute skin reaction and late pigmentation or telangiectasia or between the volumes encompassed by various isodoses and fibrosis or fat necrosis. Results: The median TLD dose per fraction (185 dose points) multiplied by 10 was 9.2 Gy. In all 37 patients, acute skin reaction Grade 1 or higher was observed at 5.9% (6 of 102) of dose points receiving 10 Gy or less vs. 44.6% (37 of 83) of dose points receiving more than 10 Gy (p < 0.0001). In 25 patients at 60 months, 1.5% telangiectasia was seen at dose points receiving 10 Gy or less (1 of 69) vs. 18% (10 of 56) telangiectasia at dose points receiving more than 10 Gy (p 0.004). Grade 1 or more pigmentation developed at 1.5% (1 of 69) of dose points receiving less than 10 Gy vs. 25% (14 of 56) of dose points receiving more than 10 Gy (p < 0.001). A Grade 1 or more acute skin reaction was also significantly associated with development of Grade 1 or more pigmentation or telangiectasia at 60 months. This association was most significant for acute reaction and telangiectasia directly over the

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

    PubMed

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

    2015-02-01

    In this study, we showed that aly/aly mice, which are devoid of lymph nodes and Peyer's patches, acutely rejected fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts also were rejected acutely by splenectomized aly/aly (aly/aly-spl(-)) mice devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8(+) T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected by aly/aly-spl(-) mice. Actually, aly/aly-spl(-) mice that spontaneously accepted a heart allotransplant and displayed donor-specific tolerance also accepted skin grafts from the same, but not a third-party, donor via a mechanism involving CD4(+) regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs. PMID:25535285

  8. 43 CFR 3425.1-8 - Rejection of applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Rejection of applications. 3425.1-8... § 3425.1-8 Rejection of applications. (a) An application for a lease shall be rejected in total or in... rejection under paragraph (a) of this section shall not be rejected until the applicant is given...

  9. 43 CFR 3430.5-1 - Rejection of application.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Rejection of application. 3430.5-1 Section... Leases § 3430.5-1 Rejection of application. (a) The authorized officer shall reject the application if... will be rejected; (ii) Of the reasons for the proposed rejection; (iii) That the applicant has 60...

  10. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Notification of rejection. 221.111 Section... PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Rejection of Tariff Publications § 221.111 Notification of rejection... writing that the tariff is rejected and of the reason for such rejection....

  11. 43 CFR 3430.5-1 - Rejection of application.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Rejection of application. 3430.5-1 Section... Leases § 3430.5-1 Rejection of application. (a) The authorized officer shall reject the application if... will be rejected; (ii) Of the reasons for the proposed rejection; (iii) That the applicant has 60...

  12. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Notification of rejection. 221.111 Section... PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Rejection of Tariff Publications § 221.111 Notification of rejection... writing that the tariff is rejected and of the reason for such rejection....

  13. 43 CFR 3430.5-1 - Rejection of application.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Rejection of application. 3430.5-1 Section... Leases § 3430.5-1 Rejection of application. (a) The authorized officer shall reject the application if... will be rejected; (ii) Of the reasons for the proposed rejection; (iii) That the applicant has 60...

  14. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Notification of rejection. 221.111 Section... PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Rejection of Tariff Publications § 221.111 Notification of rejection... writing that the tariff is rejected and of the reason for such rejection....

  15. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Notification of rejection. 221.111 Section... PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Rejection of Tariff Publications § 221.111 Notification of rejection... writing that the tariff is rejected and of the reason for such rejection....

  16. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Notification of rejection. 221.111 Section... PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Rejection of Tariff Publications § 221.111 Notification of rejection... writing that the tariff is rejected and of the reason for such rejection....

  17. 43 CFR 3425.1-8 - Rejection of applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Rejection of applications. 3425.1-8... § 3425.1-8 Rejection of applications. (a) An application for a lease shall be rejected in total or in... rejection under paragraph (a) of this section shall not be rejected until the applicant is given...

  18. 43 CFR 3430.5-1 - Rejection of application.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Rejection of application. 3430.5-1 Section... Leases § 3430.5-1 Rejection of application. (a) The authorized officer shall reject the application if... will be rejected; (ii) Of the reasons for the proposed rejection; (iii) That the applicant has 60...

  19. 43 CFR 3425.1-8 - Rejection of applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Rejection of applications. 3425.1-8... § 3425.1-8 Rejection of applications. (a) An application for a lease shall be rejected in total or in... rejection under paragraph (a) of this section shall not be rejected until the applicant is given...

  20. 43 CFR 3425.1-8 - Rejection of applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Rejection of applications. 3425.1-8... § 3425.1-8 Rejection of applications. (a) An application for a lease shall be rejected in total or in... rejection under paragraph (a) of this section shall not be rejected until the applicant is given...

  1. Comparative analysis of viral genomes from acute and chronic hepatitis B reveals novel variants associated with a lower rate of chronicity.

    PubMed

    Chook, Jack Bee; Ngeow, Yun Fong; Khang, Tsung Fei; Ng, Kee Peng; Tiang, Yee Peng; Mohamed, Rosmawati

    2013-03-01

    Infection with the hepatitis B virus (HBV) may lead to an acute or chronic infection. It is generally accepted that the clinical outcome of infection depends on the balance between host immunity and viral survival strategies. In order to persist, the virus needs to have a high rate of replication and some immune-escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non-fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut-off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five-fold cross-validation. The average prediction accuracy was 61% ± 1%, with a sensitivity of 24% ± 1%, specificity of 98% ± 1%, positive predictive value of 92% ± 4% and negative predictive value of 56% ± 1%. BCP/X, enhancer I and surface/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non-progression to chronic hepatitis. PMID:23297244

  2. The effect of seasonal temperature extremes on sediment rejection in three scleractinian coral species

    NASA Astrophysics Data System (ADS)

    Ganase, A.; Bongaerts, P.; Visser, P. M.; Dove, S. G.

    2016-03-01

    Sedimentation from resuspension following storm surge is a natural occurrence on coral reefs, and scleractinian corals have adapted to effectively reject sediment. However, it is unclear whether the physical ability to reject sedimentation is affected during seasonal temperature extremes. We acclimated three coral species ( Montipora aequituberculata, Lobophyllia corymbosa and Fungia fungites), with different active shedding mechanisms, to three temperature treatments (winter minimum, summer maximum and mean). Corals were then exposed to a sediment rejection experiment in which we measured clearance rates and tissue inflation cycles associated with the clearance of sediment. Temperature impacted clearing rates of M. aequituberculata, which exhibited significantly faster sediment rejection under winter temperatures. Fungia fungites, on the other hand, exhibited significantly higher tissue inflation rates under summer temperatures. Although limited in scope, this study demonstrates that temperature can have a strong effect on the response of corals to sedimentation.

  3. Interplay between Immune responses to HLA and Non-HLA self-antigens in allograft rejection

    PubMed Central

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

    2013-01-01

    Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction. PMID:23876679

  4. Rejection of pharmaceuticals by forward osmosis membranes.

    PubMed

    Jin, Xue; Shan, Junhong; Wang, Can; Wei, Jing; Tang, Chuyang Y

    2012-08-15

    Rejection of four pharmaceutical compounds, carbamazepine, diclofenac, ibuprofen and naproxen, by forward osmosis (FO) membranes was investigated in this study. For the first time, the rejection efficiency of the pharmaceutical compounds was compared between commercial cellulose triacetate (CTA) based membranes and thin film composite (TFC) polyamide based membranes. The rejection behavior was related to membrane interfacial properties, physicochemical characteristics of the pharmaceutical molecules and feed solution pH. TFC polyamide membranes exhibited excellent overall performance, with high water flux, excellent pH stability and great rejection of all pharmaceuticals investigated (>94%). For commercial CTA based FO membranes, hydrophobic interaction between the compounds and membranes exhibited strong influence on their rejection under acidic conditions. The pharmaceuticals rejection was well correlated to their hydrophobicity (log D). Under alkaline conditions, both electrostatic repulsion and size exclusion contributed to the removal of deprotonated molecules. The pharmaceuticals rejection by CTA-HW membrane at pH 8 followed the order: diclofenac (99%)>carbamazepine (95%)>ibuprofen (93%) ≈ naproxen (93%). These results can be important for FO membrane synthesis, modification and their application in water purification. PMID:22640821

  5. Rate of fibrinogen breakdown related to coronary patency and bleeding complications in patients with thrombolysis in acute myocardial infarction--results from the PRIMI trial.

    PubMed

    Ostermann, H; Schmitz-Huebner, U; Windeler, J; Bär, F; Meyer, J; van de Loo, J

    1992-09-01

    Four hundred and one patients with acute myocardial infarction of less than 4 h duration were randomized to receive intravenous thrombolytic treatment with either 80 mg of full length unglycosylated single-chain-urokinase plasminogen activator (INN saruplase) or 1.5 million IU of streptokinase delivered over a 60 min period. Angiographic patency rates were higher at 60 min in saruplase treated patients (71.8% vs 48%; P less than 0.001), but did not differ significantly at 90 min (71.2% vs 63.9%; P = 0.15). Fibrinogen levels dropped markedly in both groups, the decrease being delayed and less pronounced with saruplase. Total fibrin and fibrinogen degradation products and D-dimer values rose earlier and to higher peak values in streptokinase treated patients. In both groups marked plasminogen and alpha 2-antiplasmin consumption was observed. Lower fibrinogen levels, and in particular the faster rate of fibrinogen breakdown, were associated with higher patency rates at 90 min (P less than 0.05). Patients with bleeding complications had lower 'lowest points' and a more rapid decrease in fibrinogen (P less than 0.05). These findings were not related to the drug used. Increased heparin levels at 6 to 12 h were correlated to bleeding complications in streptokinase treated patients. It is concluded that the rate of fibrinogen breakdown during and following thrombolytic treatment for acute myocardial infarction is related to early vessel patency and bleeding complications. PMID:1396833

  6. Determinants of Calcium Infusion Rate During Continuous Veno-venous Hemofiltration with Regional Citrate Anticoagulation in Critically Ill Patients with Acute Kidney Injury

    PubMed Central

    Liu, De-Lin; Huang, Li-Feng; Ma, Wen-Liang; Ding, Qi; Han, Yue; Zheng, Yue; Li, Wen-Xiong

    2016-01-01

    Background: It is unclear that how to decide the calcium infusion rate during continuous veno-venous hemofiltration (CVVH) with regional citrate anticoagulation (RCA). This study aimed to assess the determinants of calcium infusion rate during CVVH with RCA in critically ill patients with acute kidney injury (AKI). Methods: A total of 18 patients with AKI requiring CVVH were prospectively analyzed. Postdilution CVVH was performed with a fixed blood flow rate of 150 ml/min and a replacement fluid flow rate of 2000 ml/h for each new circuit. The infusion of 4% trisodium citrate was started at a rate of 29.9 mmol/h prefilter and adjusted according to postfilter ionized calcium. The infusion of 10% calcium gluconate was initiated at a rate of 5.5 mmol/h and adjusted according to systemic ionized calcium. The infusion rate of trisodium citrate and calcium gluconate as well as ultrafiltrate flow rate were recorded at 1, 2, 4, 6, 12, and 24 h after starting CVVH, respectively. The calcium loss rate by CVVH was also calculated. Results: Fifty-seven sessions of CVVH were performed in 18 AKI patients. The citrate infusion rate, calcium loss rate by CVVH, and calcium infusion rate were 31.30 (interquartile range: 2.70), 4.60 ± 0.48, and 5.50 ± 0.35 mmol/h, respectively. The calcium infusion rate was significantly higher than that of calcium loss rate by CVVH (P < 0.01). The correlation coefficient between the calcium and citrate infusion rates, and calcium infusion and calcium loss rates by CVVH was −0.031 (P > 0.05) and 0.932 (P < 0.01), respectively. In addition, calcium infusion rate (mmol/h) = 1.77 + 0.8 × (calcium loss rate by CVVH, mmol/h). Conclusions: The calcium infusion rate correlates significantly with the calcium loss rate by CVVH but not with the citrate infusion rate in a fixed blood flow rate during CVVH with RCA. PMID:27411455

  7. Acute and Chronic Allograft Dysfunction in Kidney Transplant Recipients.

    PubMed

    Goldberg, Ryan J; Weng, Francis L; Kandula, Praveen

    2016-05-01

    Allograft dysfunction after a kidney transplant is often clinically asymptomatic and is usually detected as an increase in serum creatinine level with corresponding decrease in glomerular filtration rate. The diagnostic evaluation may include blood tests, urinalysis, transplant ultrasonography, radionuclide imaging, and allograft biopsy. Whether it occurs early or later after transplant, allograft dysfunction requires prompt evaluation to determine its cause and subsequent management. Acute rejection, medication toxicity from calcineurin inhibitors, and BK virus nephropathy can occur early or later. Other later causes include transplant glomerulopathy, recurrent glomerulonephritis, and renal artery stenosis. PMID:27095641

  8. Pericytes, microvasular dysfunction and chronic rejection

    PubMed Central

    Kloc, Malgorzata; Kubiak, Jacek Z.; Li, Xian C.; Ghobrial, Rafik M.

    2014-01-01

    Chronic rejection of transplanted organs remains the main obstacle in the long-term success of organ transplantation. Thus, there is a persistent quest for development of anti-chronic rejection therapies and identification of novel molecular and cellular targets. One of the potential targets is the pericytes, the mural cells of microvessels, which regulate microvascular permeability, development and maturation by controlling endothelial cell functions and regulating tissue fibrosis and inflammatory response. In this review we discuss the potential of targeting pericytes in development of microvasular dysfunction and the molecular pathways involved in regulation of pericyte activities for anti-chronic rejection intervention. PMID:25793439

  9. Early subclinical rejection treated with low dose i.v. steroids is not associated to graft survival impairment: 13-years' experience at a single center.

    PubMed

    Gigliotti, Paolo; Lofaro, Danilo; Leone, Francesca; Papalia, Teresa; Senatore, Massimino; Greco, Rosita; Perri, Anna; Vizza, Donatella; Lupinacci, Simona; Toteda, Giuseppina; La Russa, Antonella; De Stefano, Roberto; Romeo, Francesco; Bonofiglio, Renzo

    2016-06-01

    Subclinical rejection (SCR) has been variably associated with reduced graft survival, development and progression of interstitial fibrosis/tubular atrophy and chronic allograft nephropathy, but data are controversial concerning SCR treatment in terms of graft survival improvement. In this single-center retrospective study, we enrolled 174 adult kidney transplant recipients with a protocol biopsy performed at 30 days after transplantation to evaluate the incidence rate and risk factors for early SCR and its impact on 10-year graft survival. Five patients showed primary non function and were excluded. Among 159/169 (94.08 %) patients with stable graft function who underwent protocol biopsy, 17 (10.7 %) showed signs of SCR and were treated with low-dose intravenous (i.v.) steroids. Ten patients showed functional impairment, 8 (4.73 %) resulting as acute rejection. At multivariate analysis, donor age [odds ratio (OR) 1.04, 95 % confidence interval (CI) 1.01-1.09], and delayed graft function (DGF) (OR 1.08, 95 % CI 1.03-1.12) were significantly associated with SCR. The 10-year graft survival rate in the SCR group was similar to that in the normal-findings group (76.5 vs. 74.9 % respectively; p = 0.61). At multivariate Cox regression, acute [hazard ratio (HR) 5.22, 95 % CI 1.70-16.01], but not sub-clinical, rejection was independently associated with long-term graft failure. In conclusion, early protocol biopsy is a useful and safe tool to detect early SCR which seems not to affect the long-term survival. We suggest that this could be, probably, linked to early SCR treatment with low dose i.v. steroids. PMID:25966801

  10. Enhanced B Cell Alloantigen Presentation and Its Epigenetic Dysregulation in Liver Transplant Rejection.

    PubMed

    Ningappa, M; Ashokkumar, C; Higgs, B W; Sun, Q; Jaffe, R; Mazariegos, G; Li, D; Weeks, D E; Subramaniam, S; Ferrell, R; Hakonarson, H; Sindhi, R

    2016-02-01

    T cell suppression prevents acute cellular rejection but causes life-threatening infections and malignancies. Previously, liver transplant (LTx) rejection in children was associated with the single-nucleotide polymorphism (SNP) rs9296068 upstream of the HLA-DOA gene. HLA-DOA inhibits B cell presentation of antigen, a potentially novel antirejection drug target. Using archived samples from 122 white pediatric LTx patients (including 77 described previously), we confirmed the association between rs9296068 and LTx rejection (p = 0.001, odds ratio [OR] 2.55). Next-generation sequencing revealed that the putative transcription factor (CCCTC binding factor [CTCF]) binding SNP locus rs2395304, in linkage disequilibrium with rs9296068 (D' 0.578, r(2) = 0.4), is also associated with LTx rejection (p = 0.008, OR 2.34). Furthermore, LTx rejection is associated with enhanced B cell presentation of donor antigen relative to HLA-nonidentical antigen in a novel cell-based assay and with a downregulated HLA-DOA gene in a subset of these children. In lymphoblastoid B (Raji) cells, rs2395304 coimmunoprecipitates with CTCF, and CTCF knockdown with morpholino antisense oligonucleotides enhances alloantigen presentation and downregulates the HLA-DOA gene, reproducing observations made with HLA-DOA knockdown and clinical rejection. Alloantigen presentation is suppressed by inhibitors of methylation and histone deacetylation, reproducing observations made during resolution of rejection. Enhanced donor antigen presentation by B cells and its epigenetic dysregulation via the HLA-DOA gene represent novel opportunities for surveillance and treatment of transplant rejection. PMID:26663361

  11. Extracorporeal photopheresis in heart transplant rejection.

    PubMed

    Patel, Jignesh; Klapper, Ellen; Shafi, Hedyeh; Kobashigawa, Jon A

    2015-04-01

    Up to 25% of heart transplant recipients develop rejection requiring intervention. While the majority respond to augmentation of immunomodulatory drug therapy, a subset of patients will remain refractory. Extracorporeal photopheresis (ECP) appears particularly useful in the management of select heart transplant recipients at risk of rejection, with recurrent rejection, or rejection associated with hemodynamic compromise. This chapter summarizes the current clinical experience of ECP in heart transplantation. ECP appears to favorably affect both the cellular and humoral arms of the immune response to the allograft and promote a tolerogenic profile. These immunomodulatory effects also appear to decrease development of cardiac allograft vasculopathy. ECP is generally well tolerated with few adverse effects and low infection risk. PMID:25748232

  12. Colorado rejects purchased power approach - looks to planned facilities as basis for capacity payments

    SciTech Connect

    Not Available

    1984-01-01

    The Colorado Public Utility Comission rejected a purchased power proposal based on a mixture of current and anticipated costs in its avoided-cost calculation. The examiner rejected the claim of intervenors that the utility's commitment to build the Pawnee II plant should disqualify its inclusion as an avoided cost. He also rejected the argument that cogenerators and small power producers should receive a credit for avoided line losses. Other decisions involved capacity payment of contracts of 10 years or less and wheeling rates.

  13. Acute Alcohol Consumption and Secondary Psychopathic Traits Increase Ratings of the Attractiveness and Health of Ethnic Ingroup Faces but Not Outgroup Faces

    PubMed Central

    Mitchell, Ian J.; Gillespie, Steven M.; Leverton, Monica; Llewellyn, Victoria; Neale, Emily; Stevenson, Isobel

    2015-01-01

    Studies have consistently shown that both consumption of acute amounts of alcohol and elevated antisocial psychopathic traits are associated with an impaired ability for prepotent response inhibition. This may manifest as a reduced ability to inhibit prepotent race biased responses. Here, we tested the effects of acute alcohol consumption, and elevated antisocial psychopathic traits, on judgments of the attractiveness and health of ethnic ingroup and outgroup faces. In the first study, we show that following acute alcohol consumption, at a dose that is sufficient to result in impaired performance on tests of executive function, Caucasian participants judged White faces to be more attractive and healthier compared to when sober. However, this effect did not extend to Black faces. A similar effect was found in a second study involving sober Caucasian participants where secondary psychopathic traits were related to an intergroup bias in the ratings of attractiveness for White versus Black faces. These results are discussed in terms of a model which postulates that poor prefrontal functioning leads to increases in ingroup liking as a result of impaired abilities for prepotent response inhibition. PMID:25745403

  14. High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

    SciTech Connect

    Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

    1981-11-01

    Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.

  15. DIPS organic rankine cycle heat rejection system

    SciTech Connect

    Pearson, R.

    1987-01-01

    The paper presents the results of an optimization study performed on the heat rejection system for a space based ORC power system using an isotope heat source. The radiator sizing depends on the heat rejection temperature, radiator configuration, and radiator properties such as the fin effectiveness, emissivity, and absorptivity. The optimization analysis to evaluate the effect of each of these parameters on the system weight and area is presented.

  16. Clutter rejection limitations from ambiguous range clutter

    NASA Astrophysics Data System (ADS)

    Reilly, J. Patrick

    Limitations on achievable clutter rejection due to ambiguous range clutter are described. The profile of clutter power versus range is shown to limit achievable clutter rejection. Ambiguous range effects are discussed in the context of sea clutter, using a model that includes propagation conditions, and rain clutter. Limitations in moving target indication systems are illustrated for sea clutter, where propagation is subject to evaporation ducts. Benefits of fill pulses are illustrated for rain and sea clutter.

  17. Abdominal Wall Transplantation: Skin as a Sentinel Marker for Rejection.

    PubMed

    Gerlach, U A; Vrakas, G; Sawitzki, B; Macedo, R; Reddy, S; Friend, P J; Giele, H; Vaidya, A

    2016-06-01

    Abdominal wall transplantation (AWTX) has revolutionized difficult abdominal closure after intestinal transplantation (ITX). More important, the skin of the transplanted abdominal wall (AW) may serve as an immunological tool for differential diagnosis of bowel dysfunction after transplant. Between August 2008 and October 2014, 29 small bowel transplantations were performed in 28 patients (16 male, 12 female; aged 41 ± 13 years). Two groups were identified: the solid organ transplant (SOT) group (n = 15; 12 ITX and 3 modified multivisceral transplantation [MMVTX]) and the SOT-AWTX group (n = 14; 12 ITX and 2 MMVTX), with the latter including one ITX-AWTX retransplantation. Two doses of alemtuzumab were used for induction (30 mg, 6 and 24 h after reperfusion), and tacrolimus (trough levels 8-12 ng/mL) was used for maintenance immunosuppression. Patient survival was similar in both groups (67% vs. 61%); however, the SOT-AWTX group showed faster posttransplant recovery, better intestinal graft survival (79% vs. 60%), a lower intestinal rejection rate (7% vs. 27%) and a lower rate of misdiagnoses in which viral infection was mistaken and treated as rejection (14% vs. 33%). The skin component of the AW may serve as an immune modulator and sentinel marker for immunological activity in the host. This can be a vital tool for timely prevention of intestinal graft rejection and, more important, avoidance of overimmunosuppression in cases of bowel dysfunction not related to graft rejection. PMID:26713513

  18. Design and Modeling of a Variable Heat Rejection Radiator

    NASA Technical Reports Server (NTRS)

    Miller, Jennifer R.; Birur, Gajanana C.; Ganapathi, Gani B.; Sunada, Eric T.; Berisford, Daniel F.; Stephan, Ryan

    2011-01-01

    Variable Heat Rejection Radiator technology needed for future NASA human rated & robotic missions Primary objective is to enable a single loop architecture for human-rated missions (1) Radiators are typically sized for maximum heat load in the warmest continuous environment resulting in a large panel area (2) Large radiator area results in fluid being susceptible to freezing at low load in cold environment and typically results in a two-loop system (3) Dual loop architecture is approximately 18% heavier than single loop architecture (based on Orion thermal control system mass) (4) Single loop architecture requires adaptability to varying environments and heat loads

  19. United States stock market performance and acute myocardial infarction rates in 2008-2009 (from the Duke Databank for Cardiovascular Disease).

    PubMed

    Fiuzat, Mona; Shaw, Linda K; Thomas, Laine; Felker, G Michael; O'Connor, Christopher M

    2010-12-01

    We sought to examine the relation between the United States economic decrease in 2008 and cardiovascular events as measured by local acute myocardial infarction (AMI) rates. Mental stress and traumatic events have been shown to be associated with increased risk of MI in patients with ischemic heart disease. This was an observational study of data from the Duke Databank for Cardiovascular Disease and includes patients undergoing angiography for evaluation of ischemic heart disease from January 2006 to July 2009. Patients with AMI occurring within 3 days before catheterization were used to calculate AMI rates. Stock market values were examined to determine the period of severe economic decrease, and time trends in AMI rates were examined over the same period. Time series models were used to assess the relation between United States stock market National Association of Securities Dealers Automated Quotation (NASDAQ) and rates of AMI. Of 11,590 patients included in the study cohort, 2,465 patients had an AMI during this period. Time series analysis showed a significant increase in AMI rates during a period of stock market decrease from October 2008 to April 2009 (p = 0.003), which remained statistically significant when adjusted for seasons (p = 0.02). In conclusion, unadjusted and adjusted analyses of patients in the Duke Databank for Cardiovascular Disease indicated a significant correlation between a period of stock market decrease and increased AMI rates in our local cohort. PMID:21094353

  20. Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia

    PubMed Central

    Shih, Chia-Jen; Tarng, Der-Cherng; Yang, Wu-Chang; Yang, Chih-Yu

    2014-01-01

    INTRODUCTION Due to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life-threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure. METHODS From January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit. RESULTS Average time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01–3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis. CONCLUSION In RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature. PMID:25091886

  1. Links of justice and rejection sensitivity with aggression in childhood and adolescence.

    PubMed

    Bondü, Rebecca; Krahé, Barbara

    2015-01-01

    Individual differences in justice sensitivity and rejection sensitivity have been linked to differences in aggressive behavior in adults. However, there is little research studying this association in children and adolescents and considering the two constructs in combination. We assessed justice sensitivity from the victim, observer, and perpetrator perspective as well as anxious and angry rejection sensitivity and linked both constructs to different forms (physical, relational), and functions (proactive, reactive) of self-reported aggression and to teacher- and parent-rated aggression in N = 1,489 9- to 19-year olds in Germany. Victim sensitivity and both angry and anxious rejection sensitivity showed positive correlations with all forms and functions of aggression. Angry rejection sensitivity also correlated positively with teacher-rated aggression. Perpetrator sensitivity was negatively correlated with all aggression measures, and observer sensitivity also correlated negatively with all aggression measures except for a positive correlation with reactive aggression. Path models considering the sensitivity facets in combination and controlling for age and gender showed that higher victim justice sensitivity predicted higher aggression on all measures. Higher perpetrator sensitivity predicted lower physical, relational, proactive, and reactive aggression. Higher observer sensitivity predicted lower teacher-rated aggression. Angry rejection sensitivity predicted higher proactive and reactive aggression, whereas anxious rejection sensitivity did not make an additional contribution to the prediction of aggression. The findings are discussed in terms of social information processing models of aggression in childhood and adolescence. PMID:25136820

  2. Micro and nanoparticle drug delivery systems for preventing allotransplant rejection.

    PubMed

    Fisher, James D; Acharya, Abhinav P; Little, Steven R

    2015-09-01

    Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation. PMID:25937032

  3. Absence of dry season Plasmodium parasitaemia, but high rates of reported acute respiratory infection and diarrhoea in preschool-aged children in Kaédi, southern Mauritania

    PubMed Central

    2012-01-01

    Background The epidemiology of malaria in the Senegal River Gorgol valley, southern Mauritania, requires particular attention in the face of ongoing and predicted environmental and climate changes. While “malaria cases” are reported in health facilities throughout the year, past and current climatic and ecological conditions do not favour transmission in the dry season (lack of rainfall and very high temperatures). Moreover, entomological investigations in neighbouring regions point to an absence of malaria transmission in mosquito vectors in the dry season. Because the clinical signs of malaria are non-specific and overlap with those of other diseases (e.g. acute respiratory infections and diarrhoea), new research is needed to better understand malaria transmission patterns in this region to improve adaptive, preventive and curative measures. Methods We conducted a multipurpose cross-sectional survey in the city of Kaédi in April 2011 (dry season), assessing three major disease patterns, including malaria. Plasmodium spp. parasite rates were tested among children aged 6–59 months who were recruited from a random selection of households using a rapid diagnostic test and microscopic examination of Giemsa-stained thick and thin blood films. Acute respiratory infection and diarrhoea were the two other diseases investigated, administering a parental questionnaire to determine the reported prevalence among participating children. Findings No Plasmodium infection was found in any of the 371 surveyed preschool-aged children using two different diagnostic methods. Acute respiratory infections and diarrhoea were reported in 43.4% and 35.0% of the participants, respectively. About two thirds of the children with acute respiratory infections and diarrhoea required medical follow-up by a health worker. Conclusions Malaria was absent in the present dry season survey in the capital of the Gorgol valley of Mauritania, while acute respiratory infections and diarrhea were

  4. Novel Multivariate Methods for Integration of Genomics and Proteomics Data: Applications in a Kidney Transplant Rejection Study

    PubMed Central

    Günther, Oliver P.; Shin, Heesun; Ng, Raymond T.; McMaster, W. Robert; McManus, Bruce M.; Keown, Paul A.; Tebbutt, Scott. J.

    2014-01-01

    Abstract Multi-omics research is a key ingredient of data-intensive life sciences research, permitting measurement of biological molecules at different functional levels in the same individual. For a complete picture at the biological systems level, appropriate statistical techniques must however be developed to integrate different ‘omics’ data sets (e.g., genomics and proteomics). We report here multivariate projection-based analyses approaches to genomics and proteomics data sets, using the case study of and applications to observations in kidney transplant patients who experienced an acute rejection event (n=20) versus non-rejecting controls (n=20). In this data sets, we show how these novel methodologies might serve as promising tools for dimension reduction and selection of relevant features for different analytical frameworks. Unsupervised analyses highlighted the importance of post transplant time-of-rejection, while supervised analyses identified gene and protein signatures that together predicted rejection status with little time effect. The selected genes are part of biological pathways that are representative of immune responses. Gene enrichment profiles revealed increases in innate immune responses and neutrophil activities and a depletion of T lymphocyte related processes in rejection samples as compared to controls. In all, this article offers candidate biomarkers for future detection and monitoring of acute kidney transplant rejection, as well as ways forward for methodological advances to better harness multi-omics data sets. PMID:25387159

  5. Prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction based on gender in Isfahan, Iran (2000-2009)

    PubMed Central

    Mohammadian, Mahdi; Hosseini, Shidokht; Salehiniya, Hamid; Sadeghi, Masoumeh; Sarrafzadegan, Nizal; Roohafza, Hamid Reza; Khazaei, Salman; Soltani, Shahin; Sarrafkia, Ali; Golshahi, Jafar; Mohammadian-Hafshejani, Abdollah

    2015-01-01

    BACKGROUND Determinant prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction (AMI) based on gender in teen year’s period in Isfahan, Iran, was the aim of this study. METHODS This study is a prospective hospital-based study that consisted, all patients with AMI admitted to all hospitals (private and universal hospitals) in Isfahan and Najafabad (Iran) during 2000-2009. To determinant the prognostic factors of 28 days survival rate in patients based on gender, analysis conducted separately for male and female. In analysis, we use of t-test, log Rank tests, Kaplan-Meier method, and univariate and multivariate Cox regression model. RESULTS Short-term (28 days) survival rate was 92.5% in male and 86.7% in female (P < 0.001). The adjusted hazard ratio (HR) of death for age group 80 years and older was 12.7 [95% confidence interval (CI): 5.14-31.3] in male and 8.78 (95% CI: 1.2-63.1) in female. HR for acute transmural MI of the unspecified site in male was 8.9 (95% CI: 4.68-16.97) and in female 9.33 (95% CI: 4.42-19.7). HR for receive of streptokinase in male was 1.11 (95% CI: 0.94-1.31) and in female was 0.69 (95% CI: 0.56-0.84). CONCLUSION Short-term survival rate in male was a higher than female. In male age, anatomic location of MI and hospital status and in female streptokinase use and anatomic location of MI was the most important prognostic factors of survival in-patient with AMI in Isfahan. PMID:26862341

  6. Rejection of false saturation data in optical pulse-oximeter

    NASA Astrophysics Data System (ADS)

    Scalise, Lorenzo; Marchionni, Paolo; Carnielli, Virgilio

    2010-04-01

    Pulse oximetry (PO) is a non-invasive medical device used for monitoring of the arterial oxygen saturation (SaO2) and in particular of haemoglobin oxygenation in blood. Oxygen saturation is commonly used in any setting where the patient blood oxygen saturation is unstable, including Neonatal Intensive Care Unit (NICU). The main factor affecting PO's output data is the presence of voluntary or involuntary motion artifacts or imperfect skin-sensor contact. Various methods have been employed to reject motion artifact but have met with little success. The aim of the present work is to propose a novel measurement procedure for real-time monitoring and validation of the oxygen saturation data as measured in standard pulse oxymeter. The procedure should be able to individuate and reject erroneous saturation data due to incorrect transducer-skin contact or motion artifact. In the case of short sequences of rejected SpO2 data (time duration< 8s), we report on an algorithm able to substitute the sequence of rejected data with the "most-probable" (rescued) SpO2 data. In total we have analyzed 14 patient for a total of 310 hr, 43 min and 15s, equivalent to a total number of samples of 1118595. For our study, we were interested to download heart rate measured with the ECG (HRECG), the heart rate as measured by the pulse oximeter (HRSAT) and the SpO2 value. In order to remove the erroneous SpO2 values reported in the rough data in coincidence of motion artifact (top, right), we have implemented a specific algorithm which provides at the output a new sequence of SpO2 data (validated SpO2 data). With the aim to "rescue" SpO2 value rejected by the previously presented algorithm, we have implemented an algorithm able to provide the "most-probable" SpO2 values in the case of single rejected values or in the case of short sequences of invalidated data (< 8 s). From these data it is possible to observe how in the 6.8% of the observation time the SpO2 data measured by the pulse oximeter

  7. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  8. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  9. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  10. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  11. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  12. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  13. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  14. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  15. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  16. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  17. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  18. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  19. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  20. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  1. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  2. Noninvasive monitoring of infection and rejection after lung transplantation

    PubMed Central

    De Vlaminck, Iwijn; Martin, Lance; Kertesz, Michael; Patel, Kapil; Kowarsky, Mark; Strehl, Calvin; Cohen, Garrett; Luikart, Helen; Neff, Norma F.; Okamoto, Jennifer; Nicolls, Mark R.; Cornfield, David; Weill, David; Valantine, Hannah; Khush, Kiran K.; Quake, Stephen R.

    2015-01-01

    The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.9). We also analyzed the nonhuman cfDNA as a hypothesis-free approach to test for infections. Cytomegalovirus is most frequently assayed clinically, and the levels of CMV-derived sequences in cfDNA are consistent with clinical results. We furthermore show that hypothesis-free monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infectious pathogens such as human herpesvirus (HHV) 6, HHV-7, and adenovirus, which are not often tested clinically, occur with high frequency in this cohort. PMID:26460048

  3. Noninvasive monitoring of infection and rejection after lung transplantation.

    PubMed

    De Vlaminck, Iwijn; Martin, Lance; Kertesz, Michael; Patel, Kapil; Kowarsky, Mark; Strehl, Calvin; Cohen, Garrett; Luikart, Helen; Neff, Norma F; Okamoto, Jennifer; Nicolls, Mark R; Cornfield, David; Weill, David; Valantine, Hannah; Khush, Kiran K; Quake, Stephen R

    2015-10-27

    The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.9). We also analyzed the nonhuman cfDNA as a hypothesis-free approach to test for infections. Cytomegalovirus is most frequently assayed clinically, and the levels of CMV-derived sequences in cfDNA are consistent with clinical results. We furthermore show that hypothesis-free monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infectious pathogens such as human herpesvirus (HHV) 6, HHV-7, and adenovirus, which are not often tested clinically, occur with high frequency in this cohort. PMID:26460048

  4. Belatacept prophylaxis against organ rejection in adult kidney-transplant recipients.

    PubMed

    Del Bello, Arnaud; Marion, Olivier; Milongo, David; Rostaing, Lionel; Kamar, Nassim

    2016-02-01

    End-stage renal disease is a major health problem worldwide, with kidney transplantation being the treatment of choice. Calcineurin inhibitors are still the cornerstone of immunosuppressive therapy. However, they have well-known nephrotoxic affects and increase the risk of cardiovascular disease and cancer. In contrast, belatacept is a biological immunosuppressive agent that inhibits the T-cell co-stimulation. It is approved by the US Food and Drug Administration and the European Medicine Agency for use in adult kidney-transplant recipients to prevent acute rejection. Developmental studies show that belatacept is as efficient as calcineurin inhibitors at preventing acute rejection. In addition, kidney function is better and cardiovascular risk factors are reduced in patients given belatacept. Herein, the authors review the published evidence concerning the efficacy and safety of belatacept and discuss its potential specific indications. PMID:26691282

  5. Rejection of pharmaceuticals by nanofiltration (NF) membranes: Effect of fouling on rejection behaviour

    NASA Astrophysics Data System (ADS)

    Mahlangu, T. O.; Msagati, T. A. M.; Hoek, E. M. V.; Verliefde, A. R. D.; Mamba, B. B.

    The aim of this study was to investigate the effects of membrane fouling by sodium alginate, latex and a combination of alginate + latex on the rejection behaviour of salts and organics. Sodium chloride and caffeine were selected to represent salts and organics, respectively. The effects of the presence of calcium chloride on the fouling behaviour and rejection of solutes were investigated. The results revealed that the salt rejection by virgin membranes was 47% while that of caffeine was 85%. Fouling by alginate, latex and combined alginate-latex resulted in flux decline of 25%, 37% and 17%, respectively. The addition of Ca2+ aggravated fouling and resulted in further flux decline to 37%. Fouling decreased salt rejection, an observation that was further aggravated by the addition on Ca2+. However, it was also observed that fouling with alginate and calcium and with latex and calcium minimised salt rejection by 30% and 31%, respectively. This reduction in salt rejection was attributed to the decrease in permeate flux (since rejection is a function of flux). There was a slight increase in caffeine rejection when the membrane was fouled with latex particles. Moreover, the presence of foulants on the membrane resulted in a decrease in the surface charge of the membrane. The results of this study have shown that the NF 270 membrane can be used to treat water samples contaminated with caffeine and other organic compounds that have physicochemical properties similar to those of caffeine.

  6. The cellular lesion of humoral rejection: predominant recruitment of monocytes to peritubular and glomerular capillaries.

    PubMed

    Fahim, T; Böhmig, G A; Exner, M; Huttary, N; Kerschner, H; Kandutsch, S; Kerjaschki, D; Bramböck, A; Nagy-Bojarszky, K; Regele, H

    2007-02-01

    Accumulation of inflammatory cells within capillaries is a common morphologic feature of humoral renal allograft rejection and is most easily appreciated if it occurs in glomeruli. The aim of our study was to determine the amount and composition of immune cells within glomeruli and peritubular capillaries (PTC) in cellular and humoral allograft rejection. Immunofluorescent double-labeling for CD31 and CD3 or CD68 was used for phenotyping and enumerating immune cells within glomeruli and PTC. The major findings are: (1) accumulation of immune cells in PTC is far more common than it would be anticipated based on the assessment by conventional histology; (2) it is not the absolute number of immune cells accumulating within capillaries, but rather the composition of the intracapillary cell population that distinguishes humoral rejection from cellular rejection and (3) in C4d positive biopsies a predominantly monocytic cell population accumulates not only within glomeruli but also within PTC. The median value of monocyte/T-cell ratio within PTC was 2.3 in C4d positive biopsies but only 1 (p = 0.0008) in C4d negative biopsies. Given their prominent presence within capillaries and their extensive biological versatility monocytes might contribute to the capillary damage observed in acute and chronic allograft rejection. PMID:17283488

  7. Spectral anomaly methods for aerial detection using KUT nuisance rejection

    NASA Astrophysics Data System (ADS)

    Detwiler, R. S.; Pfund, D. M.; Myjak, M. J.; Kulisek, J. A.; Seifert, C. E.

    2015-06-01

    This work discusses the application and optimization of a spectral anomaly method for the real-time detection of gamma radiation sources from an aerial helicopter platform. Aerial detection presents several key challenges over ground-based detection. For one, larger and more rapid background fluctuations are typical due to higher speeds, larger field of view, and geographically induced background changes. As well, the possible large altitude or stand-off distance variations cause significant steps in background count rate as well as spectral changes due to increased gamma-ray scatter with detection at higher altitudes. The work here details the adaptation and optimization of the PNNL-developed algorithm Nuisance-Rejecting Spectral Comparison Ratios for Anomaly Detection (NSCRAD), a spectral anomaly method previously developed for ground-based applications, for an aerial platform. The algorithm has been optimized for two multi-detector systems; a NaI(Tl)-detector-based system and a CsI detector array. The optimization here details the adaptation of the spectral windows for a particular set of target sources to aerial detection and the tailoring for the specific detectors. As well, the methodology and results for background rejection methods optimized for the aerial gamma-ray detection using Potassium, Uranium and Thorium (KUT) nuisance rejection are shown. Results indicate that use of a realistic KUT nuisance rejection may eliminate metric rises due to background magnitude and spectral steps encountered in aerial detection due to altitude changes and geographically induced steps such as at land-water interfaces.

  8. [Chronic rejection: Differences and similarities in various solid organ transplants].

    PubMed

    Suhling, H; Gottlieb, J; Bara, C; Taubert, R; Jäckel, E; Schiffer, M; Bräsen, J H

    2016-01-01

    In this paper, chronic rejections after transplantation of the lungs, heart, liver, and kidney are described. Chronic allograft dysfunction (CAD) plays an important role in all of these transplantations and has a significant influence on patient survival. The pathophysiological reasons for CAD varies greatly in the various organs.Chronic lung allograft dysfunction (CLAD) is the most important determinant of survival and quality of life after lung transplantation. Diagnosis is based on lung function, especially forced expiratory flow in 1 s (FEV1) decline. Prevention, early detection, and rapid treatment are extremely important. Azithromycin and extracorporeal photopheresis are commonly used for treatment because they usually positively influence the progression of lung remodeling.The expression for chronic rejection of the heart is cardiac allograft vasculopathy (CAV). Immunological and nonimmunological factors are important for its development. Due to limited therapeutic options, prevention is of utmost importance (administration of mTOR inhibitors and minimizing cardiovascular risk factors).The mid- and long-term survival rates after liver transplantation have hardly changed in recent decades, which is an indication of the difficulty in diagnosing chronic graft dysfunction. Chronic ductopenic rejection accounts for a small proportion of late graft dysfunction. Idiopathic posttransplant hepatitis and de novo autoimmune hepatitis are important in addition to recurrence of the underlying disease that led to transplantation.Chronic allograft nephropathy is the result of severe rejection which cumulates in increasing fibrosis with remodeling. The earliest possible diagnosis and therapy is currently the only option. Diagnosis is based on evidence of donor-specific antibodies and histological findings. PMID:26782281

  9. Rejection of Cardiac Xenografts Transplanted from α 1,3-Galactosyltransferase Gene-Knockout (GalT-KO) Pigs to Baboons

    PubMed Central

    Hisashi, Y.; Yamada, K.; Kuwaki, K.; Tseng, Y.-L; Dor, F. J. M. F.; Houser, S. L; Robson, S. C.; Schuurman, H.-J.; Cooper, D. K. C.; Sachs, D. H.; Colvin, R. B.; Shimizu, A.

    2010-01-01

    The use of α 1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL+ graft cell injury with the infiltration of T cells (including CD3 and TIA-1+ cytotoxic T cells), CD4+ cells, CD8+ cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL+ dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens. PMID:19032222

  10. Attack rate and household secondary attack rate of acute conjunctivitis during an outbreak in South India: A community-based survey

    PubMed Central

    Thekkur, Pruthu; Reddy, Mahendra M; Naik, Bijaya Nanda; Subitha, L; Kar, Sitanshu Sekhar

    2016-01-01

    Introduction: Knowledge on epidemiology of the disease in the contemporary world will help to develop appropriate strategies to curtail the transmission during an outbreak. This study was carried out during an outbreak of conjunctivitis in selected areas of Puducherry, South India, to assess the attack rate of conjunctivitis, identify factors associated with developing conjunctivitis and calculate household secondary attack rate (HSAR) of conjunctivitis and its correlates. Methodology: During December 2014, a community-based survey was conducted in a selected urban and rural area in Puducherry, South India. Simple random sampling was used to select primary sampling units and systematic sampling to select households. All individuals in the selected households were studied. A questionnaire was used to obtain data on sociodemographic characteristics, conjunctivitis during September-November, 2014, and number of household contacts who developed conjunctivitis within 7 days of index case. The attack rate and HSAR of conjunctivitis was expressed as percentage. Multivariate logistic regression was used to find factors independently associated with developing conjunctivitis and also 100% HSAR. Results: Of 3193 study participants from 772 households, 509 (15.9%, 95% confidence interval 14.7-17.2%) had an attack of conjunctivitis during the reference period. Of the 772 households, 218 (28.2%) had at least one case of conjunctivitis. Of 218 households, 33 (15.1%) households had 100% HSAR. Lower age, not being unemployed, low socioeconomic status, and residing in rural area were independently associated with developing conjunctivitis. Index case being male and living in a household with ≥5 members were independently associated with 100% HSAR. Conclusion: In the outbreak under study, more than one-fourth of households had at least one case of conjunctivitis and about one in every six individuals had an attack of conjunctivitis. PMID:27221677

  11. De novo donor-specific anti-HLA antibodies mediated rejection in liver-transplant patients.

    PubMed

    Del Bello, Arnaud; Congy-Jolivet, Nicolas; Danjoux, Marie; Muscari, Fabrice; Lavayssière, Laurence; Esposito, Laure; Cardeau-Desangles, Isabelle; Guitard, Joëlle; Dörr, Gaëlle; Milongo, David; Suc, Bertrand; Duffas, Jean Pierre; Alric, Laurent; Bureau, Christophe; Guilbeau-Frugier, Céline; Rostaing, Lionel; Kamar, Nassim

    2015-12-01

    The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77) months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody-mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B-cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient- and graft-survival rates did not differ between patients with and without DSAs. In conclusion, liver-transplant patients with liver abnormalities should be screened for DSAs and AMR. PMID:26303035

  12. History of abuse and risky sex among substance users: The role of rejection sensitivity and the need to belong.

    PubMed

    Woerner, Jacqueline; Kopetz, Catalina; Lechner, William V; Lejuez, Carl

    2016-11-01

    This study investigates abuse and rejection sensitivity as important correlates of risky sexual behavior in the context of substance use. Victims of abuse may experience heightened sensitivity to acute social rejection and consequently engage in risky sexual behavior in an attempt to restore belonging. Data were collected from 258 patients at a substance use treatment facility in Washington, D.C. Participants' history of abuse and risky sexual behavior were assessed via self-report. To test the mediating role of rejection sensitivity, participants completed a social rejection task (Cyberball) and responded to a questionnaire assessing their reaction to the rejection experience. General risk-taking propensity was assessed using a computerized lab measure. Abuse was associated with increased rejection sensitivity (B=0.124, SE=0.040, p=0.002), which was in turn associated with increased risky sex (B=0.06, SE=0.028, p=0.03) (indirect effect=0.0075, SE=0.0043; 95% CI [0.0006, 0.0178]), but not with other indices of risk-taking. These findings suggest that rejection sensitivity may be an important mechanism underlying the relationship between abuse and risky sexual behavior among substance users. These effects do not extend to other risk behaviors, supporting the notion that risky sex associated with abuse represents a means to interpersonal connection rather than a general tendency toward self-defeating behavior. PMID:27344009

  13. Batting 300 is Good: Perspectives of Faculty Researchers and their Mentors on Rejection, Resilience, and Persistence in Academic Medical Careers

    PubMed Central

    DeCastro, Rochelle; Sambuco, Dana; Ubel, Peter A.; Stewart, Abigail; Jagsi, Reshma

    2013-01-01

    Purpose Professional rejection is a frequent experience in an academic medical career. The authors sought to understand how rejection affects those pursuing such careers and why some individuals may be more resilient than others in a population of individuals with demonstrated ability and interest in research careers. Method Between February 2010 and August 2011, the authors conducted semi-structured, in-depth telephone interviews with 100 former recipients of National Institutes of Health mentored career development awards and 28 of their mentors. Purposive sampling ensured a diverse range of viewpoints. Multiple analysts thematically coded verbatim transcripts using qualitative data analysis software. Results Participants described a variety of experiences with criticism and rejection in their careers, as well as an acute need for persistence and resilience in the face of such challenges. Through their narratives, participants also vividly described a range of emotional and behavioral responses to their experiences of professional rejection. Their responses illuminated the important roles that various factors, including mentoring and gender, play in shaping the ultimate influence of rejection on their own careers and on the careers of those they have mentored. Conclusions Responses to rejection vary considerably, and negative responses can lead promising individuals to abandon careers in academic medicine. Resilience does not, however, appear to be immutable—it can be learned. Given the frequency of experiences with rejection in academic medicine, strategies such as training mentors to foster resilience may be particularly helpful in improving faculty retention in academic medicine. PMID:23425991

  14. High Mean Fluorescence Intensity Donor-Specific Anti-HLA Antibodies Associated With Chronic Rejection Postliver Transplant

    PubMed Central

    O’Leary, J. G.; Kaneku, H.; Susskind, B. M.; Jennings, L. W.; Neri, M. A.; Davis, G. L.; Klintmalm, G. B.; Terasaki, P. I.

    2015-01-01

    In contrast to kidney transplantation where donorspecific anti-HLA antibodies (DSA) negatively impact graft survival, correlation of DSA with clinical outcomes in patients after orthotopic liver transplantation (OLT) has not been clearly established. We hypothesized that DSA are present in patients who develop chronic rejection after OLT. Prospectively collected serial serum samples on 39 primary OLT patients with biopsy-proven chronic rejection and 39 comparator patients were blinded and analyzed for DSA using LABScreen single antigen beads test, where a 1000 mean fluorescence value was considered positive. In study patients, the median graft survival was 15 months, 74% received ≥ one retransplant, 20% remain alive and 87% had ≥ one episode of acute rejection. This is in contrast to comparator patients where 69% remain alive, and no patient needed retransplant or experienced rejection. Thirty-six chronic rejection patients (92%) and 24 (61%) comparator patients had DSA (p = 0.003). Chronic rejection versus comparator patients had higher mean fluorescence intensity (MFI) DSA. Although a further study with larger numbers of patients is needed to identify clinically significant thresholds, there is an association of high-MFI DSA with chronic rejection after OLT. PMID:21672151

  15. Low-Dose Rituximab Therapy for Antibody-Mediated Rejection in a Highly Sensitized Heart-Transplant Recipient

    PubMed Central

    Aggarwal, Ashim; Pyle, Joseph; Hamilton, John; Bhat, Geetha

    2012-01-01

    Antibody-mediated rejection is the B-cell–mediated production of immunoglobulin G antibody against the transplanted heart. The currently available therapies for antibody-mediated rejection have had marginal success, and chronic manifestations of rejection can result in an increased risk of graft vasculopathy and perhaps require repeat transplantation. Rituximab, a monoclonal antibody directed against the CD20 receptor of B-lymphocytes and approved as therapy for lymphoma, can be used in heart-transplant patients for the management of antibody-mediated rejection. We present the case of a 52-year-old woman with high allosensitization (pre-transplantation panel reactive antibody level, 72%) who underwent successful orthotopic heart transplantation. Postoperatively, her acute antibody-mediated rejection with concomitant cellular rejection was successfully treated with low-dose rituximab. The patient died 5 months later because of multiple other medical problems. The present case suggests a role for low-dose rituximab as therapy for antibody-mediated rejection in heart-transplant patients. PMID:23304051

  16. Validation of a New “Objective Pain Score” Vs. “Numeric Rating Scale” For the Evaluation of Acute Pain: A Comparative Study

    PubMed Central

    Tandon, Manish; Singh, Anshuman; Saluja, Vandana; Dhankhar, Mandeep; Pandey, Chandra Kant; Jain, Priyanka

    2016-01-01

    Background: Pain scores are used for acute pain management. The assessment of pain by the patient as well as the caregiver can be influenced by a variety of factors. The numeric rating scale (NRS) is widely used due to its easy application. The NRS requires abstract thinking by a patient to assign a score to correctly reflect analgesic needs, and its interpretation is subject to bias. Objectives: The study was done to validate a 4-point objective pain score (OPS) for the evaluation of acute postoperative pain and its comparison with the NRS. Patient and Methods: A total of 1021 paired readings of the OPS and NRS of 93 patients who underwent laparotomy and used patient-controlled analgesia were evaluated. Acute pain service (APS) personnel recorded the OPS and NRS. Rescue analgesia was divided into two incremental levels (level 1-paracetamol 1 g for NRS 2 - 5 and OPS 3, Level 2-Fentanyl 25 mcg for NRS ≥ 6 and OPS 1 and 2). In cases of disagreement between the two scores, an independent consultant decided the rescue analgesia. Results: The NRS and OPS agreed across the range of pain. There were 25 disagreements in 8 patients. On 24 occasions, rescue analgesia was increased from level 1 to 2, and one occasion it was decreased from level 2 to 1. On all 25 occasions, the decision to supplement analgesia went in favor of the OPS over the NRS. Besides these 25 disagreements, there were 17 occasions in which observer bias was possible for level 2 rescue analgesia. Conclusions: The OPS is a good stand-alone pain score and is better than the NRS for defining mild and moderate pain. It may even be used to supplement NRS when it is indicative of mild or moderate pain. PMID:27110530

  17. Episodic ozone exposure in adult and senescent Brown Norway rats: acute and delayed effect on heart rate, core temperature and motor activity.

    PubMed

    Gordon, C J; Johnstone, A F; Aydin, C; Phillips, P M; MacPhail, R C; Kodavanti, U P; Ledbetter, A D; Jarema, K A

    2014-06-01

    Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O₃) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O₃ (6 h/day of 1 ppm O₃ for 2 consecutive days/week for 13 weeks). Acute O₃ initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O₃. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O₃ exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O₃, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O₃ exposure. MA was elevated in adults but not senescent rats during recovery from O₃. Overall, acute effects of O₃, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O₃ in senescent rats may explain the relatively heightened physiological response to O₃ in younger rats. PMID:24779854

  18. Predicting 1-Year Mortality Rate for Patients Admitted With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease to an Intensive Care Unit: An Opportunity for Palliative Care

    PubMed Central

    Batzlaff, Cassandra M.; Karpman, Craig; Afessa, Bekele; Benzo, Roberto P.

    2015-01-01

    The objective of this study was to develop a model to aid clinicians in better predicting 1-year mortality rate for patients with an acute exacerbation of chronic obstructive pulmonary disease admitted to the medical intensive care unit (ICU) with the goal of earlier initiation of palliative care and end-of-life communications in this patient population. This retrospective cohort study included patients from a medical ICU from April 1, 1995, to November 30, 2009. Data collected from the Acute Physiology and Chronic Health Evaluation III database included demographic characteristics; severity of illness scores; noninvasive and invasive mechanical ventilation time; ICU and hospital length of stay; and ICU, hospital, and 1-year mortality. Statistically significant univariate variables for 1-year mortality were entered into a multivariate model, and the independent variables were used to generate a scoring system to predict 1-year mortality rate. At 1-year follow-up, 295 of 591 patients died (50%). Age and hospital length of stay were identified as independent determinants of mortality at 1 year by using multivariate analysis, and the predictive model developed had an area under the operating curve of 0.68. Bootstrap analysis with 1000 iterations validated the model, age, and hospital length of stay, entered the model 100% of the time (area under the operating curve=0.687; 95% CI, 0.686–0.688). A simple model using age and hospital length of stay may be informative for providers willing to identify patients with chronic obstructive pulmonary disease with high 1-year mortality rate who may benefit from end-of-life communications and from palliative care. PMID:24656805

  19. Acute effects of advertisements on children's choices, preferences, and ratings of liking for physical activities and sedentary behaviours: a randomised controlled pilot study.

    PubMed

    Atlantis, Evan; Salmon, Jo; Bauman, Adrian

    2008-11-01

    The acute decision prompting effects of social marketing via television (TV) advertisements promoting physical activity to children are unknown. This pilot study aimed to determine the acute effects of an Australian government-sponsored TV advertisement (called 'Get Moving'), promoting more physical activity and less sedentary behaviour, on children's choices, preferences, and ratings of liking for physical activities and sedentary behaviours. Thirty-one children aged 10-12 years were recruited from a single public school, and randomised to one of two treatment groups or two control groups (Solomon four-group design). Treatment participants watched an episode of The Simpsons embedded every 10min with three 30s Get Moving advertisements plus standard advertisements. Control participants watched the same episode plus standard advertisements, but without the Get Moving advertisements. The following dependent variables were assessed immediately before and/or after exposure: activity preference (participants selected either verbally or by pointing to one of eight picture cards depicting four physical activities and four sedentary behaviours); ratings of liking (participants rated how much they liked or disliked each of these activities/behaviours either verbally or by pointing to one of nine values with an adjacent smile or frown on a Likert-type scale); and time spent in physical activities was assessed by direct observation during a 10min free-time session. No significant effects or trends were seen for any of the dependent variables. Further research is needed to determine whether different content and/or higher doses of exposure to physical activity promoting advertisements are needed to influence children's activity choices. PMID:17928265

  20. Low rate of sustained virological response in an outbreak of acute hepatitis C in HIV-infected patients.

    PubMed

    Laguno, Montserrat; Martínez-Rebollar, Maria; Perez, Iñaki; Costa, Josep; Larrousse, Maria; Calvo, Marta; Loncá, Montse; Muñoz, Ana; González-Cordón, Ana; Blanco, José Luís; Martínez, Esteban; Gatell, Josep Maria; Mallolas, Josep

    2012-10-01

    Recent reports have suggested an increased risk of acute hepatitis C (AHC) infection in homosexual HIV-infected men and that early treatment with interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution. A retrospective analysis of 38 HIV-infected patients who were consecutively diagnosed as developing AHC, defined by both seroconversion of anti-hepatitis C virus (HCV) antibodies and detection of serum HCV-RNA in those with previous negative results. Thirty-six patients were men with history of unprotected sexual intercourse with men and two were women with sexual and nosocomial risk factors. AHC infection was asymptomatic in 26 patients; asthenia and jaundice were the most frequent symptoms. HCV genotype 1 was present in 19 patients and genotype 4 in 14 patients. Thirty-five patients received early antiviral treatment with pegylated interferon-alfa associated with ribavirin; 15 of the 32 patients who completed the follow-up (47%) achieved a sustained virological response, as defined by undetectable HCV-RNA 6 months after the end of therapy. There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men. In our experience, early treatment of AHC with pegylated interferon-alfa plus ribavirin in HIV patients achieves poor results. PMID:22428909

  1. Solar dynamic space power system heat rejection

    NASA Technical Reports Server (NTRS)

    Carlson, A. W.; Gustafson, E.; Mclallin, K. L.

    1986-01-01

    A radiator system concept is described that meets the heat rejection requirements of the NASA Space Station solar dynamic power modules. The heat pipe radiator is a high-reliability, high-performance approach that is capable of erection in space and is maintainable on orbit. Results are present of trade studies that compare the radiator system area and weight estimates for candidate advanced high performance heat pipes. The results indicate the advantages of the dual-slot heat pipe radiator for high temperature applications as well as its weight-reduction potential over the range of temperatures to be encountered in the solar dynamic heat rejection systems.

  2. Vitamin D Deficiency Is Associated with Severity of Acute Coronary Syndrome in Patients with Type 2 Diabetes and High Rates of Sun Exposure

    PubMed Central

    Gondim, Fernando; Caribé, Ana; Vasconcelos, Karine Ferreira; Segundo, Alexandre Dantas; Bandeira, Francisco

    2016-01-01

    BACKGROUND Vitamin D deficiency has been associated with cardiovascular risk factors, including type 2 diabetes mellitus (T2DM). Evidence shows that patients with low serum 25-hydroxyvitamin D (25OHD) concentrations have a higher risk of developing coronary artery disease. OBJECTIVE The objective of this study was to assess vitamin D as a predictor of the severity in diabetics with acute coronary syndrome (ACS). METHODS A total of 166 patients were diagnosed with ACS. Serum 25OHD concentrations were analyzed, and risk factors for ACS were evaluated. RESULTS Patients diagnosed as having acute myocardial infarction with elevation of the ST segment had a higher rate of 25OHD, <20 ng/mL compared to ≥30 ng/mL (47.8% × 13.4%, P = 0.03). Diabetics with vitamin D deficiency had more multivessel lesions in the coronary angiography than non-diabetics (69% × 31.8%, P = 0.007). After adjustments for confounders, serum 25OHD remained associated with more severe disease. CONCLUSION Vitamin D deficiency is associated with more severe ACS and is a predictor of more extensive coronary lesions in patients with T2DM. PMID:27625577

  3. Treatment of Antibody-Mediated Rejection After Kidney Transplantation - 10 Years' Experience With Apheresis at a Single Center.

    PubMed

    Gubensek, Jakob; Buturovic-Ponikvar, Jadranka; Kandus, Aljosa; Arnol, Miha; Lindic, Jelka; Kovac, Damjan; Rigler, Andreja Ales; Romozi, Karmen; Ponikvar, Rafael

    2016-06-01

    Antibody-mediated rejection (AMR) is a major cause of kidney graft failure. We aimed to analyze treatment and outcome of AMR in a national cohort of 75 biopsy-proven acute (43 patients, 57%) or chronic active (32 patients, 43%) AMR episodes between 2000 and 2015. The mean patients' age was 46 ± 16 years, the majority was treated with plasma exchange, 4% received immunoadsorption and 7% received both. The majority received pulse methylprednisolone and low-dose CMV hyperimmune globulin, 20% received bortezomib and 13% rituximab. Concomitant infection was treated in 40% of patients. The immediate treatment outcome was successful in 91%, the 1- and 3-year graft survival rates were 71% and 57%, while 3-year patient survival was 97%. Chronic active AMR was associated with worse graft survival than acute AMR (log rank P = 0.06). To conclude, intensive treatment with apheresis and additional immunosuppression was effective in reversing AMR, but long-term graft survival remains markedly decreased, especially in chronic active AMR. PMID:27312908

  4. Acute Effects of a Therapeutic Mobility Device on Physical Activity and Heart Rate in Children with Down Syndrome

    ERIC Educational Resources Information Center

    Hauck, Janet L.; Ulrich, Dale A.

    2015-01-01

    Purpose: The purpose of this feasibility study was to provide an opportunity to increase physical activity (PA) and heart rate (HR) for children with Down syndrome (DS) during unstructured group exercise utilizing a riding device called the Power Pumper®. Method: Twenty-four children aged 5 to 7 years old participated in this case-control study,…

  5. Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

    PubMed Central

    Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

    2014-01-01

    NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

  6. Remote noninvasive allograft rejection monitoring for heart transplant recipients: study protocol for the novel evaluation with home electrocardiogram and remote transmission (NEW HEART) study

    PubMed Central

    2012-01-01

    Background Acute allograft rejection is a major cause of early mortality in the first year after heart transplantation in adults. Although endomyocardial biopsy (EMB) is not a perfect "gold standard" for a correct diagnosis of acute allograft rejection, it is considered the best available test and thus, is the current standard practice. Unfortunately, EMB is an invasive and costly procedure that is not without risk. Recent evidence suggests that acute allograft rejection causes delays in ventricular repolarization and thereby increases the cellular action potential duration resulting in a longer QT interval on the electrocardiogram (ECG). No prospective study to date has investigated whether such increases in the QT interval could provide early detection of acute allograft rejection. Therefore, in the Novel Evaluation With Home Electrocardiogram And Remote Transmission (NEW HEART) study, we plan to investigate the potential benefit of daily home QT interval monitoring to predict acute allograft rejection. Methods/design The NEW HEART study is a prospective, double-blind, multi-center descriptive research study. A sample of 325 adult heart transplant recipients will be recruited within six weeks of transplant from three sites in the United States. Subjects will receive the HeartView™ ECG recorder and its companion Internet Transmitter, which will transmit the subject's ECG to a Core Laboratory. Subjects will be instructed to record and transmit an ECG recording daily for 6 months. An increase in the QTC interval from the previous day of at least 25 ms that persists for 3 consecutive days will be considered abnormal. The number and grade of acute allograft rejection episodes, as well as all-cause mortality, will be collected for one year following transplant surgery. Discussion This study will provide "real world" prospective data to determine the sensitivity and specificity of QTC as an early non invasive marker of cellular rejection in transplant recipients

  7. Changes in Self-Definition Impede Recovery From Rejection.

    PubMed

    Howe, Lauren C; Dweck, Carol S

    2016-01-01

    Previous research highlights how adept people are at emotional recovery after rejection, but less research has examined factors that can prevent full recovery. In five studies, we investigate how changing one's self-definition in response to rejection causes more lasting damage. We demonstrate that people who endorse an entity theory of personality (i.e., personality cannot be changed) report alterations in their self-definitions when reflecting on past rejections (Studies 1, 2, and 3) or imagining novel rejection experiences (Studies 4 and 5). Further, these changes in self-definition hinder post-rejection recovery, causing individuals to feel haunted by their past, that is, to fear the recurrence of rejection and to experience lingering negative affect from the rejection. Thus, beliefs that prompt people to tie experiences of rejection to self-definition cause rejection's impact to linger. PMID:26498977

  8. Bladder (ICRU) dose point does not predict urinary acute toxicity in adjuvant isolated vaginal vault high-dose-rate brachytherapy for intermediate-risk endometrial cancer

    PubMed Central

    Aiza, Antonio; Gomes, Maria José Leite; Chen, Michael Jenwei; Pellizzon, Antonio Cassio de Assis; Mansur, David B.; Baiocchi, Glauco

    2015-01-01

    Purpose High-dose-rate brachytherapy (HDR-BT) alone is an adjuvant treatment option for stage I intermediaterisk endometrial cancer after complete surgical resection. The aim of this study was to determine the value of the dose reported to ICRU bladder point in predicting acute urinary toxicity. Oncologic results are also presented. Material and methods One hundred twenty-six patients were treated with postoperative HDR-BT 24 Gy (4 × 6 Gy) per ICRU guidelines for dose reporting. Cox analysis was used to identify variables that affected local control. The mean bladder point dose was examined for its ability to predict acute urinary toxicity. Results Two patients (1.6%) developed grade 1 gastrointestinal toxicity and 12 patients (9.5%) developed grades 1-2 urinary toxicity. No grade 3 or greater toxicity was observed. The mean bladder point dose was 46.9% (11.256 Gy) and 49.8% (11.952 Gy) for the asymptomatic and symptomatic groups, respectively (p = 0.69). After a median follow-up of 36.8 months, the 3-year local failure and 5-year cancer-specific and overall survival rates were 2.1%, 100%, and 94.6%, respectively. No pelvic failure was seen in this cohort. Age over 60 years (p = 0.48), lymphatic invasion (p = 0.77), FIGO histological grade (p = 0.76), isthmus invasion (p = 0.68), and applicator type (cylinder × ovoid) (p = 0.82) did not significantly affect local control. Conclusions In this retrospective study, ICRU bladder point did not correlate with urinary toxicity. Four fractions of 6 Gy HDR-BT effected satisfactory local control, with acceptable urinary and gastrointestinal toxicity. PMID:26622241

  9. Development of enhanced sulfur rejection processes

    SciTech Connect

    Yoon, R.H.; Luttrell, G.H.; Adel, G.T.; Richardson, P.E.

    1996-03-01

    Research at Virginia Tech led to the development of two complementary concepts for improving the removal of inorganic sulfur from many eastern U.S. coals. These concepts are referred to as Electrochemically Enhanced Sulfur Rejection (EESR) and Polymer Enhanced Sulfur Rejection (PESR) processes. The EESR process uses electrochemical techniques to suppress the formation of hydrophobic oxidation products believed to be responsible for the floatability of coal pyrite. The PESR process uses polymeric reagents that react with pyrite and convert floatable middlings, i.e., composite particles composed of pyrite with coal inclusions, into hydrophilic particles. These new pyritic-sulfur rejection processes do not require significant modifications to existing coal preparation facilities, thereby enhancing their adoptability by the coal industry. It is believed that these processes can be used simultaneously to maximize the rejection of both well-liberated pyrite and composite coal-pyrite particles. The project was initiated on October 1, 1992 and all technical work has been completed. This report is based on the research carried out under Tasks 2-7 described in the project proposal. These tasks include Characterization, Electrochemical Studies, In Situ Monitoring of Reagent Adsorption on Pyrite, Bench Scale Testing of the EESR Process, Bench Scale Testing of the PESR Process, and Modeling and Simulation.

  10. Development of enhanced sulfur rejection processes

    SciTech Connect

    Yoon, R.H.; Luttrell, G.; Adel, G.; Richardson, P.E.

    1993-03-23

    Research at Virginia Tech led to two complementary concepts for improving the removal of inorganic sulfur from much of the Eastern US coals. One controls the surface properties of coal pyrite (FeS[sub 2]) by electrochemical-.potential control, referred to as the Electrochemically Enhanced Sulfur Rejection (EESR) Process: The second controls the flotation of middlings, i.e., particles composed of pyrite with coal inclusions by using polymeric reagents to react with pyrite and convert the middlings to hydrophilic particles, and is termed the Polymer Enhanced Sulfur Rejection (PESR) Process. These new concepts are based on recent research establishing the two main reasons why flotation fails to remove more than about 50% of the pyritic sulfur from coal: superficial oxidization of liberated pyrite to form polysulfide oxidation products so that a part of the liberated pyrite floats with the coal; and hydrophobic coal inclusions in the middlings dominating their flotation so that the middlings also float with the coal. These new pyritic-sulfur rejection processes do not require significant modifications of existing coal preparation facilities, enhancing their adoptability by the coal industry. It is believed that they can be used simultaneously to achieve both free pyrite and locked pyrite rejection.

  11. Nutrition: rejection is the fly's protection.

    PubMed

    Herbert, Samantha L; Ribeiro, Carlos

    2014-03-31

    Animals need to ingest a full set of essential amino acids through their diet. A new study in Drosophila larvae describes how activation of the kinase GCN2 in three dopaminergic neurons mediates the rejection of amino-acid-imbalanced food. PMID:24698377

  12. A Developmental Interpretation of Help Rejection.

    ERIC Educational Resources Information Center

    Silverman, Sharon; Juhasz, Anne M.

    1993-01-01

    Describes a study of factors accounting for low levels of student participation in academic assistance programs, based on case studies of eight university students on academic probation who had rejected offers of academic assistance, using structured interviews and the Erikson Psychosocial Stage Inventory and the Mooney Problem Checklist. Includes…

  13. Examining Social Acceptance & Rejection. FPG Snapshot #44

    ERIC Educational Resources Information Center

    FPG Child Development Institute, 2007

    2007-01-01

    This FPG Snapshot summarizes the findings of a study, published in the November 2006 issue of the "Journal of Educational Psychology," that examined whether children with disabilities are accepted or rejected by their classmates in inclusive classrooms. Specifically, the study examined two sets of related questions: (1) Are individual children…

  14. Antimyosin imaging in cardiac transplant rejection

    SciTech Connect

    Johnson, L.L.; Cannon, P.J. )

    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.

  15. Guidelines for proposals to conserve or reject

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The scientific journal Taxon is the medium for the publication of proposals to conserve or reject scientific names of plants based on the International Code of Botanical Nomenclature (ICBN). The first formal guidelines for the preparation of such proposals appeared in 1994; these were updated in 200...

  16. Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate-mediated attenuation.

    PubMed

    Del Rio, Carlos L; Dawson, Tom A; Clymer, Bradley D; Paterson, David J; Billman, George E

    2008-08-01

    Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia-induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro-arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min(-1)), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 +/- 9 Omega, from 611 +/- 24 Omega, n = 16) when compared with intact control dogs (+43 +/- 5 Omega, from 620 +/- 20 Omega, n = 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 +/- 11 to 193 +/- 15 beats min(-1)) and MEI (+12 +/- 1.1 Omega, from 663 +/- 18 Omega). In contrast, VNS during ischaemia (n = 11) abruptly reduced HR (from 206 +/- 6 to 73 +/- 9 beats min(-1)) and MEI (-16 +/- 2 Omega, from 700 +/- 44 Omega). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG-derived indices of ischaemia (e.g. ST segment, 0.22 +/- 0.03 versus 0.15 +/- 0.03 mV) and of rate-corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 +/- 4.2 versus 65.8 +/- 5.9 ms; QTc, 340 +/- 8 versus 254

  17. Large Solar-Rejection Filter

    NASA Technical Reports Server (NTRS)

    Roberts, William; Sheikh, David; Patrick, Brian

    2007-01-01

    analogous to a bird on a high voltage power wire. Recent analysis confirms that positive floating potentials, ionospheric currents to the EVA suit, can be hazardous. The analysis is wrong in that the ionospheric plasma itself can close the circuit. Parametric analysis of very low voltage exposures (2 to 15 volts) could cause pain and/or involuntary muscle tetani or spinal cord shock. NASA worked with the Naval Health Research Center Detachment Directed Energy Bioeffects Laboratory to examine the affects electrical hazards could have on extravehicular activity using two models. The results of the two computational models were combined to predict areas of the body in which neurons of different diameters would be excited. They predicted that physiologically active current could be conducted across the crew member causing catastrophic hazards. Future work to analyze additional current paths was proposed. The FUSE spectrum of BB Dor, observed in a high state, is modeled with an accretion disk with a very low inclination (possibly lower than 10 degrees). Assuming an average WD mass of 0.8 solar mass leads to a distance of the order of approximately 650pc, consistent with the extremely low galactic reddening in its direction, and a mass accretion rate of 10 (exp -9) solar mass a year. The spectrum presents some broad and deep silicon and sulfur absorption lines, indicating that these elements are over-abundant: silicon is 3 times solar, and sulfur is 20 times solar. The FUSE spectrum of BB Dor, observed in a high state, is modeled with an accretion disk with a very low inclination (possibly lower than 10 degrees). Assuming an average WD mass of 0.8 solar mass leads to a distance of the order of approximately 650pc, consistent with the extremely low galactic reddening in its direction, and a mass accretion rate of 10 (exp -9) solar mass a year. The spectrum presents some broad and deep silicon and sulfur absorption lines, indicating that these elements are over-abundant: silicon is

  18. Short-Term and Two-Year Rate of Recurrent Cerebrovascular Events in Patients with Acute Cerebral Ischemia of Undetermined Aetiology, with and without a Patent Foramen Ovale

    PubMed Central

    Di Legge, Silvia; Sallustio, Fabrizio; De Marchis, Emiliano; Rossi, Costanza; Koch, Giacomo; Diomedi, Marina; Borzi, Mauro; Romeo, Francesco; Stanzione, Paolo

    2011-01-01

    Purpose. We investigated stroke recurrence in patients with acute ischemic stroke of undetermined aetiology, with or without a patent foramen ovale (PFO). Methods. Consecutive stroke patients underwent to Transcranial Doppler and Transesophageal Echocardiography for PFO detection. Secondary stroke prevention was based on current guidelines. Results. PFO was detected in 57/129 (44%) patients. The rate of recurrent stroke did not significantly differ between patients with and without a PFO: 0.0% versus 1.4% (1 week), 1.7% versus 2.7% (1 month), and 3.5% versus 4.2% (3 months), respectively. The 2-year rates were 10.4% (5/48) in medically treated PFO and 8.3% (6/72) in PFO-negative patients (P = 0.65), with a relative risk of 1.25. No recurrent events occurred in 9 patients treated with percutaneous closure of PFO. Conclusion. PFO was not associated with increased rate of recurrent stroke. Age-related factors associated with stroke recurrence in cryptogenic stroke should be taken into account when patients older than 55 years are included in PFO studies. PMID:22389838

  19. Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation

    PubMed Central

    Bourier, Felix; Kühne, Louisa; Banas, Miriam C.; Rümmele, Petra; Wurm, Simone; Banas, Bernhard

    2016-01-01

    Objective Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation. Results Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median) was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival. Conclusion The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis

  20. Neural Changes Associated with Emotion Processing in Children Experiencing Peer Rejection: A Functional MRI Study

    PubMed Central

    Lee, Kyoung-Uk

    2014-01-01

    This study was performed to investigate differences between children who did and did not experience peer rejection in psychological state through surveys and in emotion processing during an interpersonal stress challenge task to reflect naturalistic interpersonal face-to-face relationships. A total of 20 right-handed children, 10 to 12 yr of age, completed self-rating questionnaires inquiring about peer rejection in school, depression, and anxiety. They then underwent an interpersonal stress challenge task simulating conditions of emotional stress, in reaction to positive, negative and neutral facial expression stimuli, using interpersonal feedbacks, and functional magnetic resonance imaging (FMRI) for an analysis of neural correlates during the task. Ten were the peer-rejection group, whereas the remainder were the control group. Based on the behavioral results, the peer-rejection group exhibited elevated levels of depression, state anxiety, trait anxiety and social anxiety as compared to the control group. The FMRI results revealed that the peer-rejection group exhibited greater and remarkably more extensive activation of brain regions encompassing the amygdala, orbitofrontal cortex and ventrolateral prefrontal cortex in response to negative feedback stimuli of emotional faces. The different brain reactivities characterizing emotion processing during interpersonal relationships may be present between children who do and do not experience peer rejection. Graphical Abstract PMID:25246750

  1. Transfusion Induced Bone Marrow Transplant Rejection Due to Minor Histocompatibility Antigens

    PubMed Central

    Patel, Seema R; Zimring, James C

    2014-01-01

    Traditionally, alloimmunization to transfused blood products has focused exclusively upon recipient antibodies recognizing donor alloantigens present on the cell surface. Accordingly, the immunological sequelae of alloimmunization have been antibody mediated effects (i.e. hemolytic transfusion reactions, platelet refractoriness, anti-HLA and anti-HNA effects, etc.). However, in addition to the above sequelae, there is also a correlation between the number of antecedent transfusions in humans and the rate of bone marrow transplant (BMT) rejection - under reduced intensity conditioning with HLA matched or HLA identical marrow. BMT of this nature is the only existing cure for a series of non-malignant hematological diseases (e.g. sickle cell disease, thalassemias, etc.); however, rejection remains a clinical problem. It has been hypothesized that transfusion induces subsequent BMT rejection through immunization. Studies in animal models have observed the same effect and have demonstrated that transfusion induced BMT rejection can occur in response to alloimmunization. However, unlike traditional antibody responses, sensitization in this case results in cellular immune effects, involving populations such as T cell or NK cells. In this case, rejection occurs in the absence of alloantibodies, and would not be detected by existing immune-hematological methods. We review human and animal studies in light of the hypothesis that, for distinct clinical populations, enhanced rejection of BMT may be an unappreciated adverse consequence of transfusion which current blood bank methodologies are unable to detect. PMID:24090731

  2. Corticosteroid-loaded biodegradable nanoparticles for prevention of corneal allograft rejection in rats.

    PubMed

    Pan, Qing; Xu, Qingguo; Boylan, Nicholas J; Lamb, Nicholas W; Emmert, David G; Yang, Jeh-Chang; Tang, Li; Heflin, Tom; Alwadani, Saeed; Eberhart, Charles G; Stark, Walter J; Hanes, Justin

    2015-03-10

    Immunologic graft rejection is one of the main causes of short and long-term graft failure in corneal transplantation. Steroids are the most commonly used immunosuppressive agents for postoperative management and prevention of corneal graft rejection. However, steroids delivered in eye drops are rapidly cleared from the surface of the eye, so the required frequency of dosing for corneal graft rejection management can be as high as once every 2h. Additionally, these eye drops are often prescribed for daily use for 1 year or longer, which can result in poor patient compliance and steroid-related side effects. Here, we report a biodegradable nanoparticle system composed of Generally Regarded as Safe (GRAS) materials that can provide sustained release of corticosteroids to prevent corneal graft rejection following subconjunctival injection provided initially during transplant surgery. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing dexamethasone sodium phosphate (DSP) exhibited a size of 200 nm, 8 wt.% drug loading, and sustained drug release over 15 days in vitro under sink conditions. DSP-loaded nanoparticles provided sustained ocular drug levels for at least 7 days after subconjunctival administration in rats, and prevented corneal allograft rejection over the entire 9-week study when administered weekly. In contrast, control treatment groups that received weekly injections of either placebo nanoparticles, saline, or DSP in solution demonstrated corneal graft rejection accompanied by severe corneal edema, neovascularization and opacity that occurred in ≤ 4 weeks. Local controlled release of corticosteroids may reduce the rate of corneal graft rejection, perhaps especially in the days immediately following surgery when risk of rejection is highest and when typical steroid eye drop administration requirements are particularly onerous. PMID:25576786

  3. Urinary Cell mRNA Profiles and Differential Diagnosis of Acute Kidney Graft Dysfunction

    PubMed Central

    Matignon, Marie; Ding, Ruchuang; Dadhania, Darshana M.; Mueller, Franco B.; Hartono, Choli; Snopkowski, Catherine; Li, Carol; Lee, John R.; Sjoberg, Daniel; Seshan, Surya V.; Sharma, Vijay K.; Yang, Hua; Nour, Bakr; Vickers, Andrew J.; Suthanthiran, Manikkam

    2014-01-01

    Noninvasive tests to differentiate the basis for acute dysfunction of the kidney allograft are preferable to invasive allograft biopsies. We measured absolute levels of 26 prespecified mRNAs in urine samples collected from kidney graft recipients at the time of for-cause biopsy for acute allograft dysfunction and investigated whether differential diagnosis of acute graft dysfunction is feasible using urinary cell mRNA profiles. We profiled 52 urine samples from 52 patients with biopsy specimens indicating acute rejection (26 acute T cell–mediated rejection and 26 acute antibody-mediated rejection) and 32 urine samples from 32 patients with acute tubular injury without acute rejection. A stepwise quadratic discriminant analysis of mRNA measures identified a linear combination of mRNAs for CD3ε, CD105, TLR4, CD14, complement factor B, and vimentin that distinguishes acute rejection from acute tubular injury; 10-fold cross-validation of the six-gene signature yielded an estimate of the area under the curve of 0.92 (95% confidence interval, 0.86 to 0.98). In a decision analysis, the six-gene signature yielded the highest net benefit across a range of reasonable threshold probabilities for biopsy. Next, among patients diagnosed with acute rejection, a similar statistical approach identified a linear combination of mRNAs for CD3ε, CD105, CD14, CD46, and 18S rRNA that distinguishes T cell–mediated rejection from antibody-mediated rejection, with a cross-validated estimate of the area under the curve of 0.81 (95% confidence interval, 0.68 to 0.93). Incorporation of these urinary cell mRNA signatures in clinical decisions may reduce the number of biopsies in patients with acute dysfunction of the kidney allograft. PMID:24610929

  4. Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells.

    PubMed

    Holland, Tai C; Killilea, David W; Shenvi, Swapna V; King, Janet C

    2015-12-01

    A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells. PMID:26420239

  5. Adolescent social rejection alters pain processing in a CB1 receptor dependent manner.

    PubMed

    Schneider, Peggy; Pätz, Monique; Spanagel, Rainer; Schneider, Miriam

    2016-07-01

    Experiences of social rejection represent a major source of distress and in particular peer rejection during adolescence has been implicated in various psychiatric disorders. Moreover, experimentally induced acute social rejection alters pain perception in humans, implicating overlapping neurocircuits for social and physical pains. We recently demonstrated that rearing of adolescent Wistar rats with inadequate, less playful play partners (Fischer 344) persistently decreases pain sensitivity, although the detailed mechanisms mediating the aversiveness during the social encounter remained unsettled. With the present study we examined the behavioral performance during acute interaction of female adolescent Wistar rats with either age-matched same-strain partners or rats from the Fischer 344 strain. We here identify the low responsiveness upon playful attacks, which appears to be characteristic for social play in the Fischer 344 strain, as one of the main aversive components for adolescent Wistar animals during cross-strain encounters, which subsequently diminishes thermal pain reactivity. A detailed behavioral analysis further revealed increased ultrasonic vocalization at 50kHz and an increased frequency of playful attacks for adolescent Wistar animals paired with a Fischer 344 rat compared to same-strain control pairs. Finally, an acute injection of a subthreshold dose of the cannabinoid type 1 receptor inverse agonist/antagonist SR141716 before the social encounter abolished enhanced play-soliciting behavior in Wistar/Fischer 344 pairs as well as the behavioral consequences of the rejection experience in adolescent Wistar rats, further emphasizing an important modulatory role of the endocannabinoid system in mediating the effects of social behavior and social pain. PMID:27157075

  6. Long-term efficacy of atorvastatin in allograft rejection following renal transplantation: A randomized clinical trial.

    PubMed

    Amirzargar, Mohammad A; Hosseini, Arsha Tafreshi; Gholiaf, Mahmood; Dadras, Farahnaz; Khoshjoo, Farhad

    2015-09-01

    Statins are a class of drug that can efficiently reduce the level of low-density lipoprotein (LDL) as well as increase the LDL receptors. Several non-lipid-lowering effects of this type of drug have been described. It is reported that they have an influence in preventing graft rejection, especially of the acute type. In this study, patients with end-stage renal disease and candidates for kidney transplantation were divided into two groups. Group A (intervention group) received atorvastatin for two weeks prior to their transplant surgery while group B (control group) received placebo. The lipid profile was tested (triglycerides, cholesterol, LDL) in all patients two weeks before the transplantation. After transplantation, drug use was stopped. We also checked the LDL serum levels in patients with raised lipid levels (LDL >100) every two weeks. After this period, the serum lipid levels were checked monthly up to six months. Hyperlipidemia, when present, was controlled by fibrates. Concerning the rejection episodes, there was no significant difference between the two groups. In group A (13 men and nine women), three (14.3%) cases of rejection were observed whereas four (21.3%) cases of rejection were seen in group B (11 men and 10 women) (P = 0.5). Within group A, five (22.7%) cases of delayed graft function were found while four (19%) similar cases were observed in group B (P = 0.7). There was no statistically significant difference concerning delayed graft function between the two groups. Despite all the mechanisms attributed to the probable anti-rejection properties of statins, we found no significant correlation with the administration of these drugs before transplantation and the protection against graft rejection episodes. PMID:26354567

  7. Rejection Sensitivity Moderates the Impact of Rejection on Self-Concept Clarity

    PubMed Central

    Ayduk, Özlem; Gyurak, Anett; Luerssen, Anna

    2014-01-01

    Self-concept clarity (SCC) refers to the extent to which self-knowledge is clearly and confidently defined, internally consistent, and temporally stable. Research shows that SCC can be undermined by failures in valued goal domains. Because preventing rejection is an important self-relevant goal for people high in rejection sensitivity (RS), it is hypothesized here that failures to attain this goal would cause them to experience diminished SCC. Study 1, an experimental study, showed that high-RS people’s SCC was undermined following rejection but not following an aversive experience unrelated to rejection. Study 2, a daily diary study of couples in relationships, used occurrence of partner conflicts to operationalize rejection. Replicating the findings in Study 1, having a conflict on any given diary day predicted a greater reduction in the SCC of high- compared to low-RS people on the following day. The implications for understanding the conditions under which rejection negatively affects the self-concept are discussed. PMID:19713567

  8. Implementation and Rejection of Industrial Steam System Energy Efficiency Measures

    SciTech Connect

    Therkelesen, Peter; McKane, Aimee

    2013-05-01

    Steam systems consume approximately one third of energy applied at U.S. industrial facilities. To reduce energy consumption, steam system energy assessments have been conducted on a wide range of industry types over the course of five years through the Energy Savings Assessment (ESA) program administered by the U.S. Department of Energy (U.S. DOE). ESA energy assessments result in energy efficiency measure recommendations that are given potential energy and energy cost savings and potential implementation cost values. Saving and cost metrics that measure the impact recommended measures will have at facilities, described as percentages of facility baseline energy and energy cost, are developed from ESA data and used in analyses. Developed savings and cost metrics are examined along with implementation and rejection rates of recommended steam system energy efficiency measures. Based on analyses, implementation of steam system energy efficiency measures is driven primarily by cost metrics: payback period and measure implementation cost as a percentage of facility baseline energy cost (implementation cost percentage). Stated reasons for rejecting recommended measures are primarily based upon economic concerns. Additionally, implementation rates of measures are not only functions of savings and cost metrics, but time as well.

  9. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome

    PubMed Central

    Patel, Bhakti K.; Wolfe, Krysta S.; Pohlman, Anne S.; Hall, Jesse B.; Kress, John P.

    2016-01-01

    IMPORTANCE Noninvasive ventilation (NIV) with a face mask is relatively ineffective at preventing endotracheal intubation in patients with acute respiratory distress syndrome (ARDS). Delivery of NIV with a helmet may be a superior strategy for these patients. OBJECTIVE To determine whether NIV delivered by helmet improves intubation rate among patients with ARDS. DESIGN, SETTING, AND PARTICIPANTS Single-center randomized clinical trial of 83 patients with ARDS requiring NIV delivered by face mask for at least 8 hours while in the medical intensive care unit at the University of Chicago between October 3, 2012, through September 21, 2015. INTERVENTIONS Patients were randomly assigned to continue face mask NIV or switch to a helmet for NIV support for a planned enrollment of 206 patients (103 patients per group). The helmet is a transparent hood that covers the entire head of the patient and has a rubber collar neck seal. Early trial termination resulted in 44 patients randomized to the helmet group and 39 to the face mask group. MAIN OUTCOMES AND MEASURES The primary outcome was the proportion of patients who required endotracheal intubation. Secondary outcomes included 28-day invasive ventilator–free days (ie, days alive without mechanical ventilation), duration of ICU and hospital length of stay, and hospital and 90-day mortality. RESULTS Eighty-three patients (45% women; median age, 59 years; median Acute Physiology and Chronic Health Evaluation [APACHE] II score, 26) were included in the analysis after the trial was stopped early based on predefined criteria for efficacy. The intubation rate was 61.5% (n = 24) for the face mask group and 18.2% (n = 8) for the helmet group (absolute difference, −43.3%; 95% CI, −62.4%to −24.3%; P < .001). The number of ventilator-free days was significantly higher in the helmet group (28 vs 12.5, P < .001). At 90 days, 15 patients (34.1%) in the helmet group died compared with 22 patients (56.4%) in the face mask group

  10. Ebola Virus and Severe Acute Respiratory Syndrome Coronavirus Display Late Cell Entry Kinetics: Evidence that Transport to NPC1+ Endolysosomes Is a Rate-Defining Step

    PubMed Central

    Mingo, Rebecca M.; Simmons, James A.; Shoemaker, Charles J.; Nelson, Elizabeth A.; Schornberg, Kathryn L.; D'Souza, Ryan S.; Casanova, James E.

    2014-01-01

    ABSTRACT Ebola virus (EBOV) causes hemorrhagic fevers with high mortality rates. During cellular entry, the virus is internalized by macropinocytosis and trafficked through endosomes until fusion between the viral and an endosomal membrane is triggered, releasing the RNA genome into the cytoplasm. We found that while macropinocytotic uptake of filamentous EBOV viruslike particles (VLPs) expressing the EBOV glycoprotein (GP) occurs relatively quickly, VLPs only begin to enter the cytoplasm after a 30-min lag, considerably later than particles bearing the influenza hemagglutinin or GP from lymphocytic choriomeningitis virus, which enter through late endosomes (LE). For EBOV, the long lag is not due to the large size or unusual shape of EBOV filaments, the need to prime EBOV GP to the 19-kDa receptor-binding species, or a need for unusually low endosomal pH. In contrast, since we observed that EBOV entry occurs upon arrival in Niemann-Pick C1 (NPC1)-positive endolysosomes (LE/Lys), we propose that trafficking to LE/Lys is a key rate-defining step. Additional experiments revealed, unexpectedly, that severe acute respiratory syndrome (SARS) S-mediated entry also begins only after a 30-min lag. Furthermore, although SARS does not require NPC1 for entry, SARS entry also begins after colocalization with NPC1. Since the only endosomal requirement for SARS entry is cathepsin L activity, we tested and provide evidence that NPC1+ LE/Lys have higher cathepsin L activity than LE, with no detectable activity in earlier endosomes. Our findings suggest that both EBOV and SARS traffic deep into the endocytic pathway for entry and that they do so to access higher cathepsin activity. IMPORTANCE Ebola virus is a hemorrhagic fever virus that causes high fatality rates when it spreads from zoonotic vectors into the human population. Infection by severe acute respiratory syndrome coronavirus (SARS-CoV) causes severe respiratory distress in infected patients. A devastating outbreak of EBOV

  11. Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: the effect of dose rate on acute respiratory tract inflammation

    PubMed Central

    2014-01-01

    Background The increased production of nanomaterials has caused a corresponding increase in concern about human exposures in consumer and occupational settings. Studies in rodents have evaluated dose–response relationships following respiratory tract (RT) delivery of nanoparticles (NPs) in order to identify potential hazards. However, these studies often use bolus methods that deliver NPs at high dose rates that do not reflect real world exposures and do not measure the actual deposited dose of NPs. We hypothesize that the delivered dose rate is a key determinant of the inflammatory response in the RT when the deposited dose is constant. Methods F-344 rats were exposed to the same deposited doses of titanium dioxide (TiO2) NPs by single or repeated high dose rate intratracheal instillation or low dose rate whole body aerosol inhalation. Controls were exposed to saline or filtered air. Bronchoalveolar lavage fluid (BALF) neutrophils, biochemical parameters and inflammatory mediator release were quantified 4, 8, and 24 hr and 7 days after exposure. Results Although the initial lung burdens of TiO2 were the same between the two methods, instillation resulted in greater short term retention than inhalation. There was a statistically significant increase in BALF neutrophils at 4, 8 and 24 hr after the single high dose TiO2 instillation compared to saline controls and to TiO2 inhalation, whereas TiO2 inhalation resulted in a modest, yet significant, increase in BALF neutrophils 24 hr after exposure. The acute inflammatory response following instillation was driven primarily by monocyte chemoattractant protein-1 and macrophage inflammatory protein-2, mainly within the lung. Increases in heme oxygenase-1 in the lung were also higher following instillation than inhalation. TiO2 inhalation resulted in few time dependent changes in the inflammatory mediator release. The single low dose and repeated exposure scenarios had similar BALF cellular and mediator response trends

  12. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  13. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  14. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  15. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  16. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT... Rejection of bids....

  17. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN... 2414.404 Rejection of bids....

  18. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN... 2414.404 Rejection of bids....

  19. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN... 2414.404 Rejection of bids....

  20. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN... 2414.404 Rejection of bids....

  1. Bortezomib in late antibody-mediated kidney transplant rejection (BORTEJECT Study): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Despite major advances in transplant medicine, improvements in long-term kidney allograft survival have not been commensurate with those observed shortly after transplantation. The formation of donor-specific antibodies (DSA) and ongoing antibody-mediated rejection (AMR) processes may critically contribute to late graft loss. However, appropriate treatment for late AMR has not yet been defined. There is accumulating evidence that the proteasome inhibitor bortezomib may substantially affect the function and integrity of alloantibody-secreting plasma cells. The impact of this agent on the course of late AMR has not so far been systematically investigated. Methods/design The BORTEJECT Study is a randomized controlled trial designed to clarify the impact of intravenous bortezomib on the course of late AMR. In this single-center study (nephrological outpatient service, Medical University Vienna) we plan an initial cross-sectional DSA screening of 1,000 kidney transplant recipients (functioning graft at ≥180 days; estimated glomerular filtration rate (eGFR) >20 ml/minute/1.73 m2). DSA-positive recipients will be subjected to kidney allograft biopsy to detect morphological features consistent with AMR. Forty-four patients with biopsy-proven AMR will then be included in a double-blind placebo-controlled intervention trial (1:1 randomization stratified for eGFR and the presence of T-cell-mediated rejection). Patients in the active group will receive two cycles of bortezomib (4 × 1.3 mg/m2 over 2 weeks; 3-month interval between cycles). The primary end point will be the course of eGFR over 24 months (intention-to-treat analysis). The sample size was calculated according to the assumption of a 5 ml/minute/1.73 m2 difference in eGFR slope (per year) between the two groups (alpha: 0.05; power: 0.8). Secondary endpoints will be DSA levels, protein excretion, measured glomerular filtration rate, transplant and patient survival, and the development of

  2. Mechanisms of allograft rejection of corneal endothelium

    SciTech Connect

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

    1982-07-01

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

  3. A new rejection of moral expertise.

    PubMed

    Cowley, Christopher

    2005-01-01

    There seem to be two clearly-defined camps in the debate over the problem of moral expertise. On the one hand are the "Professionals", who reject the possibility entirely, usually because of the intractable diversity of ethical beliefs. On the other hand are the "Ethicists", who criticise the Professionals for merely stipulating science as the most appropriate paradigm for discussions of expertise. While the subject matter and methodology of good ethical thinking is certainly different from that of good clinical thinking, they argue, this is no reason for rejecting the possibility of a distinctive kind of expertise in ethics, usually based on the idea of good justification. I want to argue that both are incorrect, partly because of the reasons given by one group against the other, but more importantly because both neglect what is most distinctive about ethics: that it is personal in a very specific way, without collapsing into relativism. PMID:16283489

  4. Acute effect of alginate-based preload on satiety feelings, energy intake, and gastric emptying rate in healthy subjects.

    PubMed

    Georg Jensen, Morten; Kristensen, Mette; Belza, Anita; Knudsen, Jes C; Astrup, Arne

    2012-09-01

    Viscous dietary fibers such as sodium alginate extracted from brown seaweed have received much attention lately for their potential role in energy regulation through the inhibition of energy intake and increase of satiety feelings. The aim of our study was to investigate the effect on postprandial satiety feelings, energy intake, and gastric emptying rate (GER), by the paracetamol method, of two different volumes of an alginate-based preload in normal-weight subjects. In a four-way placebo-controlled, double-blind, crossover trial, 20 subjects (age: 25.9 ± 3.4 years; BMI: 23.5 ± 1.7 kg/m(2)) were randomly assigned to receive a 3% preload concentration of either low volume (LV; 9.9 g alginate in 330 ml) or high volume (HV; 15.0 g alginate in 500 ml) alginate-based beverage, or an iso-volume placebo beverage. The preloads were ingested 30 min before a fixed breakfast and again before an ad libitum lunch. Consumption of LV-alginate preload induced a significantly lower (8.0%) energy intake than the placebo beverage (P = 0.040) at the following lunch meal, without differences in satiety feelings or paracetamol concentrations. The HV alginate significantly increased satiety feelings (P = 0.038), reduced hunger (P = 0.042) and the feeling of prospective food consumption (P = 0.027), and reduced area under the curve (iAUC) paracetamol concentrations compared to the placebo (P = 0.05). However, only a 5.5% reduction in energy intake was observed for HV alginate (P = 0.20). Although they are somewhat contradictory, our results suggest that alginate consumption does affect satiety feelings and energy intake. However, further investigation on the volume of alginate administered is needed before inferring that this fiber has a possible role in short-term energy regulation. PMID:21779093

  5. Optical communication noise rejection using corelated photons

    NASA Technical Reports Server (NTRS)

    Jackson, D.; Hockney, G. M.; Dowling, J. P.

    2002-01-01

    This paper describes a completely new way to perform noise rejection using photons correlated through quantum entanglement to improve an optical communications link in the presence of uncorrelated noise. In particular, a detailed analysis is made of the case where a classical link would be saturated by an intense background, such as when a satellite is in front of the sun, and identifies where the quantum correlating system has superior performance.

  6. Funding for NSF underground laboratory is rejected

    SciTech Connect

    Kramer, David

    2011-02-15

    The Deep Underground Science and Engineering Laboratory (DUSEL), which proponents hope could provide a niche for the US particle-physics community, faces a shutdown as early as 1 April; the National Science Board (NSB) has rejected $19 million in funding needed to keep the project going through the fall of this year. The lab is housed in a disused gold mine in South Dakota's Black Hills.

  7. Active disturbance rejection controller for chemical reactor

    SciTech Connect

    Both, Roxana; Dulf, Eva H.; Muresan, Cristina I.

    2015-03-10

    In the petrochemical industry, the synthesis of 2 ethyl-hexanol-oxo-alcohols (plasticizers alcohol) is of high importance, being achieved through hydrogenation of 2 ethyl-hexenal inside catalytic trickle bed three-phase reactors. For this type of processes the use of advanced control strategies is suitable due to their nonlinear behavior and extreme sensitivity to load changes and other disturbances. Due to the complexity of the mathematical model an approach was to use a simple linear model of the process in combination with an advanced control algorithm which takes into account the model uncertainties, the disturbances and command signal limitations like robust control. However the resulting controller is complex, involving cost effective hardware. This paper proposes a simple integer-order control scheme using a linear model of the process, based on active disturbance rejection method. By treating the model dynamics as a common disturbance and actively rejecting it, active disturbance rejection control (ADRC) can achieve the desired response. Simulation results are provided to demonstrate the effectiveness of the proposed method.

  8. Current and future challenges in therapy for antibody-mediated rejection.

    PubMed

    Nair, Nandini; Ball, Timothy; Uber, Patricia A; Mehra, Mandeep R

    2011-06-01

    Antibody-mediated rejection (AMR) continues to present a challenge for the survival of the cardiac allograft. AMR appears to be on the rise, likely secondary to changing trends in clinical practice, including selection of patients for transplantation on mechanical circulatory support and development of more effective combinations of immunosuppressive drugs against acute cellular rejection. Most current strategies are aimed at treating acute AMR, but the treatment of chronic AMR is still not well defined. Clinically, AMR can often be more severe than cellular rejection and more difficult to treat, often not responding to typical protocols of increased immunosuppression. Complex steps involved in the antibody response allows for several potential targets for therapeutic intervention, including suppression of T and B cells, elimination of circulating antibodies, and inhibition of residual antibodies. Existing evidence suggests a multiregimen approach is the best option. Sustenance of accommodation and induction of tolerance could be viewed as viable options if adequate immune surveillance can be achieved in this setting. This review discusses the challenges in treating AMR and provides a critical analysis of current and possible future therapies. PMID:21474341

  9. Effect of Heat Rejection Conditions on Cryocooler Operational Stability

    NASA Technical Reports Server (NTRS)

    Ross, R. G., Jr.; Johnson, D. L.

    1997-01-01

    It is well known that cryocooler thermal efficiency is a strong function of heat rejection temperature, roughly following the dependency described by carnot. An equally important and generally overlooked implication of cryocooler heat-rejection thermodynamics is the effect of the heat rejection temparature control mode on cyrocooler performance and operational stability.

  10. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 8 2014-10-01 2014-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  11. 7 CFR 56.24 - Rejection of application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Rejection of application. 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application. (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  12. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2013-01-01 2013-01-01 false Approval or rejection. 1956.84 Section...

  13. 18 CFR 154.5 - Rejection of filings.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Rejection of filings. 154.5 Section 154.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Conditions § 154.5 Rejection of filings. A filing that fails to comply with this part may be rejected by...

  14. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 8 2013-10-01 2013-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  15. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  16. 18 CFR 154.5 - Rejection of filings.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Rejection of filings. 154.5 Section 154.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Conditions § 154.5 Rejection of filings. A filing that fails to comply with this part may be rejected by...

  17. 18 CFR 154.5 - Rejection of filings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Rejection of filings. 154.5 Section 154.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Conditions § 154.5 Rejection of filings. A filing that fails to comply with this part may be rejected by...

  18. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  19. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  20. 18 CFR 50.8 - Acceptance/rejection of applications.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Acceptance/rejection of... ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be... chapter. This rejection is without prejudice to an applicant's refiling a complete application....

  1. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  2. 18 CFR 154.5 - Rejection of filings.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Rejection of filings. 154.5 Section 154.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Conditions § 154.5 Rejection of filings. A filing that fails to comply with this part may be rejected by...

  3. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  4. 7 CFR 56.24 - Rejection of application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Rejection of application. 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application. (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  5. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  6. 37 CFR 1.113 - Final rejection or action.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Final rejection or action. 1... Applicant and Further Consideration § 1.113 Final rejection or action. (a) On the second or any subsequent examination or consideration by the examiner the rejection or other action may be made final,...

  7. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2014-01-01 2014-01-01 false Approval or rejection. 1956.84 Section...

  8. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  9. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  10. 37 CFR 1.113 - Final rejection or action.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Final rejection or action. 1... Applicant and Further Consideration § 1.113 Final rejection or action. (a) On the second or any subsequent examination or consideration by the examiner the rejection or other action may be made final,...

  11. 18 CFR 50.8 - Acceptance/rejection of applications.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Acceptance/rejection of... ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be... chapter. This rejection is without prejudice to an applicant's refiling a complete application....

  12. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 8 2012-10-01 2012-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  13. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  14. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 8 2011-10-01 2011-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  15. When Is Peer Rejection Justifiable? Children's Understanding across Two Cultures

    ERIC Educational Resources Information Center

    Park, Yoonjung; Killen, Melanie

    2010-01-01

    This study investigated how Korean (N = 397) and U.S. (N = 333) children and adolescents (10 and 13 years of age) evaluated personality (aggression, shyness) and group (gender, nationality) characteristics as a basis for peer rejection in three contexts (friendship rejection, group exclusion, victimization). Overall, peer rejection based on "group…

  16. 18 CFR 50.8 - Acceptance/rejection of applications.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Acceptance/rejection of... ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be... chapter. This rejection is without prejudice to an applicant's refiling a complete application....

  17. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  18. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  19. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2011-01-01 2011-01-01 false Approval or rejection. 1956.84 Section...

  20. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  1. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2012-01-01 2012-01-01 false Approval or rejection. 1956.84 Section...

  2. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  3. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  4. 7 CFR 56.24 - Rejection of application.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Rejection of application. 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application. (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  5. 7 CFR 56.24 - Rejection of application

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Rejection of application 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  6. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  7. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2010-01-01 2009-01-01 true Approval or rejection. 1956.84 Section...

  8. 7 CFR 56.24 - Rejection of application

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rejection of application 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  9. 37 CFR 1.113 - Final rejection or action.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Final rejection or action. 1... Applicant and Further Consideration § 1.113 Final rejection or action. (a) On the second or any subsequent examination or consideration by the examiner the rejection or other action may be made final,...

  10. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  11. Children's Coping with "In Vivo" Peer Rejection: An Experimental Investigation

    ERIC Educational Resources Information Center

    Reijntjes, Albert; Stegge, Hedy; Terwogt, Mark Meerum; Kamphuis, Jan Henk; Telch, Michael J.

    2006-01-01

    We examined children's behavioral coping in response to an "in vivo" peer rejection manipulation. Participants (N = 186) ranging between 10 and 13 years of age, played a computer game based on the television show "Survivor" and were randomized to either peer rejection (i.e., being voted out of the game) or non-rejection control. During a five-min.…

  12. Paying to belong: when does rejection trigger ingratiation?

    PubMed

    Romero-Canyas, Rainer; Downey, Geraldine; Reddy, Kavita S; Rodriguez, Sylvia; Cavanaugh, Timothy J; Pelayo, Rosemary

    2010-11-01

    Societies and social scientists have long held the belief that exclusion induces ingratiation and conformity, an idea in contradiction to robust empirical evidence linking rejection with hostility and aggression. The classic literatures on ingratiation and conformity help resolve this contradiction by identifying circumstances under which rejection may trigger efforts to ingratiate. Jointly, findings from these literatures suggest that when people are given an opportunity to impress their rejecters, ingratiation is likely after rejection experiences that are harsh and that occur in important situations that threaten the individual's self-definition. Four studies tested the hypothesis that people high in rejection sensitivity and therefore dispositionally concerned about rejection will utilize opportunities to ingratiate after harsh rejection in situations that are self-defining. In 3 studies of situations that are particularly self-defining for men, rejection predicted ingratiation among men (but not women) who were high in rejection sensitivity. In a 4th study, harsh rejection in a situation particularly self-defining for women predicted ingratiation among highly rejection-sensitive women (but not men). These findings help identify the specific circumstances under which people are willing to act in socially desirable ways toward those who have rejected them harshly. PMID:20649367

  13. Paying To Belong: When Does Rejection Trigger Ingratiation?

    PubMed Central

    Romero-Canyas, Rainer; Downey, Geraldine; Reddy, Kavita S.; Rodriguez, Sylvia; Cavanaugh, Timothy J.; Pelayo, Rosemary

    2010-01-01

    Societies and social scientists have long held the belief that exclusion induces ingratiation and conformity, an idea in contradiction with robust empirical evidence linking rejection with hostility and aggression. The classic literatures on ingratiation and conformity help resolve this contradiction by identifying circumstances under which rejection may trigger efforts to ingratiate. Jointly, findings from these literatures suggest that when people are given an opportunity to impress their rejecters, ingratiation is likely after rejection experiences that are harsh and that occur in important situations that threaten the individual’s self-definition. Four studies tested the hypothesis that people high in rejection sensitivity, and therefore dispositionally concerned about rejection, will utilize opportunities to ingratiate after harsh rejection in situations that are self-defining. In three studies of situations that are particularly self-defining for men, rejection predicted ingratiation among men (but not women) who were high in rejection sensitivity. In a fourth study, harsh rejection in a situation particularly self-defining for women predicted ingratiation among highly rejection-sensitive women (but not men). These findings help identify the specific circumstances under which people are willing to act in socially desirable ways toward those who have rejected them harshly. PMID:20649367

  14. 48 CFR 19.505 - Rejecting Small Business Administration recommendations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Rejecting Small Business... REGULATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 19.505 Rejecting Small Business Administration recommendations. (a) If the contracting officer rejects a...

  15. 48 CFR 19.505 - Rejecting Small Business Administration recommendations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rejecting Small Business... REGULATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 19.505 Rejecting Small Business Administration recommendations. (a) If the contracting officer rejects a...

  16. Anti-Leukocyte Function-Associated Antigen 1 Therapy in a Nonhuman Primate Renal Transplant Model of Costimulation Blockade-Resistant Rejection.

    PubMed

    Anderson, D J; Lo, D J; Leopardi, F; Song, M; Turgeon, N A; Strobert, E A; Jenkins, J B; Wang, R; Reimann, K A; Larsen, C P; Kirk, A D

    2016-05-01

    Costimulation blockade with the fusion protein belatacept provides a desirable side effect profile and improvement in renal function compared with calcineurin inhibition in renal transplantation. This comes at the cost of increased rates of early acute rejection. Blockade of the integrin molecule leukocyte function-associated antigen 1 (LFA-1) has been shown to be an effective adjuvant to costimulation blockade in a rigorous nonhuman primate (NHP) model of islet transplantation; therefore, we sought to test this combination in an NHP renal transplant model. Rhesus macaques received belatacept maintenance therapy with or without the addition of LFA-1 blockade, which was achieved using a murine-derived LFA-1-specific antibody TS1/22. Additional experiments were performed using chimeric rhesus IgG1 (TS1/22R1) or IgG4 (TS1/22R4) variants, each engineered to limit antibody clearance. Despite evidence of proper binding to the target molecule and impaired cellular egress from the intravascular space indicative of a therapeutic effect similar to prior islet studies, LFA-1 blockade failed to significantly prolong graft survival. Furthermore, evidence of impaired protective immunity against cytomegalovirus was observed. These data highlight the difficulties in translating treatment regimens between organ models and suggest that the primarily vascularized renal model is more robust with regard to belatacept-resistant rejection than the islet model. PMID:26602755

  17. Salt rejection and water transport through boron nitride nanotubes.

    PubMed

    Hilder, Tamsyn A; Gordon, Daniel; Chung, Shin-Ho

    2009-10-01

    Nanotube-based water-purification devices have the potential to transform the field of desalination and demineralization through their ability to remove salts and heavy metals without significantly affecting the fast flow of water molecules. Boron nitride nanotubes have shown superior water flow properties compared to carbon nanotubes, and are thus expected to provide a more efficient water purification device. Using molecular dynamics simulations it is shown that a (5, 5) boron nitride nanotube embedded in a silicon nitride membrane can, in principle, obtain 100% salt rejection at concentrations as high as 1 M owing to a high energy barrier while still allowing water molecules to flow at a rate as high as 10.7 water molecules per nanosecond (or 0.9268 L m(-2) h(-1)). Furthermore, ions continue to be rejected under the influence of high hydrostatic pressures up to 612 MPa. When the nanotube radius is increased to 4.14 A the tube becomes cation-selective, and at 5.52 A the tube becomes anion-selective. PMID:19582727

  18. Heart rate variability changes at 2400 m altitude predicts acute mountain sickness on further ascent at 3000–4300 m altitudes

    PubMed Central

    Karinen, Heikki M.; Uusitalo, Arja; Vähä-Ypyä, Henri; Kähönen, Mika; Peltonen, Juha E.; Stein, Phyllis K.; Viik, Jari; Tikkanen, Heikki O.

    2012-01-01

    Objective: If the body fails to acclimatize at high altitude, acute mountain sickness (AMS) may result. For the early detection of AMS, changes in cardiac autonomic function measured by heart rate variability (HRV) may be more sensitive than clinical symptoms alone. The purpose of this study was to ascertain if the changes in HRV during ascent are related to AMS. Methods: We followed Lake Louise Score (LLS), arterial oxygen saturation at rest (R-SpO2) and exercise (Ex-SpO2) and HRV parameters daily in 36 different healthy climbers ascending from 2400 m to 6300 m altitudes during five different expeditions. Results: After an ascent to 2400 m, root mean square successive differences, high-frequency power (HF2 min) of HRV were 17–51% and Ex-SpO2 was 3% lower in those climbers who suffered from AMS at 3000 to 4300 m than in those only developing AMS later (≥5000 m) or not at all (all p < 0.01). At the altitude of 2400 m RMSSD2 min ≤ 30 ms and Ex-SpO2 ≤ 91% both had 92% sensitivity for AMS if ascent continued without extra acclimatization days. Conclusions: Changes in supine HRV parameters at 2400 m were related to AMS at 3000–4300 m Thus, analyses of HRV could offer potential markers for identifying the climbers at risk for AMS. PMID:22969727

  19. Association of ITPA Genotype with Event-Free Survival and Relapse Rates in Children with Acute Lymphoblastic Leukemia Undergoing Maintenance Therapy

    PubMed Central

    Smid, Alenka; Karas-Kuzelicki, Natasa; Milek, Miha; Jazbec, Janez; Mlinaric-Rascan, Irena

    2014-01-01

    Although the treatment of acute lymphoblastic leukemia (ALL) has improved significantly over recent decades, failure due to treatment-related toxicities and relapse of the disease still occur in about 20% of patients. This retrospective study included 308 pediatric ALL patients undergoing maintenance therapy and investigated the effects of genetic variants of enzymes involved in the 6-mercaptopurine (6-MP) metabolism and folate pathway on survival and relapse rates. The presence of at least one of the non-functional ITPA alleles (94C>A and/or IVS2+21A>C variant) was associated with longer event-free survival compared to patients with the wild-type ITPA genotype (p = 0.033). Furthermore, patients carrying at least one non-functional ITPA allele were shown to be at a lower risk of suffering early (p = 0.003) and/or bone marrow relapse (p = 0.017). In conclusion, the ITPA genotype may serve as a genetic marker for the improvement of risk stratification and therapy individualization for patients with ALL. PMID:25303517

  20. 18 CFR 35.5 - Rejection of material submitted for filing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... that fails to comply with this Part may be rejected by the Director of the Office of Energy Market... submitted for filing. 35.5 Section 35.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT FILING OF RATE SCHEDULES AND...