Sample records for sub-clinical acute rejection

  1. Acute rejection in vascularized composite allotransplantation.

    PubMed

    Fischer, Sebastian; Lian, Christine G; Kueckelhaus, Maximilian; Strom, Terry B; Edelman, Elazer R; Clark, Rachel A; Murphy, George F; Chandraker, Anil K; Riella, Leonardo V; Tullius, Stefan G; Pomahac, Bohdan

    2014-12-01

    Acute rejection is the most common complication after vascularized composite allotransplantation (VCA). This review provides a state-of-the-art analysis of prevention, diagnosis and treatment of acute rejection episodes and highlights recent findings with the potential to improve patient care and enhance understanding of the underlying biologic processes. Recent reports suggest that maintenance immunosuppression dose reduction and steroid withdrawal are realistic goals in VCA, despite the known high immunogenicity of the skin component. It appears that utilization of sentinel flaps, in-depth histological analyses and application of novel biomarkers have facilitated early diagnosis and characterization of acute rejection episodes, leading to timely institution of appropriate therapy. The successful management of the first highly sensitized face transplant recipient suggests the possibility of carefully considering these high-risk VCA candidates for transplantation. Acute rejection is higher in VCA than in any other organ in the field of transplantation, although most episodes are controlled by high-dose steroids and optimization of maintenance immunosuppression. Because of limitations in patient number and the duration of follow-up, the long-term safety and effectiveness of VCA remain unclear. Moreover, the tests currently used to diagnose acute rejection are of limited value. Better diagnostic tools and a better understanding of the immunologic events during acute rejection are therefore needed to improve diagnosis, treatment and outcomes of this life-changing restorative surgery.

  2. Detection of urinary biomarkers for early diagnosis of acute renal allograft rejection by proteomic analysis.

    PubMed

    Jia, Xiongfei; Gan, Chengjun; Xiao, Ke; He, Weifeng; Zhang, Tao; Huang, Cibing; Wu, Xiongfei; Luo, Gaoxing; Wang, Xiaojuan; Hu, Jie; Tan, Jiangling; Zhang, Xiaorong; Larsen, Peter Mose; Wu, Jun

    2009-06-01

    Acute allograft rejection has been recognized as a major impediment to improved success in renal transplantation. Timely detection and control of rejection are very important for the improvement in long-term renal allograft survival. Thus, biomarkers for early diagnosis of acute rejection are required urgently to clinical medication. This study seeks to search for such biomarker candidates by comparing patients' pre-treatment urinary protein profiling with their post-treatment urinary protein profiling. A total of 15 significantly and consistently down-regulated protein candidates were identified. Among them, alpha-1-antichymotrypsin precursor (AACT), tumor rejection antigen gp96 (GP96) and Zn-Alpha-2-Glycoprotein (ZAG) were selected for further analysis. The results indicated that Western Blot assay of AACT, GP96 and ZAG had advanced the diagnosis time of acute renal rejection by 3 days, compared with current standard clinical observation and laboratory examination. Furthermore, the double-blind detection revealed that the accuracy, sensitivity and specificity of the diagnosis of acute renal rejection of AACT, GP96 and ZAG were 66.67%/100%/60%, 83.33%/100%/80% and 66.67%/100%/60%, respectively, and 100%/100%/100% in combination. In conclusion, urinary protein AACT, GP96 and ZAG could be a set of potential biomarkers for early non-invasive diagnosis of the acute rejection after renal transplantation. Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Acute pulmonary allograft rejection. Mechanisms, diagnosis, and management.

    PubMed

    King-Biggs, M B

    1997-06-01

    Rejection is a common complication following lung transplantation, and can lead to considerable short- and long-term morbidity. As numbers and survival rates of lung transplant recipients increase, it is apparent that acute rejection can occur months or years after transplantation, and may be resistant to standard therapies. Mechanisms of acute rejection have been well studied in other solid organ transplant recipients, and are beginning to be addressed in the lung recipient. This article addresses some of the common issues of diagnosis and management of acute rejection which arise frequently during the care of lung transplant recipients.

  4. Role for urinary biomarkers in diagnosis of acute rejection in the transplanted kidney.

    PubMed

    Merhi, Basma; Bayliss, George; Gohh, Reginald Y

    2015-12-24

    Despite the introduction of potent immunosuppressive medications within recent decades, acute rejection still accounts for up to 12% of all graft losses, and is generally associated with an increased risk of late graft failure. Current detection of acute rejection relies on frequent monitoring of the serum creatinine followed by a diagnostic renal biopsy. This strategy is flawed since an alteration in the serum creatinine is a late clinical event and significant irreversible histologic damage has often already occurred. Furthermore, biopsies are invasive procedures that carry their own inherent risk. The discovery of non-invasive urinary biomarkers to help diagnose acute rejection has been the subject of a significant amount of investigation. We review the literature on urinary biomarkers here, focusing on specific markers perforin and granzyme B mRNAs, FOXP3 mRNA, CXCL9/CXCL10 and miRNAs. These and other biomarkers are not yet widely used in clinical settings, but our review of the literature suggests that biomarkers may correlate with biopsy findings and provide an important early indicator of rejection, allowing more rapid treatment and better graft survival.

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

    PubMed

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

    2009-12-01

    Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. In this prospective study,we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. Preoperative sCD30 levels of 3 groups were 96.2 -/+ 32.5, 80.2 -/+ 28.3, and 76.8 -/+ 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P < .001), while sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 -/+ 5.2, 22.1 -/+ 3.2, and 19.8 -/+ 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period.

  6. Role for urinary biomarkers in diagnosis of acute rejection in the transplanted kidney

    PubMed Central

    Merhi, Basma; Bayliss, George; Gohh, Reginald Y

    2015-01-01

    Despite the introduction of potent immunosuppressive medications within recent decades, acute rejection still accounts for up to 12% of all graft losses, and is generally associated with an increased risk of late graft failure. Current detection of acute rejection relies on frequent monitoring of the serum creatinine followed by a diagnostic renal biopsy. This strategy is flawed since an alteration in the serum creatinine is a late clinical event and significant irreversible histologic damage has often already occurred. Furthermore, biopsies are invasive procedures that carry their own inherent risk. The discovery of non-invasive urinary biomarkers to help diagnose acute rejection has been the subject of a significant amount of investigation. We review the literature on urinary biomarkers here, focusing on specific markers perforin and granzyme B mRNAs, FOXP3 mRNA, CXCL9/CXCL10 and miRNAs. These and other biomarkers are not yet widely used in clinical settings, but our review of the literature suggests that biomarkers may correlate with biopsy findings and provide an important early indicator of rejection, allowing more rapid treatment and better graft survival. PMID:26722652

  7. Ultrasound molecular imaging of acute cardiac transplantation rejection using nanobubbles targeted to T lymphocytes.

    PubMed

    Liu, Jinfeng; Chen, Yihan; Wang, Guohua; Lv, Qing; Yang, Yali; Wang, Jing; Zhang, Pingyu; Liu, Jie; Xie, Yu; Zhang, Li; Xie, Mingxing

    2018-04-01

    Clinical surveillance of acute heart transplantation rejection requires repeated invasive endomyocardial biopsies and noninvasive diagnostic techniques are desperately needed. It is acknowledged that T lymphocyte infiltration is the central process of acute rejection. We hypothesized that ultrasound molecular imaging with T lymphocyte-targeted nanobubbles could be used to detect acute rejection in heart transplantation. In this study, nanobubbles bearing anti-CD3 antibody (NB CD3 ) or isotype antibody (NB con ) were prepared and characterized. There was significant adhesion of NB CD3 to T lymphocytes compared with NB con in vitro. The signal intensity of the adherent NB CD3 was significantly higher than that of the NB con in allograft rats, but not significantly different in isograft rats. Furthermore, the signal intensity of NB CD3 in allograft rats was significantly higher than that in isograft rats, indicating more T lymphocyte infiltration in allograft rats compared with isograft rats. These results were further confirmed by immunohistochemistry examination, and the signal intensity of NB CD3 was positively correlated with the number of T lymphocytes in allograft rats. In summary, ultrasound molecular imaging with T lymphocyte-targeted nanobubbles can detect T lymphocyte infiltration in acute rejection and could be used as a noninvasive method in acute rejection detection after cardiac transplantation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    PubMed

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

    2013-01-01

    Soluble CD30 (sCD30) has been proposed as a promising noninvasive biomarker for clinical renal allograft rejection, but its diagnostic characteristics regarding detection of subclinical rejection have not been assessed. We investigated sCD30 in 146 consecutive kidney allograft recipients under tacrolimus-mycophenolate-based immunosuppression having 250 surveillance biopsies at 3 and 6 months as well as 52 indication biopsies within the first year post-transplant. Allograft histology results were classified as (i) acute Banff score zero or interstitial infiltrates only, (ii) tubulitis t1, (iii) tubulitis t2-3 and (iv) isolated vascular compartment inflammation. sCD30 correlated well with the extent of clinical (P < 0.0001), but not subclinical tubulointerstitial rejection (P = 0.06). To determine diagnostic characteristics of sCD30, histological groups were assigned to two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (tubulitis t1-3 and isolated vascular compartment inflammation). For clinical allograft inflammation, AUC was 0.87 (sensitivity 89%, specificity 79%; P = 0.0006); however, for subclinical inflammation, AUC was only 0.59 (sensitivity 50%, specificity 69%; P = 0.47). In conclusion, sCD30 correlated with clinical, but not subclinical renal allograft rejection limiting its clinical utility as a noninvasive rejection screening biomarker in patients with stable allograft function receiving tacrolimus-mycophenolate-based immunosuppression. © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation.

  9. Soluble CD30 does not predict late acute rejection or safe tapering of immunosuppression in renal transplantation.

    PubMed

    Valke, Lars L F G; van Cranenbroek, Bram; Hilbrands, Luuk B; Joosten, Irma

    2015-01-01

    Previous reports revealed the potential value of the soluble CD30 level (sCD30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection. In a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether sCD30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (TDS cohort: 24 rejectors and 44 non-rejecting controls). Also, in a second cohort of patients (n=22, rejectors n=11 and non-rejectors n=11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (RITS cohort), we examined whether sCD30 could predict the occurrence of late (>3months post-transplant) acute rejection episodes. sCD30 was measured by ELISA in serum taken before and at several time points after transplantation. Overall, in the TDS cohort sCD30 decreased after transplantation. No difference in sCD30 was observed between rejectors and non-rejecting controls at any of the time points measured. In addition, in the RITS cohort, sCD30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection. In two prospectively followed cohorts of renal transplant patients we found no association between sCD30 and the occurrence of either late acute rejection or acute rejection after reduction of immunosuppression. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Practice Patterns in the Treatment and Monitoring of Acute T Cell-Mediated Kidney Graft Rejection in Canada.

    PubMed

    Leblanc, Julie; Subrt, Peter; Paré, Michèle; Hartell, David; Sénécal, Lynne; Blydt-Hansen, Tom; Cardinal, Héloïse

    2018-01-01

    One of the goals of the Canadian National Transplant Research Program (CNTRP) is to develop novel therapies for acute rejection that could positively affect graft outcomes with greater efficacy or less toxicity. To develop innovative management strategies for kidney graft rejection, new modalities need to be compared with current clinical practices. However, there are no standardized practices concerning the management of acute T cell-mediated rejection (TCMR). To describe clinicians' practice patterns in the diagnosis, treatment, and monitoring of acute TCMR in Canada. Survey. Canadian transplant nephrologists and transplant surgeons involved in the management of acute TCMR. We developed an anonymous, web-based survey consisting of questions related to the diagnosis, treatment, and monitoring of TCMR. The survey was disseminated on 3 occasions between June and October 2016 through the Canadian Society of Transplantation (CST) kidney group electronic mailing list. Forty-seven respondents, mostly transplant nephrologists (97%), originating from at least 18 of the 25 Canadian centers offering adult or pediatric kidney transplantation, participated in the study. Surveillance biopsies were used by 28% of respondents to screen for kidney graft rejection. High-dose steroids were used by most of the respondents to treat clinical and subclinical Banff grade 1A and 1B rejections. Nine percent (95% confidence interval [CI]: 1-17) of practitioners used lymphocyte-depleting agents as the first-line approach for the treatment of Banff grade 1B acute rejection. Eighteen percent (95% CI: 7-29) and 36% (95% CI: 8-65) of respondents reported that they would not use high-dose steroids for treating clinical and subclinical borderline rejections, respectively. Seventy percent (95% CI: 54-83) of respondents answered that there was no indication to assess histological response to treatment independent of the change in kidney function. The limitations of this study are its limited sample

  11. The Australian National Sub-Acute and Non-Acute Patient casemix classification.

    PubMed

    Eagar, K

    1999-01-01

    The Australian National Sub-Acute and Non-Acute Patient (AN-SNAP) Version 1 casemix classification was completed in 1997. AN-SNAP is designed for the classification of sub-acute and non-acute care provided in both inpatient and ambulatory settings and is intended to be useful for both funding and clinical management purposes. The National Sub-Acute and Non-Acute Casemix Classification study has produced the first version of a national classification of sub-acute and non-acute care. Ongoing refinement (leading to Version 2) will be possible through further analysis of the existing data set in combination with analysis of the results of a carefully planned and phased implementation.

  12. 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. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  13. The role of innate immunity in acute allograft rejection after lung transplantation.

    PubMed

    Palmer, Scott M; Burch, Lauranell H; Davis, R Duane; Herczyk, Walter F; Howell, David N; Reinsmoen, Nancy L; Schwartz, David A

    2003-09-15

    Although innate immunity is crucial to pulmonary host defense and can initiate immune and inflammatory responses independent of adaptive immunity, it remains unstudied in the context of transplant rejection. To investigate the role of innate immunity in the development of allograft rejection, we assessed the impact of two functional polymorphisms in the toll-like receptor 4 (TLR4) associated with endotoxin hyporesponsiveness on the development of acute rejection after human lung transplantation. Patients and donors were screened for the TLR4 Asp299Gly and Thr399Ile polymorphisms by polymerase chain reaction using sequence-specific primers. The rate of acute rejection at 6 months was significantly reduced in recipients, but not in donors, with the Asp299Gly or Thr399Ile alleles as compared with wild type (29 vs. 56%, respectively, p = 0.05). This association was confirmed in Cox proportional hazards and multivariate logistic regression models. Our results suggest activation of innate immunity in lung transplant recipients through TLR4 contributes to the development acute rejection after lung transplantation. Therapies directed at inhibition of innate immune responses mediated by TLR4 may represent a novel and effective means to prevent acute rejection after lung transplantation.

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

    PubMed

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

    2006-06-01

    To evaluate the feasibility of serum sCD30 for prediction of acute graft rejection, we analyzed clinical data of 231 patients, whose serum levels of sCD30 were detected by ELISA before and after transplantation. They were divided into three groups: acute rejection group (AR, n = 49), uncomplicated course group (UC, n = 171) and delayed graft function group (DGF, n = 11). Preoperative sCD30 levels of three groups were 183 +/- 74, 177 +/- 82 and 168 +/- 53 U/ml, respectively (P = 0.82). Significant decrease of sCD30 was detected in three groups on day 5 and 10 post-transplantation respectively (52 +/- 30 and 9 +/- 5 U/ml respectively, P < 0.001). Compared with Group UC and DGF, patients of Group AR had higher sCD30 values on day 5 post-transplantation (92 +/- 27 U/ml vs. 41 +/- 20 U/ml and 48 +/- 18 U/ml, P < 0.001). However, sCD30 levels on day 10 post-transplantation were virtually similar in patients of three groups (P = 0.43). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 5 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 91.8%, sensitivity 87.1%). Measurement of soluble CD30 on day 5 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.

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

    PubMed

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

    2009-12-01

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

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

    PubMed Central

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

    2017-01-01

    Abstract Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long‐term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord‐derived mesenchymal stem cell (UC‐MSC) therapy in liver transplant patients with acute graft rejection. Twenty‐seven liver allograft recipients with acute rejection were randomly assigned into the UC‐MSC infusion group or the control group. Thirteen patients received one infusion of UC‐MSCs (1 × 106/kg body weight); one patient received multiple UC‐MSC infusions; 13 patients were used as controls. All enrolled patients received conventional immunosuppressive agents with follow‐up for 12 weeks after UC‐MSC infusions. No side effects occurred in treated patients. Four weeks after UC‐MSC infusions, alanine aminotransferase levels had decreased markedly and remained lower throughout the 12‐week follow‐up period. Importantly, allograft histology was improved after administration of UC‐MSCs. The percentage of regulatory T cells (Tregs) and the Treg/T helper 17 (Th17) cell ratio were significantly increased 4 weeks after infusions; in contrast, the percentage of Th17 cells showed a decreasing trend. In controls, the percentages of Tregs and Th17 cells and the Treg/Th17 ratio were statistically unchanged from the baseline measurements. Transforming growth factor beta 1 and prostaglandin E2 were increased significantly after UC‐MSC infusions; by contrast, there were no significant changes in controls. Our data suggest that UC‐MSC infusion for acute graft rejection following liver transplantation is feasible and may mediate a therapeutic immunosuppressive effect. Stem Cells Translational Medicine 2017;6:2053–2061 PMID:29178564

  17. Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection.

    PubMed

    Pelzl, Steffen; Opelz, Gerhard; Daniel, Volker; Wiesel, Manfred; Süsal, Caner

    2003-02-15

    Posttransplantation measurement of soluble CD30 (sCD30) may be useful for identifying kidney graft recipients at risk of impending graft rejection in the early posttransplantation period. We measured plasma sCD30 levels and evaluated the levels in relation to the diagnosis of rejection. Receiver operating characteristic curves demonstrated that on posttransplantation days 3 to 5, sCD30 allowed a differentiation of recipients who subsequently developed acute allograft rejection (n=25) from recipients with an uncomplicated course (n=20, P<0.0001) (area under the receiver operating characteristic curve 0.96, specificity 100%, sensitivity 88%) and recipients with acute tubular necrosis in the absence of rejection (n=11, P=0.001) (area under the receiver operating characteristic curve 0.85, specificity 91%, sensitivity 72%). sCD30 measured on posttransplantation days 3 to 5 offers a noninvasive means for differentiating patients with impending acute allograft rejection from patients with an uncomplicated course or with acute tubular necrosis.

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

    PubMed

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

    2015-02-01

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

  19. 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

  20. Acute cellular rejection with isolated v-lesions is not associated with more favorable outcomes than vascular rejection with more tubulointerstitial inflammations.

    PubMed

    Wu, K Y; Budde, K; Schmidt, D; Neumayer, H H; Rudolph, B

    2014-04-01

    The impact of isolated v-lesions on clinical outcome in biopsies with acute cellular rejection (ACR) is unclear. Two hundred and sixty-five biopsies showing the highest ACR severity for each patient were recruited and classified into four groups: (i) acute interstitial rejection (AIR) I with minimal tubulointerstitial inflammation (TI), (ii) AIR II with intensive TI, (iii) acute vascular rejection (AVR) I with minimal TI, and (iv) AVR II with intensive TI. The complete reversal rates of AIR I and AIR II groups were marginally higher than AVR I and AVR II groups (p = 0.16). At eight yr of transplantation, the death-censored graft survival (DCGS) rate of AIR I group (93.3%) was significantly higher compared with the AVR I (72.7%) or AVR II (72.9%) group. AVR I group had a similar DCGS rate with AVR II group (72.7% vs. 74.1%), whereas AVR with v1-lesion showed significantly higher graft survival (GS) rate than those with v2-lesion (70.2% vs. 45.5%). The t-lesion of AIR and v-lesion of AVR group were associated with graft loss. The extent of TI is non-specifically associated with graft loss in biopsies with AVR; the higher grade v-lesion predicts the lower complete reversal rate and poorer long-term graft survival. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology.

    PubMed

    Speck, Nicole E; Schuurmans, Macé M; Murer, Christian; Benden, Christian; Huber, Lars C

    2016-06-21

    Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

  2. The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation.

    PubMed

    Do Nguyen, Hung Thanh; Wong, Germaine; Chapman, Jeremy R; McDonald, Stephen P; Coates, Patrick T; Watson, Narelle; Russ, Graeme R; D'Orsogna, Lloyd; Lim, Wai Hon

    2016-12-01

    Epitope matching, which evaluates mismatched amino acids within antigen-antibody interaction sites (eplets), may better predict acute rejection than broad antigen matching alone. We aimed to determine the association between eplet mismatches and acute rejection in kidney transplant recipients. The association between eplet mismatches, broad antigen mismatches and acute rejection was assessed using adjusted Cox proportional hazard regression. Model discrimination for acute rejection was evaluated using the area under receiver operating characteristic curves. Of the 3,499 kidney transplant recipients from 2006 to 2011, the average (SD) number of broad antigen and eplet mismatches were 3.4 (1.7) and 22.8 (12.2), respectively. Compared with 0 to 2 eplet mismatches, the adjusted hazard ratio (HR) for acute rejection among those with 20 or greater eplet mismatches was 2.16 (95% confidence interval [CI], 1.33-3.52; P = 0.001). The adjusted area under the curve for broad antigen mismatches was 0.58 (95% CI, 0.56-0.61), similar to that for eplet mismatches (HR, 0.59; 95% CI, 0.56-0.61; P = 0.365). In recipients who were considered as low immunological risk (0-2 broad antigen HLA-ABDR mismatch), those with 20 or greater eplet mismatches experienced an increased risk of rejection compared to those with less than 20 mismatches (adjusted HR, 1.85; 95% CI, 1.11-3.08; P = 0.019). Increasing number of eplet mismatches is associated with acute rejection in kidney transplant recipients. Consideration of eplet HLA mismatches may improve risk stratification for acute rejection in a selected group of kidney transplant candidates.

  3. Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation.

    PubMed

    Stubendorff, Beatrice; Finke, Stephanie; Walter, Martina; Kniemeyer, Olaf; von Eggeling, Ferdinand; Gruschwitz, Torsten; Steiner, Thomas; Ott, Undine; Wolf, Gunter; Wunderlich, Heiko; Junker, Kerstin

    2014-12-01

    Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice. Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay. A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 μg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity. Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

  4. Two-Stage, In Silico Deconvolution of the Lymphocyte Compartment of the Peripheral Whole Blood Transcriptome in the Context of Acute Kidney Allograft Rejection

    PubMed Central

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

    2014-01-01

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

  5. Longitudinal Analysis of Whole Blood Transcriptomes to Explore Molecular Signatures Associated With Acute Renal Allograft Rejection

    PubMed Central

    Shin, Heesun; Günther, Oliver; Hollander, Zsuzsanna; Wilson-McManus, Janet E.; Ng, Raymond T.; Balshaw, Robert; Keown, Paul A.; McMaster, Robert; McManus, Bruce M.; Isbel, Nicole M.; Knoll, Greg; Tebbutt, Scott J.

    2014-01-01

    In this study, we explored a time course of peripheral whole blood transcriptomes from kidney transplantation patients who either experienced an acute rejection episode or did not in order to better delineate the immunological and biological processes measureable in blood leukocytes that are associated with acute renal allograft rejection. Using microarrays, we generated gene expression data from 24 acute rejectors and 24 nonrejectors. We filtered the data to obtain the most unambiguous and robustly expressing probe sets and selected a subset of patients with the clearest phenotype. We then performed a data-driven exploratory analysis using data reduction and differential gene expression analysis tools in order to reveal gene expression signatures associated with acute allograft rejection. Using a template-matching algorithm, we then expanded our analysis to include time course data, identifying genes whose expression is modulated leading up to acute rejection. We have identified molecular phenotypes associated with acute renal allograft rejection, including a significantly upregulated signature of neutrophil activation and accumulation following transplant surgery that is common to both acute rejectors and nonrejectors. Our analysis shows that this expression signature appears to stabilize over time in nonrejectors but persists in patients who go on to reject the transplanted organ. In addition, we describe an expression signature characteristic of lymphocyte activity and proliferation. This lymphocyte signature is significantly downregulated in both acute rejectors and nonrejectors following surgery; however, patients who go on to reject the organ show a persistent downregulation of this signature relative to the neutrophil signature. PMID:24526836

  6. [The relationship between acute rejection and expression of sCD30 for the patients after kidney transplantation].

    PubMed

    Yang, Jian-Lin; Hao, Hong-Jun; Qin, Bin; Bang, Ling-Qing; Zhang, Zhi-Hong; Xin, Dian-Qi; Guo, Ying-Lu; Na, Yan-Qun

    2005-03-16

    To study the relationship between the sCD30 and acute rejection. We tested the sCD30 level in serum for 58 cases with kidney transplantation before and the 7th day and 28th day after operation by ELISA. 31 healthy individual for control group, and simultaneously recorded the incidence of rejection after kidney transplantation. The results showed that there is an obviously relation before kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 4.843, P = 0.028, P < 0.05). There is a significantly relation at the 7th day after kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 7.201, P = 0.007, P < 0.01). There is no obviously relation at 28th day after kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 2.095, P = 0.148, P > 0.05). The results suggested that the expressions of sCD30 are related to acute rejection. We speculated that the expressions of sCD30 could play an important role in acute rejection.

  7. HILDA/LIF urinary excretion during acute kidney rejection.

    PubMed

    Taupin, J L; Morel, D; Moreau, J F; Gualde, N; Potaux, L; Bezian, J H

    1992-03-01

    Recently, a new lymphokine called HILDA (human interleukin for DA cells) has been described and cloned. This cytokine, initially described to be produced by alloreactive T lymphocyte clones grown from a rejected human kidney allograft, is identical to other factors termed D-factor, differentiation-inducing factor, differentiation inhibitory activity, hepatocyte-stimulating factor III, and leukemia inhibitory factor. HILDA/LIF induces various effects on neural, hemopoietic, embryonic cells as well as on bone remodeling and acute phase protein synthesis in hepatocyte. In this study we demonstrate the presence of HILDA/LIF in the urine but not in the serum of kidney graft recipients during acute rejection episodes, whereas this lymphokine was detectable neither in the serum nor in the urine of kidney transplanted patients with stable renal function. These data reinforce the notion of a possible role for this lymphokine in the inflammatory and/or the immune response.

  8. Re-Transplantation, Higher Creatinine Levels in Hepatitis C Virus Patients, and Donor Age Are Predictors of Mortality in Long-Term Analysis of Late Acute Rejection in Liver Transplantation.

    PubMed

    Nacif, Lucas Souto; Pinheiro, Rafael Soares; de Arruda Pécora, Rafael Antônio; Tanigawa, Ryan Yukimatsu; Rocha-Santos, Vinicius; Andraus, Wellington; Alves, Venancio Avancini Ferreira; D'Albuquerque, Luiz Carneiro

    2017-01-10

    BACKGROUND Late acute rejection (LAR) differs in its clinical and histological presentation and management from early acute rejection. This clinical entity is not completely understood; thus, we aimed to identify significant prognostic factors that can influence post-transplant survival in LAR patients. The purpose of this study was to evaluate the incidence and post-transplant survival of patients from a single center with a focus on late acute rejection. MATERIAL AND METHODS From January 2002 to June 2013, all liver biopsies from patients with rejection were scored using the Banff criteria. The groups were compared, and simple and multiple logistic regression and survival curves were created. RESULTS A total of 779 liver transplants were performed; 585 patients with no rejections and 194 patients with rejections were analyzed. The overall incidence of LAR was 6.7%, and there was a higher prevalence of early acute cellular rejection than LAR. The mean time to LAR was 564 days (median 214 days, range 91-2642). LAR had a more severe grade (35.3%) than early acute rejection (23.5%). The survival rates were similar between both modalities for the long-term period. Worse mortality rates were observed in liver re-transplantation (HR 4.77; p<0.0001); in hepatitis C virus patients with increased creatinine levels (HR 22.48; p=0.016); and in donors >41 years of age (OR 2.1; p=0.047) in a long-term analysis of LAR. CONCLUSIONS Liver re-transplantation, higher creatinine levels in hepatitis C virus patients, and donor age were predictors of mortality in this long-term analysis of late acute rejection in liver transplantation.

  9. Stressful events and coping related to acute and sub-acute whiplash-associated disorders.

    PubMed

    Pettersson, Susanne; Bring, Annika; Åsenlöf, Pernilla

    2017-03-01

    Purpose To describe daily stressors affecting and coping strategies employed by individuals with whiplash-associated disorders (WAD) immediately to one month (acute) and three to four months (sub-acute) after injury events using a daily coping assessment. Levels of pain, anxiety, depressed mood and activity are also compared between phases. Method A descriptive prospective design with a content analysis approach was used. Participants completed daily coping assessments for one week during both acute and sub-acute phases. Main measure was whiplash-associated disorders-daily coping assessment (WAD-DCA). Results Nine participants used words describing recovery in the sub-acute phase; 31 described stressful events during both phases. Most frequently reported stressors were related to "symptoms", "emotions" and "occupations/studies". These were equally reported during both phases. Cognitive coping strategies were employed more often during the sub-acute phase (p = 0.008). The only behavioral strategy that increased in prevalence over time was the "relaxed" strategy (p = 0.001). Anxiety levels declined over time (p = 0.022). Conclusion The reported stressors were largely uniform across both acute and sub-acute phases; however, the use of cognitive coping strategies increased over time. The WAD-DCA captures individual stressors and coping strategies employed during a vulnerable phase of rehabilitation and can thus provide information that is useful to clinical practice. Implications for rehabilitation The WAD-DCA provides valuable information for clinical practice when employed during early phases of whiplash-associated disorder development. Reported stressors during the acute and sub-acute phases are essentially the same, whereas cognitive coping strategies grow in prevalence over time. Tailored treatments in early phases of whip-lash associated disorders may benefit from strategies aimed at matching patient-specific stressors with contextually adapted coping

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

    PubMed

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

    2008-02-01

    To study the value of detection of both preoperative soluble CD30 (sCD30) and hepatocyte growth factor (HGF) level 5 days after transplantation in the diagnosis of acute rejection of renal allograft. Preoperative serum sCD30 levels and HGF level 5 days after transplantation were determined in 65 renal-transplant recipients using enzyme-linked immunosorbent assay. The recipients were divided according to the sCD30 levels positivity. Receiver operating characteristic (ROC) curves were used to assess the value of HGF level on day 5 posttransplantation for diagnosis of acute renal allograft rejection, and the value of combined assay of the sCD30 and HGF levels was also estimated. After transplantation, 26 recipients developed graft rejection and 39 had uneventful recovery without rejection. With the cut-off value of sCD30 of 120 U/ml, the positivity rate of sCD30 was significantly higher in recipients with graft rejection than in those without (61.5% vs 17.9%, P<0.05). Recipients with acute rejection showed also significantly higher HGF levels on day 5 posttransplantation than those without rejection (P<0.05). ROC curve analysis indicated that HGF levels on day 5 posttransplantation was a good marker for diagnosis of acute renal allograft rejection, and at the cut-off value of 90 ug/L, the diagnostic sensitivity was 84.6% and specificity 76.9%. Evaluation of both the sCD30 and HGF levels significantly enhanced the diagnostic accuracy of acute graft rejection. Combined assay of serum sCD30 and HGF levels offers a useful means for diagnosis of acute renal allograft rejection.

  11. Patient-reported non-adherence and immunosuppressant trough levels are associated with rejection after renal transplantation.

    PubMed

    Scheel, Jennifer; Reber, Sandra; Stoessel, Lisa; Waldmann, Elisabeth; Jank, Sabine; Eckardt, Kai-Uwe; Grundmann, Franziska; Vitinius, Frank; de Zwaan, Martina; Bertram, Anna; Erim, Yesim

    2017-03-29

    Different measures of non-adherence to immunosuppressant (IS) medication have been found to be associated with rejection episodes after successful transplantation. The aim of the current study was to investigate whether graft rejection after renal transplantation is associated with patient-reported IS medication non-adherence and IS trough level variables (IS trough level variability and percentage of sub-therapeutic IS trough levels). Patient-reported non-adherence, IS trough level variability, percentage of sub-therapeutic IS trough levels, and acute biopsy-proven late allograft rejections were assessed in 267 adult renal transplant recipients who were ≥12 months post-transplantation. The rate of rejection was 13.5%. IS trough level variability, percentage of sub-therapeutic IS trough levels as well as patient-reported non-adherence were all significantly and positively associated with rejection, but not with each other. Logistic regression analyses revealed that only the percentage of sub-therapeutic IS trough levels and age at transplantation remained significantly associated with rejection. Particularly, the percentage of sub-therapeutic IS trough levels is associated with acute rejections after kidney transplantation whereas IS trough level variability and patient-reported non-adherence seem to be of subordinate importance. Patient-reported non-adherence and IS trough level variables were not correlated; thus, non-adherence should always be measured in a multi-methodological approach. Further research concerning the best combination of non-adherence measures is needed.

  12. CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation.

    PubMed

    Roux, Antoine; Mourin, Gisèle; Fastenackels, Solène; Almeida, Jorge R; Iglesias, Maria Candela; Boyd, Anders; Gostick, Emma; Larsen, Martin; Price, David A; Sacre, Karim; Douek, Daniel C; Autran, Brigitte; Picard, Clément; Miranda, Sandra de; Sauce, Delphine; Stern, Marc; Appay, Victor

    2013-07-01

    Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao

    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, andmore » 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.« less

  14. Histologic damage of lung allografts according to magnitude of acute rejection in the re-isotransplant model.

    PubMed

    Marui, Tsutomu; Iwata, Hisashi; Shirahashi, Koyo; Matsumoto, Shinsuke; Mizuno, Yoshimasa; Matsui, Masafumi; Takemura, Hirofumi

    2008-06-01

    Graft damage due to acute rejection has been reported as one of the risk factors in the chronic stage of cardiac and renal allografts. This study was designed to elucidate the histologic changes of grafts after ongoing acute allograft rejection was discontinued in models of lung re-isotransplantation. WKAH rat lungs were orthotopically transplanted into F344 recipients. Three days (3A group) and 5 days (5A group) after the first allotransplantation, the grafts were re-isotransplanted back into the WKAH rats (3RA and 5RA groups, respectively). Five days (5I group) after the first isotransplantation, the grafts were re-isotransplanted back into the WKAH rats (5RI group). The grafts were removed 30 and 60 days after re-isotransplantation and assessed histologically. Typical acute allograft rejection developed in the 3A and 5A groups, and the changes were reduced after re-isotransplantation, although they remained significantly greater in the 5RA group than in the 3RA and 5RI groups. For intimal hyperplasia, the graft score 60 days after re-isotransplantation in the 5RA group was significantly higher than in the 5RI and 3RA groups. The changes in airway inflammation were significantly greater in the 5RA group than in the 3RA and 5RI groups at 60 days. Peribronchiolar fibrosis was significantly more frequent in the 5RA and 3RA groups than in the 5RI group. Acute rejection and airway inflammation corresponded to the magnitude of rejection before retransplantation. Significant intimal hyperplasia developed in severe acute rejection, and peribronchiolar fibrosis occurred after the first acute rejection.

  15. Proteomic signatures in plasma during early acute renal allograft rejection.

    PubMed

    Freue, Gabriela V Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F; Ng, Raymond T; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H; Wilson-McManus, Janet; McManus, Bruce M; Keown, Paul A; McMaster, W Robert

    2010-09-01

    Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change >or=1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and beta(2)-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and

  16. Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection*

    PubMed Central

    Freue, Gabriela V. Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P.; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F.; Ng, Raymond T.; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H.; Wilson-McManus, Janet; McManus, Bruce M.; Keown, Paul A.; McMaster, W. Robert

    2010-01-01

    Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change ≥1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and β2-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and

  17. Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection.

    PubMed

    Gregson, Aric L; Hoji, Aki; Injean, Patil; Poynter, Steven T; Briones, Claudia; Palchevskiy, Vyacheslav; Weigt, S Sam; Shino, Michael Y; Derhovanessian, Ariss; Sayah, David; Saggar, Rajan; Ross, David; Ardehali, Abbas; Lynch, Joseph P; Belperio, John A

    2015-12-15

    The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes. To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence. Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed. AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets. Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation.

  18. Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection

    PubMed Central

    Hoji, Aki; Injean, Patil; Poynter, Steven T.; Briones, Claudia; Palchevskiy, Vyacheslav; Sam Weigt, S.; Shino, Michael Y.; Derhovanessian, Ariss; Saggar, Rajan; Ross, David; Ardehali, Abbas; Lynch, Joseph P.; Belperio, John A.

    2015-01-01

    Rationale: The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes. Objectives: To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence. Methods: Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed. Measurements and Main Results: AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets. Conclusions: Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation. PMID:26308930

  19. Eotaxin/CCL11 expression by infiltrating macrophages in rat heart transplants during ongoing acute rejection.

    PubMed

    Zweifel, Martin; Mueller, Christoph; Schaffner, Thomas; Dahinden, Clemens; Matozan, Katja; Driscoll, Robert; Mohacsi, Paul

    2009-10-01

    Eotaxin/CCL11 chemokine is expressed in different organs, including the heart, but its precise cellular origin in the heart is unknown. Eotaxin is associated with Th2-like responses and exerts its chemotactic effect through the chemokine receptor-3 (CCR3), which is also expressed on mast cells (MC). The aim of our study was to find the cellular origin of eotaxin in the heart, and to assess whether expression is changing during ongoing acute heart transplant rejection, indicating a correlation with mast cell infiltration which we observed in a previous study. In a model of ongoing acute heart transplant rejection in the rat, we found eotaxin mRNA expression within infiltrating macrophages, but not in mast cells, by in situ-hybridization. A five-fold increase in eotaxin protein in rat heart transplants during ongoing acute rejection was measured on day 28 after transplantation, compared to native and isogeneic control hearts. Eotaxin concentrations in donor hearts on day 28 after transplantation were significantly higher compared to recipient hearts, corroborating an origin of eotaxin from cells within the heart, and not from the blood. The quantitative comparison of eotaxin mRNA expression between native hearts, isografts, and allografts, respectively, revealed no statistically significant difference after transplantation, probably due to an overall increase in the housekeeping gene's 18S rRNA during rejection. Quantitative RT-PCR showed an increase in mRNA expression of CCR3, the receptor for eotaxin, during ongoing acute rejection of rat heart allografts. Although a correlation between increasing eotaxin expression by macrophages and mast cell infiltration is suggestive, functional studies will elucidate the role of eotaxin in the process of ongoing acute heart transplant rejection.

  20. [Sub-acute thyroiditis in a patient on immunosuppressive treatment].

    PubMed

    D'Amico, Giovanna; Di Crescenzo, Vincenzo; Caleo, Alessia; Garzi, Alfredo; Vitale, Mario

    2013-01-01

    Sub-acute thyroiditis or De Quervain's thyroiditis is a viral, inflammatory disease which causes the serum release of thyroidal hormones and hyperthyroidism. The pathogenesis of thyroid follicle damage is unclear because the exclusive viral action or a concomitant autoimmune component, determined by the lymphoid infiltrate remain to be assessed. We describe the case of a patient under immunosuppressive treatment, who developed sub-acute thyroiditis with hormone release and hyperthyroidism. The patient, while was under immunosuppressive treatment for kidney transplant, exhibited a clinical picture and hormonal profile of hyperthyroidism. Thyroid scintiscan exhibited an extremely low uptake. Fine-needle cytologic diagnosis was granulomatous sub-acute thyroiditis (De Quervain's thyroiditis). This case suggests the primary or even exclusive role of the viral infection in hormone release and hyperthyroidism in sub-acute thyroiditis, excluding an autoimmune component.

  1. Rituximab-Related Late-Onset Neutropenia in Kidney Transplant Recipients Treated for Antibody-Mediated Acute Rejection.

    PubMed

    Ahmadi, Fatemeh; Dashti-Khavidaki, Simin; Khatami, Mohammad-Reza; Lessan-Pezeshki, Mahboob; Khalili, Hossein; Khosravi, Malihe

    2017-08-01

    Kidney transplant is a new area for use of rituximab, which is being used to treat acute antibody-mediated rejection or as an induction agent in ABO- or HLA-incompatible grafts. We report on late-onset neutropenia in rituximab-treated kidney transplant recipients with antibody-mediated rejection. This observational prospective study was performed on kidney transplant recipients with clinically suspicious or biopsy-proven antibody-mediated rejection treated with plasmapheresis plus intravenous immunoglobulin with (cases) or without (controls) rituximab. Compared with none of the controls, 4 of 6 patients (66.7%) in the rituximab-treated group experienced late-onset neutropenia 35 to 93 days after the last dose of rituximab. The course of neutropenia was complicated by endocarditis in 1 patient, resulting in his death just because of a lack of valvular surgery. Increased use of rituximab to treat antibody-mediated rejection among kidney transplant recipients requires attention to its late-onset adverse event, neutropenia. Although asymptomatic in some patients, kidney transplant recipients treated concomitantly with plasmapheresis and mycophenolate mofetil are predisposed to hypogammaglobulinemia, and monitoring of patients for infections is required.

  2. 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

  3. High serum soluble CD30 does not predict acute rejection in liver transplant patients.

    PubMed

    Matinlauri, I; Höckerstedt, K; Isoniemi, H

    2006-12-01

    Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.

  4. Relation between pretransplant serum levels of soluble CD30 and acute rejection during the first 6 months after a kidney transplant.

    PubMed

    Shooshtarizadeh, Tina; Mohammadali, Ali; Ossareh, Shahrzad; Ataipour, Yousef

    2013-06-01

    The immunologic status of kidney allograft recipients affects transplant outcome. High levels of pretransplant serum soluble CD30 correlate with an increased risk of acute rejection. Studies show conflicting results. We evaluated the relation between pretransplant serum sCD30 levels with the risk of posttransplant acute kidney rejection in renal transplant recipients. This prospective cohort study was performed between March 2010 and March 2011 on 77 kidney transplant recipients (53 men [68.8%], 24 women [31.2%]; mean age, 41 ± 14 y). Serum samples were collected 24 hours before transplant and analyzed for soluble CD30 levels by enzyme-linked immunosorbent assay. Patients were followed for 6 months after transplant. Acute biopsy-proven rejection episodes were recorded, serum creatinine levels were measured, and glomerular filtration rates were calculated at the first and sixth months after transplant. Preoperative serum soluble CD30 levels were compared in patients with and without rejection. The mean pretransplant serum soluble CD30 level was 92.1 ± 47.3 ng/mL. At 6 months' follow-up, 10 patients experienced acute rejection. Mean pretransplant soluble CD30 levels were 128.5 ± 84 ng/mL versus 86.7 ± 37 ng/mL in patients with and without acute rejection episodes (P = .008). At 100 ng/mL, the sensitivity, specificity, and positive and negative predictive values of pretransplant serum soluble CD30 level to predict acute rejection were 70%, 73.6%, 29.1%, and 94.3%. We showed a significant relation between pretransplant serum soluble CD30 levels and acute allograft rejection. High pretransplant levels of serum soluble CD30 can be a risk factor for kidney transplant rejection, and its high negative predictive value at various cutoffs make it useful to find candidates with a low risk of acute rejection after transplant.

  5. Spleen tyrosine kinase contributes to acute renal allograft rejection in the rat

    PubMed Central

    Ramessur Chandran, Sharmila; Tesch, Greg H; Han, Yingjie; Woodman, Naomi; Mulley, William R; Kanellis, John; Blease, Kate; Ma, Frank Y; Nikolic-Paterson, David J

    2015-01-01

    Kidney allografts induce strong T-cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (Syk) is expressed by most leucocytes, except mature T cells, and is involved in intracellular signalling following activation of the Fcγ-receptor, B-cell receptor and some integrins. A role for Syk signalling has been established in antibody-dependent native kidney disease, but little is known of Syk in acute renal allograft rejection. Sprague–Dawley rats underwent bilateral nephrectomy and received an orthotopic Wistar renal allograft. Recipient rats were treated with a Syk inhibitor (CC0482417, 30 mg/kg/bid), or vehicle, from 1 h before surgery until being killed 5 days later. Vehicle-treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (T cells, macrophages, neutrophils and NK cells) and deposition of IgM, IgG and C3. Immunostaining identified Syk expression by many infiltrating leucocytes. CC0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. CC0482417 failed to prevent T-cell infiltration and activation within the allograft. However, CC0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for Syk in acute renal allograft rejection. Syk inhibition may be a useful addition to T-cell-based immunotherapy in renal transplantation. PMID:25529862

  6. Scabies in a bilateral hand allograft recipient: An additional mimicker of acute skin rejection in vascularized composite allotransplantation.

    PubMed

    Kanitakis, Jean; Morelon, Emmanuel

    2017-06-01

    Vascularized composite tissue allografts include skin, which frequently undergoes, in the early post-graft period, acute rejections. The diagnosis of acute rejection may be difficult as it can be mimicked by several dermatoses. We present a bilateral hand allograft recipient who developed, 16.5 years post-graft, cutaneous lesions raising suspicion about rejection. Physical examination and skin biopsy were diagnostic of scabies. This ectoparasitosis should be added in the list of dermatoses that can mimic allograft rejection in vascular composite allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The role of FDG-PET in detecting rejection after liver transplantation.

    PubMed

    Watson, Ashley M; Bhutiani, Neal; Philips, Prejesh; Davis, Eric G; Eng, Mary; Cannon, Robert M; Jones, Christopher M

    2018-05-15

    The activation and increased metabolic activity of T cells in acute cellular rejection could allow fluoro-2-deoxyglucose positron emission tomography to be utilized for detection of acute cellular rejection. The objective of this study was to evaluate the effectiveness of fluoro-2-deoxyglucose positron emission tomography in detecting acute cellular rejection in the clinical setting. Fluoro-2-deoxyglucose positron emission tomography studies were performed on 88 orthotopic liver transplant patients at 7 and 17 days postoperatively (first positron emission tomography and second positron emission tomography, respectively). Additional studies were performed if patients had suspicion of rejection and at resolution of rejection (third positron emission tomography and fourth positron emission tomography, respectively). A circular region of interest was placed over the liver for semiquantitative evaluation of fluoro-2-deoxyglucose positron emission tomography images by means of standard uptake values. Eighteen of 88 patients in our study (20.5%) had histologically proven acute cellular rejection during a 16 ± 11 day follow-up. There was no significant difference between the standard uptake values of first positron emission tomography among non-rejecters versus rejecters (2.05 ±0.46 non-rejecters versus 1.82 ± 0.40 rejecters, P = .127). Within the rejection cohort, the standard uptake values from the third positron emission tomography (rejection) were higher compared to the first positron emission tomography (baseline) (2.41 ± 0.48 third positron emission tomography versus 1.82 ± 0.41 first positron emission tomography, P < .001). Increased signal on fluoro-2-deoxyglucose positron emission tomography over baseline is associated with acute cellular rejection in liver transplant recipients. Additional prospective validation studies are essential to define the role of fluoro-2-deoxyglucose positron emission tomography scan as an early marker for acute cellular

  8. Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers.

    PubMed

    Zambernardi, Agustina; Chiodetti, Ana; Meier, Dominik; Cabanne, Ana; Nachman, Fabio; Solar, Héctor; Rumbo, Carolina; Gondolesi, Gabriel E; Rumbo, Martin

    2014-12-01

    Acute cellular rejection (ACR) and infections are leading causes of graft loss and death in intestinal transplant patients. Our aim was to evaluate the impact of maintenance immunosuppressive therapies on the expression of pro-inflammatory mediators in small bowel at ACR diagnosis. We analyzed expression levels of Th1-associated genes, IFNG, CXCL10, and CXCL11 by qPCR in 46 selected graft biopsies unequivocally assigned to mild ACR (n = 14) or normal histopathology and clinical condition (n = 32) from 15 patients receiving two different immunosuppressive (IS) schemes. Double treatment: corticosteroids and tacrolimus (n = 17) and triple treatment: sirolimus or mycophenolate mofetil in addition to the basal therapy (n = 29). IFNG, CXCL10, and CXCL11 were induced during rejection (p < 0.05; p < 0.005, and p < 0.05, respectively). However, when rejection and control groups were classified according to immunosuppressive treatment, in the rejection group, significant differences of IFNG, CXCL10, and CXCL11 expression (p < 0.001; p < 0.005, and 0.01, respectively) were detected, whereas no differences were observed in the control group. Gene expression of Th1 response mediators is higher during ACR. Triple IS group showed significantly lower expression of pro-inflammatory Th1 mediators during mild ACR indicating that use of these markers to monitor rejection can be affected by the IS treatment used. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Reduction of Acute Rejection by Bone Marrow Mesenchymal Stem Cells during Rat Small Bowel Transplantation

    PubMed Central

    Zhang, Wen; Wu, Ben-Juan; Fu, Nan-Nan; Zheng, Wei-Ping; Don, Chong; Shen, Zhong-Yang

    2014-01-01

    Background Bone marrow mesenchymal stem cells (BMMSCs) have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats. Methods Heterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control), isogeneically transplanted rats (BN-BN) and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg) cells were assessed at each time point. Results Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th)1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL)-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ while upregulating IL-10 and transforming growth factor (TGF)-β expression and increasing Treg levels. Conclusion BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation. PMID:25500836

  10. Treating reading comprehension deficits in sub-acute brain injury rehabilitation: Identifying clinical practice and management.

    PubMed

    Watter, Kerrin; Copley, Anna; Finch, Emma

    There is limited evidence for cognitive-communication reading comprehension (CCRC) interventions for adults following acquired brain injury (ABI), particularly during sub-acute rehabilitation. The purpose of this study was to investigate the clinical practice of speech-language pathologists (SLPs) with CCRC deficits during sub-acute ABI rehabilitation and compare it to the best available evidence. An electronic survey was used to gather information from clinicians across Australia regarding clinical practice in the areas of assessment, intervention, treatment hierarchies and service delivery; survey questions were developed from an extensive review of the literature and expert clinician opinion. Survey findings were then compared with the literature in the form of a systematic review. Surveyed clinicians provided multiple interventions for CCRC rehabilitation, including impairment based (94.7%), activity based (94.7%) and reading strategy interventions (100.0%). Five strategies were used by >94% of SLPs (highlighting, identifying main points/wh- questioning, re-reading, summarising, reducing visual load). When compared with the literature, strong similarities were found for strategy-based interventions and individual service delivery, with broad similarities for functional and impairment-based interventions, and impairment based treatment hierarchies. Strong differences in assessment were identified. Strategy use reported in clinical practice (100.0% SLPs) was higher than in the literature. Further investigation into the effectiveness of specific reading strategies for people with ABI is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2006-09-01

    In renal transplant recipients elevated soluble serum CD30 levels are associated with increased rejection and graft loss. We sought to determine the sCD30 plasma levels before and after kidney transplantation and to assess whether sCD30 was a predictive factor of immunological risk. sCD30 plasma levels were determined by an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before as well as 7, 15, and 21 days after transplantation. Eighteen patients developed acute allograft rejection (group I) and 34 patients showed uneventful courses (group II). Before transplantation sCD30 plasma levels were elevated in both groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients with acute rejection showed higher relative levels of plasma sCD30 on days 7 and 15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a difference that was significant for group I (P = .0003) and not significant for group II (P = .09). On day 21, sCD30 decreased in the two groups but remained higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed acute rejection only (26.4%), a difference that was not significant (P > .05). If we consider 100 U/mL as the minimum predictive level for allograft rejection, our results suggested that levels of sCD30 should be taken into consideration with the presence of HLA-antibodies detectable before and after transplantation, especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 < RR < 10.91)]. These data suggested that measurement of plasma sCD30 is a useful procedure for the recognition of rejection in its earliest stages.

  12. Lipoxygenase products in the urine correlate with renal function and body temperature but not with acute transplant rejection.

    PubMed

    Reinhold, Stephan W; Scherl, Thomas; Stölcker, Benjamin; Bergler, Tobias; Hoffmann, Ute; Weingart, Christian; Banas, Miriam C; Kollins, Dmitrij; Kammerl, Martin C; Krüger, Bernd; Kaess, Bernhard; Krämer, Bernhard K; Banas, Bernhard

    2013-02-01

    Acute transplant rejection is the leading cause of graft loss in the first months after kidney transplantation. Lipoxygenase products mediate pro- and anti-inflammatory actions and thus we aimed to correlate the histological reports of renal transplant biopsies with urinary lipoxygenase products concentrations to evaluate their role as a diagnostic marker. This study included a total of 34 kidney transplant recipients: 17 with an acute transplant rejection and 17 controls. LTE4, LTB4, 12-HETE and 15-HETE concentrations were measured by enzyme immunoassay. Urinary lipoxygenase product concentrations were not significantly changed during an acute allograft rejection. Nevertheless, LTB4 concentrations correlated significantly with the body temperature (P ≤ 0.05) 3 months after transplantation, and 12- and 15-HETE concentrations correlated significantly with renal function (P ≤ 0.05) 2 weeks after transplantation. In conclusion, our data show a correlation for LTB4 with the body temperature 3 months after transplantation and urinary 12- and 15-HETE concentrations correlate positively with elevated serum creatinine concentrations but do not predict acute allograft rejection.

  13. Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles.

    PubMed

    Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

    2014-01-01

    Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may be related to acute renal allograft

  14. Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles

    PubMed Central

    Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

    2014-01-01

    Objectives: Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. Methods: MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. Results: A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. Conclusions: We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may

  15. Pretransplant soluble CD30 level has limited effect on acute rejection, but affects graft function in living donor kidney transplantation.

    PubMed

    Kim, Myoung Soo; Kim, Hae Jin; Kim, Soon Il; Ahn, Hyung Joon; Ju, Man Ki; Kim, Hyun Jung; Jeon, Kyung Ock; Kim, Yu Seun

    2006-12-27

    Serum soluble CD30 (sCD30) levels might be a useful marker of immunologic status in pre transplant (Tx) recipients. We retrospectively correlated preTx sCD30 levels (high versus low) on postTx graft survival, incidence of acute rejection, and graft function using stored preTx serum. Of 254 recipients who underwent kidney Tx, 120 recipients were enrolled under the uniform criteria (living donor, age >25 years, viral hepatitis free, diabetes free). The preTx sCD30 was not significantly associated with differences in graft survival rate during 47.5+/-11.4 months of follow-up (P = 0.5901). High sCD30 (> or =115 U/ml) was associated with a higher incidence of clinically or pathologically defined acute rejection than low sCD30, but the difference was not statistically significant (33.9% vs. 22.4%, P = 0.164). The response rate to antirejection therapy in patients with high sCD30 was inferior to those with low sCD30, but also was not statistically significant (33.3% vs. 7.7%, P = 0.087). However, mean serum creatinine levels in high sCD30 patients at one month, one year, and three years postTx were significantly different from those with low sCD30 (P < 0.05). In multiple regression analysis, acute rejection episodes, donor age, kidney weight/recipient body weight ratio, and preTx sCD30 levels were independent variables affecting the serum creatinine level three years postTx. PreTx sCD30 level has a limited effect on the incidence of acute rejection and response to antirejection treatment, but inversely and independently affects serum creatinine level after living donor kidney transplantation.

  16. The Relationship of the Severity and Category of Acute Rejection With Intimal Arteritis Defined in Banff Classification to Clinical Outcomes.

    PubMed

    Wu, Kaiyin; Budde, Klemens; Schmidt, Danilo; Neumayer, Hans-Helmut; Rudolph, Birgit

    2015-08-01

    It is unclear if the category of acute rejection with intimal arteritis (ARV) is relevant to short- and long-term clinical outcomes and if the graft outcomes are affected by the severity of intimal arteritis. One hundred forty-eight ARV episodes were reviewed and categorized according to the 2013 Banff criteria of AMR: T cell-mediated rejection with intimal arteritis (v) lesion (TCMRV; n = 78), total antibody-mediated rejection with v lesion (AMRV), which were further divided into suspicious AMRV (n = 37) and AMRV (n = 33). The Banff scores of intimal arteritis (v1, v2 and v3) represented low, moderate, and high ARV severity. The grafts with TCMRV, suspicious AMRV (sAMRV), and AMRV showed similar responses to antirejection therapy, whereas the grafts with v2- or v3-ARV responded significantly poorer compared to those with v1-ARV. The 8-year death-censored graft survival (DCGS) rate was 56.8% of TCMRV versus 34.1% of total AMRV (Log rank, P = 0.03), but the 1- and 5-year DCGS rates were comparable between the 2 groups; moreover, the 1-, 5-, and 8-year DCGS rates of v1-ARV were evidently higher than v2- and v3-ARV (each pairwise comparison to v1-AVR yields P < 0.01); in contrast, the DCGS rates were similar between sAMRV and AMRV. The existing donor-specific antibodies or moderate microvascular inflammation or C4d-positive staining or intensive tubulointerstitial inflammation played a less significant role on the long-term graft survival. Compared to the category, the ARV severity is more closely associated with the initial response to antirejection therapy and long-term graft failure. The sAMRV and AMRV might represent a spectrum of the same disorder.

  17. Correlations between A/H1N1 influenza and acute cellular rejection in liver transplantation patients.

    PubMed

    Stucchi, R S B; Boin, I F S F; Angerami, R Nogueira; Sinckoc, V; Sa, F Cesar; Seva-Pereira, T; Escanhoela, C A Fazzio

    2010-12-01

    Influenza is a common cause of respiratory infection in transplant recipients. It is expected that A/H1N1 influenza virus causes more severe disease in solid-organ recipients. Our goal was to describe two A/H1N1 infections that occurred after Orthotopic liver transplantation followed by acute allograft rejection episodes. From March 2009 to March 2010 we observe two liver transplant patients with symptoms suggestive of A/H1N1 infection. The diagnosis was out based on a temperature of 37.8°C (100°F) or higher and the presence of a cough or using materials from anasopharyngeal and oropharyngeal swabs a sore throat. The diagnosis was confirmed by viral RNA detection by real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR) using materials from nasopharyngeal and oropharyngeal swabs. We performed the RT-PCR assay for A/H1N1 detection in a liver biopsy from one patient. Both patients were treated with usual doses of oseltamivir (75 mg twice daily for 5 days). One patient developed acute bacterial sinusitis requiring antibiotic therapy. Thereafter the liver enzymes increased and transplant biopsies showed moderate-to-severe acute cellular rejection. They were treated with corticosteroids. The liver enzymes normalized after 3 months. A/H1N1 influenza can lead to a severe acute cellular rejection episode with corticosteroid resistant treatment in liver transplant patients. Transplant centers should be aware of a possible relationship between A/H1N1 infections and acute allograft rejection episodes. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Casemix classification payment for sub-acute and non-acute inpatient care, Thailand.

    PubMed

    Khiaocharoen, Orathai; Pannarunothai, Supasit; Zungsontiporn, Chairoj; Riewpaiboon, Wachara

    2010-07-01

    There is a need to develop other casemix classifications, apart from DRG for sub-acute and non-acute inpatient care payment mechanism in Thailand. To develop a casemix classification for sub-acute and non-acute inpatient service. The study began with developing a classification system, analyzing cost, assigning payment weights, and ended with testing the validity of this new casemix system. Coefficient of variation, reduction in variance, linear regression, and split-half cross-validation were employed. The casemix for sub-acute and non-acute inpatient services contained 98 groups. Two percent of them had a coefficient of variation of the cost of higher than 1.5. The reduction in variance of cost after the classification was 32%. Two classification variables (physical function and the rehabilitation impairment categories) were key determinants of the cost (adjusted R2 = 0.749, p = .001). Validity results of split-half cross-validation of sub-acute and non-acute inpatient service were high. The present study indicated that the casemix for sub-acute and non-acute inpatient services closely predicted the hospital resource use and should be further developed for payment of the inpatients sub-acute and non-acute phase.

  19. Correlation of IMPDH1 gene polymorphisms with subclinical acute rejection and mycophenolic acid exposure parameters on day 28 after renal transplantation.

    PubMed

    Kagaya, Hideaki; Miura, Masatomo; Saito, Mitsuru; Habuchi, Tomonori; Satoh, Shigeru

    2010-08-01

    The risk of acute rejection in patients with higher exposure to mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), might be due to inosine 5'-monophosphate dehydrogenase (IMPDH) polymorphisms. The correlations with subclinical acute rejection, IMPDH1 polymorphisms and MPA exposure on day 28 post-transplantation were investigated in 82 Japanese recipients. Renal transplant recipients were given combination immunosuppressive therapy consisting of tacrolimus and 1.0, 1.5 or 2.0 g/day of MMF in equally divided doses every 12 hr at designated times. There were no significant differences in the incidence of subclinical acute rejection between IMPDH1 rs2278293 or rs2278294 polymorphisms (p = 0.243 and 0.735, respectively). However, in the high MPA night-time exposure range (AUC > 60 microg x h/ml and C(0 )> or = 1.9 microg/ml), there was a significant difference in the incidence of subclinical acute rejection between IMPDH1 rs2278293 A/A, A/G and G/G genotypes (each p = 0.019), but not the IMPDH1 rs2278294 genotype. In the higher daytime MPA exposure range, patients with the IMPDH1 rs2278293 G/G genotype also tended to develop subclinical acute rejection. In patients with the IMPDH rs2278293 A/A genotype, the risk of subclinical acute rejection episode tends to be low and the administration of MMF was effective. The risk of subclinical acute rejection for recipients who cannot adapt in therapeutic drug monitoring (TDM) of MPA seems to be influenced by IMPDH1 rs2278293 polymorphism. The prospective analysis of IMPDH1 rs2278293 polymorphism as well as monitoring of MPA plasma concentration after transplantation might help to improve MMF therapy.

  20. Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs.

    PubMed

    Milovancev, Milan; Schmiedt, Chad W; Bentley, Ellison; Schwab, Michelle; Dubielzig, Richard R; Gendron-Fitzpatrick, Annette P; McAnulty, Jonathan F

    2007-01-01

    To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs. Prospective, pilot study. Eight healthy, unrelated, DEA mismatched, adult mongrel dogs. All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed. Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis. In this experimental model, a CAP-CsA-prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time. A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.

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

    PubMed

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

    2017-01-01

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

  2. Late acute humoral rejection in low-risk renal transplant recipients induced with an interleukin-2 receptor antagonist and maintained with standard therapy: preliminary communication.

    PubMed

    Morales, J; Contreras, L; Zehnder, C; Pinto, V; Elberg, M; Araneda, S; Herzog, C; Calabran, L; Aguiló, J; Ferrario, M; Buckel, E; Fierro, J A

    2011-01-01

    Low-risk renal transplant recipients treated with standard immunosuppressive therapy including interleukin-2 receptor (IL-2R) antagonist show a low incidence of early rejection episodes but few reports have examined the incidence and severity of late rejection processes. This study evaluated retrospectively cellular and antibody-mediated rejection (AMR) among 42 recipients selected because they showed low panel-reactive-antibodies, short cold ischemia time, no delayed graft function, and therapy including basiliximab (Simulect) induction. The mean observation time was 6.6 years. Sixty-seven percent of donors were deceased. Ten-year patient and death-censored graft survivals were 81% and 78%, respectively. Seven patients lost their kidneys due to nonimmunologic events. The seven recipients who experienced cellular rejection episodes during the first posttransplant year had them reversed with steroids. Five patients displayed late acute AMR causing functional deterioration in four cases including 1 graft loss. De novo sensitization occurred in 48% of recipients including patients without clinical rejection. In conclusion, long-term follow-up of kidney transplant recipients selected by a low immunologic risk showed a persistent risk of de novo sensitization evolving to acute AMR in 11% of cases. Although immunologic events were related to late immunosuppressive reduction, most graft losses were due to nonimmunologic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis.

    PubMed

    Ishibashi, Naoya; Watanabe, Tatsuaki; Kanehira, Masahiko; Watanabe, Yui; Hoshikawa, Yasushi; Notsuda, Hirotsugu; Noda, Masafumi; Sakurada, Akira; Ohkouchi, Shinya; Kondo, Takashi; Okada, Yoshinori

    2018-03-15

    Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

  4. Incidence and Severity of Acute Cellular Rejection in Recipients Undergoing Adult Living Donor or Deceased Donor Liver Transplantation123

    PubMed Central

    Shaked, Abraham; Ghobrial, R. Mark; Merion, Robert M.; Shearon, Tempie H.; Emond, Jean C.; Fair, Jeffrey H.; Fisher, Robert A.; Kulik, Laura M.; Pruett, Timothy L.; Terrault, Norah A.

    2013-01-01

    Living donor liver transplantation (LDLT) may have better immunological outcomes compared to deceased donor liver transplantation (DDLT). The aim of this study was to analyze the incidence of acute cellular rejection (ACR) after LDLT and DDLT. Data from the Adult-to-Adult Living Donor Liver Transplantation (A2ALL) Retrospective Cohort Study on 593 liver transplants done between May 1998 and March 2004 were studied (380 LDLT; 213 DDLT). Median LDLT and DDLT follow-up was 778 and 713 days, respectively. Rates of clinically treated and biopsy-proven ACR were compared. There were 174 (46%) LDLT and 80 (38%) DDLT recipients with ≥1 clinically treated episodes of ACR, whereas 103 (27%) LDLT and 58 (27%) DDLT recipients had ≥1 biopsy-proven ACR episode. A higher proportion of LDLT recipients had clinically treated ACR (P=0.052), but this difference was largely attributable to one center. There were similar proportions of biopsy-proven rejection (P=0.97) and graft loss due to rejection (P=0.16). Longer cold ischemia time was associated with a higher rate of ACR in both groups despite much shorter median cold ischemia time in LDLT. These data do not show an immunological advantage for LDLT, and therefore do not support the application of unique post-transplant immunosuppression protocols for LDLT recipients. PMID:19120082

  5. Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study.

    PubMed

    Zapf, Antonia; Gwinner, Wilfried; Karch, Annika; Metzger, Jochen; Haller, Hermann; Koch, Armin

    2015-09-15

    Reliable and timely detection of acute rejection in renal transplant patients is important to preserve the allograft function and to prevent premature allograft failure. The current gold standard for the rejection diagnosis is an allograft biopsy which is usually performed upon an unexplained decline in allograft function. Because of the invasiveness of the biopsy, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry analysis of urine samples. The aim of this study is to examine the diagnostic accuracy of mass spectrometry analysis in urine for the diagnosis of acute rejections using the biopsy as gold-standard. The study is an ongoing prospective, single-arm, multicentre, phase 3 diagnostic accuracy study. It started in October 2011 and will be concluded in December 2015. Patient within the first year after transplantation who are scheduled for a biopsy to clarify unexplained impairment of the allograft are consecutively recruited into the study. The overall sample size (n = 600) was calculated to demonstrate a sensitivity of 83 % and a specificity of 70 % for a one-sided type one error of 2.5 % and a power of 80 % per hypothesis. Biopsy evaluation and mass spectrometry analysis of urine samples (obtained immediately before biopsy) are performed independently by different readers without knowledge from the respective other assessment. The follow-up observation period is 6 months. For the primary analysis, the lower limits of the two-sided 95 % Wald confidence intervals for sensitivity and specificity will be compared with the pre-specified thresholds (83 % for sensitivity and 70 % for specificity). In secondary analyses the predictive values, the diagnostic measures in subgroups, and the clinical course will be assessed. Previous phase 2 diagnostic accuracy studies (in small selected study populations) provided sufficient evidence to suggest mass spectrometry on urine samples as a promising approach to detect

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

    PubMed

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

    2012-09-01

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

  7. Structural shifts of fecal microbial communities in rats with acute rejection after liver transplantation.

    PubMed

    Xie, Yirui; Luo, Zhuanbo; Li, Zhengfeng; Deng, Min; Liu, Hao; Zhu, Biao; Ruan, Bing; Li, Lanjuan

    2012-08-01

    Bacterial translocation and the development of sepsis after orthotopic liver transplantation (OLT) may be promoted by immunological damage to the intestinal mucosa or by quantitative and qualitative changes in intestinal microbiota. This study monitored structural shifts of gut microbiota in rats with OLT using PCR-denaturing gradient gel electrophoresis (DGGE) and real-time quantitative PCR (RT-qPCR). RT-qPCR targets six major microorganisms (Domain Bacteria, Bacteroides, Bifidobacteria, Enterobacteriaceae, Lactobacillus and Clostridium leptum subgroup). Isograft, Allograft and Sham model were studied. Bacterial translocation to host organs and plasma endotoxin were determined. Alteration in gut microbiota was associated with the elevation of plasma endotoxin and a higher rate of bacterial translocation (BT) to liver in rats with acute rejection. Dynamic analysis of DGGE fingerprints showed that the gut microbiota structure of animals in the three groups was similar before the operation. But significant alterations in the composition of fecal microbiota in Allograft group were observed at 1 and 2 weeks after the OLT. The acute rejection was accompanied by the shifts of gut microbiota towards members of Bacteroides and Ruminococcus. Results from RT-qPCR indicated that Bacteroides significantly increased at 2 weeks after the OLT, whereas numbers of Bifidobacterium spp. decreased at 1 week and recovered at 2 weeks after the OLT. In summary, our data showed that rats with acute rejection after OLT exhibited significant structure shifts in the gut microbiota which dominant by overgrowth of Bacteroides and Ruminococcus, and these were associated with elevation of plasma endotoxin and higher rate of BT.

  8. C4d-the witness of humoral rejection.

    PubMed

    de Gouveia, R H; Vitorino, E; Ramos, S; Rebocho, M J; Queirós E Melo, J; Martins, A P; Moura, M L C

    2009-04-01

    Acute antibody-mediated (humoral) rejection is a major cause of morbidity, graft loss, and mortality among heart transplant patients. Herein we have presented our experience using C4d to characterize humoral rejection. All nonformalin-fixed cardiac graft biopsies (protocol or emergency) received between May 2007 and May 2008 were examined by immunofluorescence for C4d. One hundred twelve endomyocardial biopsies from 25 transplanted patients included 20 males and 5 females of ages ranging from 3 to 71 years. The number of biopsies per subject varied from 1 to 11; the timespan between transplantation and the diagnostic biopsies ranged from days to 8 years. Thirteen biopsies showed acute humoral rejection (intramyocardial capillaries positive for C4d); 31, acute cellular rejection (grades 1R, 2R); 7, both humoral and cellular rejection; and 1, acute humoral rejection and allograft vasculopathy. Some of the positive biopsies belonged to the same person, and some to transplanted individuals with signs and symptoms suggestive of rejection, while others did not. The persistence of humoral rejection, despite the disappearance of a cellular component, correlated with slower clinicoechocardiographic improvement. C4d positivity is a morphologic sign of humoral rejection. It may hasten the appearance and/or worsening of allograft vasculopathy independent of patient age or posttransplantation time.

  9. The prognostic value of sleep patterns in disorders of consciousness in the sub-acute phase.

    PubMed

    Arnaldi, Dario; Terzaghi, Michele; Cremascoli, Riccardo; De Carli, Fabrizio; Maggioni, Giorgio; Pistarini, Caterina; Nobili, Flavio; Moglia, Arrigo; Manni, Raffaele

    2016-02-01

    This study aimed to evaluate, through polysomnographic analysis, the prognostic value of sleep patterns, compared to other prognostic factors, in patients with disorders of consciousness (DOCs) in the sub-acute phase. Twenty-seven patients underwent 24-h polysomnography and clinical evaluation 3.5 ± 2 months after brain injury. Their clinical outcome was assessed 18.5 ± 9.9 months later. Polysomnographic recordings were evaluated using visual and quantitative indexes. A general linear model was applied to identify features able to predict clinical outcome. Clinical status at follow-up was analysed as a function of the baseline clinical status, the interval between brain injury and follow-up evaluation, patient age and gender, the aetiology of the injury, the lesion site, and visual and quantitative sleep indexes. A better clinical outcome was predicted by a visual index indicating the presence of sleep integrity (p=0.0006), a better baseline clinical status (p=0.014), and younger age (p=0.031). Addition of the quantitative sleep index strengthened the prediction. More structured sleep emerged as a valuable predictor of a positive clinical outcome in sub-acute DOC patients, even stronger than established predictors (e.g. age and baseline clinical condition). Both visual and quantitative sleep evaluation could be helpful in predicting clinical outcome in sub-acute DOCs. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Sub-acute neuropathy in patients with African tick bite fever.

    PubMed

    Jensenius, Mogens; Fournier, Pierre-Edouard; Fladby, Tormod; Hellum, Kjell Block; Hagen, Tormod; Priø, Tine; Christiansen, Merete Skovdal; Vene, Sirkka; Raoult, Didier; Myrvang, Bjørn

    2006-01-01

    African tick bite fever (ATBF) caused by Rickettsia africae is an emerging health problem in travellers to sub-Saharan Africa. We here present 6 patients with evidence of long-lasting sub-acute neuropathy following ATBF contracted during safari trips to southern Africa. Three patients developed radiating pain, paresthaesia and/or motor weakness of extremities, 2 had hemi-facial pain and paresthaesia, and 1 developed unilateral sensorineural hearing loss. When evaluated 3-26 months after symptom onset, cerebrospinal fluid samples from 5 patients were negative for R. africae PCR and serology, but revealed elevated protein content in 3 and mild pleocytosis in 1 case. Despite extensive investigations, no plausible alternative causes of neuropathy could be identified. Treatment with doxycycline in 2 patients had no clinical effect. Given the current increase of international safari tourism to sub-Saharan Africa, more cases of sub-acute neuropathy following ATBF may well be encountered in Europe and elsewhere in the y to come.

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

    PubMed

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

    2009-01-01

    Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

  12. Acute rejection characteristics from a prospective, randomized, double-blind, placebo-controlled multicenter trial of early corticosteroid withdrawal.

    PubMed

    Gaber, A Osama; Moore, Linda W; Alloway, Rita R; Woodle, E Steve; Pirsch, John; Shihab, Fuad; Henning, Alice; Fitzsimmons, William; Holman, John; Reisfield, Robin; First, M Roy

    2013-02-27

    This report characterizes acute rejection and rejection outcomes in subjects randomized to continuous corticosteroid therapy (CCS) or early corticosteroid withdrawal (CSWD; 7 days after transplantation) in the Astellas Blinded CSWD Trial. The Astellas Blinded CSWD Trial was a 5-year, prospective, multicenter, randomized, double-blind trial of early CCS withdrawal in 386 kidney transplant recipients (195 CCS and 191 CSWD). Tacrolimus and mycophenolate mofetil were required as well as either rabbit antithymocyte globulin or interleukin-2 receptor antibody induction. Biopsy-confirmed acute rejection (BCAR) was grade 1A or higher by Banff criteria. This report also provides borderline changes (BL) that did not meet Banff grade 1A included with BCAR (BCAR+BL). BCAR+BL was 25 (12.8%) in CCS group and 42 (22.0%) in CSWD group (P=0.022). Early BCAR+BL (first 90 days after transplantation) was less frequent in CCS (n=5 [2.6%]) than in CSWD (n=22 [11.5%]; P<0.001). Among non-African-American subjects, early BCAR+BL occurred more often in CSWD (n=20 [12.7%]) versus CCS (n=2 [1.3%]; P<0.001). Late acute rejection (>2 years) occurred more often in African-American subjects in CCS (n=5 [13.9%]) than in CSWD (n=0; P=0.056). Risk factors were CSWD (hazard ratio [HR], 4.72; P<0.002) and human leukocyte antigen mismatch (HR, 1.48; P<0.005) for early BCAR+BL and CSWD (HR, 1.9; P<0.02), human leukocyte antigen mismatch (HR, 1.2; P<0.01), and age (HR, 0.97; P<0.002) for 5-year rejection. The HR for graft loss associated with BCAR+BL was 8.8. BCAR+BL may occur more frequently during the early period after transplantation under an early CSWD regimen with tacrolimus plus induction compared with CCS, particularly among non-African-Americans.

  13. Pre-transplant immune state defined by serum markers and alloreactivity predicts acute rejection after living donor kidney transplantation.

    PubMed

    Vondran, Florian W R; Timrott, Kai; Kollrich, Sonja; Steinhoff, Ann-Kristin; Kaltenborn, Alexander; Schrem, Harald; Klempnauer, Juergen; Lehner, Frank; Schwinzer, Reinhard

    2014-09-01

    Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF < BL < AR. Relying on serum analysis only, multivariate logistic regression (logit link function) yielded a prognostic score for prediction of rejection with 75.0% sensitivity and 69.2% specificity. Patients with rejection showed markedly higher pre-transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Obesity in pediatric kidney transplant recipients and the risks of acute rejection, graft loss and death.

    PubMed

    Ladhani, Maleeka; Lade, Samantha; Alexander, Stephen I; Baur, Louise A; Clayton, Philip A; McDonald, Stephen; Craig, Jonathan C; Wong, Germaine

    2017-08-01

    Obesity is prevalent in children with chronic kidney disease (CKD), but the health consequences of this combination of comorbidities are uncertain. The aim of this study was to evaluate the impact of obesity on the outcomes of children following kidney transplantation. Using data from the ANZDATA Registry (1994-2013), we assessed the association between age-appropriate body mass index (BMI) at the time of transplantation and the subsequent development of acute rejection (within the first 6 months), graft loss and death using adjusted Cox proportional hazards models. Included in our analysis were 750 children ranging in age from 2 to 18 (median age 12) years with a total of 6597 person-years of follow-up (median follow-up 8.4 years). Overall, at transplantation 129 (17.2%) children were classified as being overweight and 61 (8.1%) as being obese. Of the 750 children, 102 (16.2%) experienced acute rejection within the first 6 months of transplantation, 235 (31.3%) lost their allograft and 53 (7.1%) died. Compared to children with normal BMI, the adjusted hazard ratios (HR) for graft loss in children who were underweight, overweight or diagnosed as obese were 1.05 [95% confidence interval (CI) 0.70-1.60], 1.03 (95% CI 0.71-1.49) and 1.61 (95% CI 1.05-2.47), respectively. There was no statistically significant association between BMI and acute rejection [underweight: HR 1.07, 95% CI 0.54-2.09; overweight: HR 1.42, 95% CI 0.86-2.34; obese: HR 1.83, 95% CI 0.95-3.51) or patient survival (underweight: HR 1.18, 95% CI 0.54-2.58, overweight: HR 0.85, 95% CI 0.38-1.92; obese: HR 0.80, 95% CI 0.25-2.61). Over 10 years of follow-up, pediatric transplant recipients diagnosed with obesity have a substantially increased risk of allograft failure but not acute rejection of the graft or death.

  15. Alteration of Cardiac Deformation in Acute Rejection in Pediatric Heart Transplant Recipients.

    PubMed

    Chanana, Nitin; Van Dorn, Charlotte S; Everitt, Melanie D; Weng, Hsin Yi; Miller, Dylan V; Menon, Shaji C

    2017-04-01

    The objective of this study is to assess changes in cardiac deformation during acute cellular- and antibody-mediated rejection in pediatric HT recipients. Pediatric HT recipients aged ≤18 years with at least one episode of biopsy-diagnosed rejection from 2006 to 2013 were included. Left ventricular systolic S (SS) and SR (SSr) data were acquired using 2D speckle tracking on echocardiograms obtained within 12 h of right ventricular endomyocardial biopsy. A mixed effect model was used to compare cardiac deformation during CR (Grade ≥ 1R), AMR (pAMR ≥ 2), and mixed rejection (CR and AMR positive) versus no rejection (Grade 0R and pAMR 0 or 1). A total of 20 subjects (10 males, 50%) with 71 rejection events (CR 35, 49%; AMR 21, 30% and mixed 15, 21%) met inclusion criteria. The median time from HT to first biopsy used for analysis was 5 months (IQR 0.25-192 months). Average LV longitudinal SS and SSr were reduced significantly during rejection (SS: -17.2 ± 3.4% vs. -10.7 ± 4.5%, p < 0.001 and SSr: -1.2 ± 0.2 s - 1 vs. -0.9 ± 0.3 s - 1 ; p < 0.001) and in all rejection types. Average LV short-axis radial SS was reduced only in CR compared to no rejection (p = 0.04), while average LV circumferential SS and SSr were reduced significantly in AMR compared to CR (SS: 18.9 ± 4.2% vs. 20.8 ± 8.8%, p = 0.03 and SSr: 1.35 ± 0.8 s - 1 vs. 1.54 ± 0.9 s - 1 ; p = 0.03). In pediatric HT recipients, LV longitudinal SS and SSr were reduced in all rejection types, while LV radial SS was reduced only in CR. LV circumferential SS and SSr further differentiated between CR and AMR with a significant reduction seen in AMR as compared to CR. This novel finding suggests mechanistic differences between AMR- and CR-induced myocardial injury which may be useful in non-invasively predicting the type of rejection in pediatric HT recipients.

  16. Acute Rejection in Renal Transplant Patients of a Hospital in Bogota, Colombia

    PubMed Central

    García, P.; Huerfano, M; Rodríguez, M; Caicedo, A; Berrío, F; Gonzalez, C

    2016-01-01

    Background: Renal transplantation is the best treatment for end stage renal disease. Acute graft rejection is one of the main complications and may influence graft survival. Objective: To determine the incidence and features of acute cellular rejection (ACR) episodes confirmed by biopsy. Methods: We studied a cohort of 175 patients who underwent renal transplantation between 2004 and 2012 to determine the cumulative incidence of ACR confirmed by biopsy and to identify the associated risk factors using multivariate analysis. Results: The one-year patient survival was 96.6%; the graft survival was 93.7%. The incidence of ACR within one year was 14.3%, of which 46% were observed within 6 months following transplantation. The most frequently observed ACR type was 1B according to the Banff classification system (42%). A relationship between ACR and receipt of a kidney from expanded criteria donors was observed, both in univariate and adjusted multiple log-binomial regression analyses, but only 6.3% of patients received extended criteria donor kidneys. No other relationships between variables were found. Conclusion: ACR frequency in this study was similar to that of other cohorts reported previously. We need a bigger sample of renal transplants from expanded criteria donors, PRA and DSA test to support the results. PMID:27721962

  17. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence.

    PubMed

    Sellarés, J; de Freitas, D G; Mengel, M; Reeve, J; Einecke, G; Sis, B; Hidalgo, L G; Famulski, K; Matas, A; Halloran, P F

    2012-02-01

    We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming to assign a cause to every failure. We followed 315 allograft recipients who underwent indication biopsies at 6 days to 32 years posttransplant. Sixty kidneys progressed to failure in the follow-up period (median 31.4 months). Failure was rare after T-cell-mediated rejection and acute kidney injury and common after antibody-mediated rejection or glomerulonephritis. We developed rules for using biopsy diagnoses, HLA antibody and clinical data to explain each failure. Excluding four with missing information, 56 failures were attributed to four causes: rejection 36 (64%), glomerulonephritis 10 (18%), polyoma virus nephropathy 4 (7%) and intercurrent events 6 (11%). Every rejection loss had evidence of antibody-mediated rejection by the time of failure. Among rejection losses, 17 of 36 (47%) had been independently identified as nonadherent by attending clinicians. Nonadherence was more frequent in patients who progressed to failure (32%) versus those who survived (3%). Pure T-cell-mediated rejection, acute kidney injury, drug toxicity and unexplained progressive fibrosis were not causes of loss. This prospective cohort indicates that many actual failures after indication biopsies manifest phenotypic features of antibody-mediated or mixed rejection and also underscores the major role of nonadherence. © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  18. Acute liver allograft antibody-mediated rejection: an inter-institutional study of significant histopathological features.

    PubMed

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

    2014-10-01

    Acute antibody-mediated rejection (AMR) occurs in a small minority of sensitized liver transplant recipients. Although histopathological characteristics have been described, specific features that could be used (1) to make a generalizable scoring system and (2) to trigger a more in-depth analysis are needed to screen for this rare but important finding. Toward this goal, we created training and validation cohorts of putative acute AMR and control cases from 3 high-volume liver transplant programs; these cases were evaluated blindly by 4 independent transplant pathologists. Evaluations of hematoxylin and eosin (H&E) sections were performed alone without knowledge of either serum donor-specific human leukocyte antigen alloantibody (DSA) results or complement component 4d (C4d) stains. Routine histopathological features that strongly correlated with severe acute AMR included portal eosinophilia, portal vein endothelial cell hypertrophy, eosinophilic central venulitis, central venulitis severity, and cholestasis. Acute AMR inversely correlated with lymphocytic venulitis and lymphocytic portal inflammation. These and other characteristics were incorporated into models created from the training cohort alone. The final acute antibody-mediated rejection score (aAMR score)--the sum of portal vein endothelial cell hypertrophy, portal eosinophilia, and eosinophilic venulitis divided by the sum of lymphocytic portal inflammation and lymphocytic venulitis--exhibited a strong correlation with severe acute AMR in the training cohort [odds ratio (OR) = 2.86, P < 0.001] and the 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 = 86%) and another that optimized sensitivity at a score > 1.0 (sensitivity = 81%, specificity = 71%). In conclusion, the routine histopathological features of the aAMR score can be used to

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Forbes, R.D.; Lowry, R.P.; Gomersall, M.

    1985-07-01

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

  20. Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients.

    PubMed

    Levitsky, Josh; Goldberg, David; Smith, Abigail R; Mansfield, Sarah A; Gillespie, Brenda W; Merion, Robert M; Lok, Anna S F; Levy, Gary; Kulik, Laura; Abecassis, Michael; Shaked, Abraham

    2017-04-01

    Acute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors. We analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors. At least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes. Contrary to previous data, acute rejection after liver transplant is associated with significantly increased

  1. Increased levels of circulating nitrates and impaired endothelium-mediated vasodilation suggest multiple roles of nitric oxide during acute rejection of pulmonary allografts.

    PubMed

    Wiklund, L; Lewis, D H; Sjöquist, P O; Nilsson, F; Tazelaar, H; Miller, V M; McGregor, C G

    1997-05-01

    Experiments were designed to determine whether changes in pulmonary artery function could be reduced by treatment with a lipid peroxidation inhibitor (H 290/51) during acute rejection of pulmonary allografts. Single lung transplantation was performed in three groups of dogs: group 1 was maintained on immunosuppression for 8 days after operation (immunosuppressed, n = 5); in group 2, immunosuppression was discontinued on postoperative day 5, so that rejection occurred on postoperative day 8 (rejecting, n = 6); in group 3, immunosuppression was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 (25 mg/kg) was given perorally for 3 days (rejecting + H 290/51, n = 6). Plasma nitric oxide (NO(x)) was measured by use of chemoluminescence. On postoperative day 8 rejection was observed in groups 2 and 3. Contractions to angiotensin I and endothelium-dependent relaxations to adenosine diphosphate were reduced in pulmonary arteries from rejecting lungs. Responses of rings from dogs treated with H 290/51 were similar to those from rejecting lungs. Rejection did not alter relaxations to exogenous nitric oxide. However, plasma levels of NO(x) increased significantly during rejection independently of treatment with H 290/51. Results of this study confirm that endothelium-dependent relaxation of pulmonary arteries is reduced during acute rejection of lung allografts. The result extends these observations to suggest that treatment with a lipid peroxidation inhibitor neither protects the pulmonary artery function nor affects levels of circulating NO(x). Therefore mechanisms other than lipid peroxidation participate in vascular changes associated with allograft rejection.

  2. Increased intracellular adenosine triphosphate level as an index to predict acute rejection in kidney transplant recipients.

    PubMed

    Wang, Xu-Zhen; Jin, Zhan-Kui; Tian, Xiao-Hui; Xue, Wu-Jun; Tian, Pu-Xun; Ding, Xiao-Ming; Zheng, Jin; Li, Yang; Jing, Xin; Luo, Zi-Zhen

    2014-01-01

    Peripheral blood CD4+ T cell adenosine triphosphate (ATP) release has been reported to be an adjunct tool to evaluate global cellular immune response in solid-organ transplant recipients. However, the correlation between the ATP level and rejection was controversial. The aim of this prospective clinical study was to explore the association between the intracellular ATP level and the occurrence, progression, and treatment of acute rejection (AR) episodes, determine the predicting value of intracellular ATP level for AR in kidney transplant (KT) recipients. In the period of October 2011 to October 2012, 140 KT recipients were recruited and followed for six months after transplantation. Patients were categorized into stable group and AR group according to their clinical course. Whole blood samples were collected pretransplantation, and at 7, 14, 21, and 28days, and at 2, 3, 4, 5 and 6months post-transplantation. Additional blood samples were obtained from AR patients on the day AR occurred, on the day before and 3 and 7days after intravenous anti-rejection therapy started, and on the day when AR reversed. The intracellular ATP in CD4+ T cells was detected by ImmuKnow Immune Cell Function Assay according to the manufacturer's instruction. The absolute number of CD4+ T cells and the trough levels of tacrolimus and cyclosporine were also measured. The ATP level detected on the day AR occurred (627.07±149.85ng/ml) was obviously higher than that of the stable group (320.48±149.11ng/ml, P<0.05). ATP value decreased to 265.35±84.33ng/m at the end of anti-rejection therapy, which was obviously lower than that measured on the day before the anti-rejection therapy started (665.87±162.85ng/ml, P<0.05). ROC analysis revealed that increased intracellular adenosine triphosphate level showed better sensitivity and specificity than those obtained using single time point detection (89.5% vs 85.0%;95.0% vs 88.9%). The best cutoff value was 172.55ng/ml. A positive correlation

  3. Acute and sub-chronic toxicity studies of honokiol microemulsion.

    PubMed

    Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2015-04-01

    The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

  4. 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.

  5. Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection.

    PubMed

    Slavcev, Antonij; Lácha, Jiri; Honsová, Eva; Sajdlová, Helena; Lodererová, Alena; Vitko, Stefan; Skibová, Jelena; Striz, Ilja

    2005-06-01

    Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P < 0.001). However, there was a substantial difference in the level of decrease of sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P < 0.04. Multifactorial analysis showed that antibodies to HLA class II antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.

  6. Clinical and pathological features of kidney transplant patients with concurrent polyomavirus nephropathy and rejection-associated endarteritis

    PubMed Central

    McGregor, Stephanie M; Chon, W James; Kim, Lisa; Chang, Anthony; Meehan, Shane M

    2015-01-01

    AIM: To describe the clinicopathologic features of concurrent polyomavirus nephropathy (PVN) and endarteritis due to rejection in renal allografts. METHODS: We searched our electronic records database for cases with transplant kidney biopsies demonstrating features of both PVN and acute rejection (AR). PVN was defined by the presence of typical viral cytopathic effect on routine sections and positive polyomavirus SV40 large-T antigen immunohistochemistry. AR was identified by endarteritis (v1 by Banff criteria). All cases were subjected to chart review in order to determine clinical presentation, treatment course and outcomes. Outcomes were recorded with a length of follow-up of at least one year or time to nephrectomy. RESULTS: Of 94 renal allograft recipients who developed PVN over an 11-year period at our institution, we identified 7 (7.4%) with viral cytopathic changes, SV40 large T antigen staining, and endarteritis in the same biopsy specimen, indicative of concurrent PVN and AR. Four arose after reduction of immunosuppression (IS) (for treatment of PVN in 3 and tuberculosis in 1), and 3 patients had no decrease of IS before developing simultaneous concurrent disease. Treatment consisted of reduced oral IS and leflunomide for PVN, and anti-rejection therapy. Three of 4 patients who developed endarteritis in the setting of reduced IS lost their grafts to rejection. All 3 patients with simultaneous PVN and endarteritis cleared viremia and were stable at 1 year of follow up. Patients with endarteritis and PVN arising in a background of reduced IS had more severe rejection and poorer outcome. CONCLUSION: Concurrent PVN and endarteritis may be more frequent than is currently appreciated and may occur with or without prior reduction of IS. PMID:26722657

  7. 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

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

    PubMed

    Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

    2013-10-21

    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.

  9. Reliability and validity of the de Morton Mobility Index in individuals with sub-acute stroke.

    PubMed

    Braun, Tobias; Marks, Detlef; Thiel, Christian; Grüneberg, Christian

    2018-02-04

    To establish the validity and reliability of the de Morton Mobility Index (DEMMI) in patients with sub-acute stroke. This cross-sectional study was performed in a neurological rehabilitation hospital. We assessed unidimensionality, construct validity, internal consistency reliability, inter-rater reliability, minimal detectable change and possible floor and ceiling effects of the DEMMI in adult patients with sub-acute stroke. The study included a total sample of 121 patients with sub-acute stroke. We analysed validity (n = 109) and reliability (n = 51) in two sub-samples. Rasch analysis indicated unidimensionality with an overall fit to the model (chi-square = 12.37, p = 0.577). All hypotheses on construct validity were confirmed. Internal consistency reliability (Cronbach's alpha = 0.94) and inter-rater reliability (intraclass correlation coefficient = 0.95; 95% confidence interval: 0.92-0.97) were excellent. The minimal detectable change with 90% confidence was 13 points. No floor or ceiling effects were evident. These results indicate unidimensionality, sufficient internal consistency reliability, inter-rater reliability, and construct validity of the DEMMI in patients with a sub-acute stroke. Advantages of the DEMMI in clinical application are the short administration time, no need for special equipment and interval level data. The de Morton Mobility Index, therefore, may be a useful performance-based bedside test to measure mobility in individuals with a sub-acute stroke across the whole mobility spectrum. Implications for Rehabilitation The de Morton Mobility Index (DEMMI) is an unidimensional measurement instrument of mobility in individuals with sub-acute stroke. The DEMMI has excellent internal consistency and inter-rater reliability, and sufficient construct validity. The minimal detectable change of the DEMMI with 90% confidence in stroke rehabilitation is 13 points. The lack of any floor or ceiling effects on hospital admission indicates

  10. "Snowmelt Sign" and "Corkscrew Microvessels" Predicting Epithelium Regeneration After Acute Rejection of Small-Bowel Transplantation: A Case Report.

    PubMed

    Chung, C-S; Lee, T-H; Chiu, C-T; Chen, Y

    2017-12-01

    Intestinal failure characterized by inadequate maintenance of nutrition via normal intestinal function comprises a group of disorders with many different causes. If parenteral nutrition dependency develops, which is associated with higher mortality and complications, it is considered for intestine transplantation. However, the graft failure rate is not low, and acute cellular rejection is one of the most important reasons for graft failure. As a result, early identification of rejection and timely modification of anti-rejection medications have been considered to be associated with better graft and patient survival rates. The diagnostic gold standard for rejection is mainly based on histology, but hours of delay by pathology may occur. Some researchers investigated the association of endoscopic images with graft rejection to provide timely diagnosis. In this study, we present the first case report with characteristic features under magnifying endoscopy with a narrow-band imaging system to predict epithelial regeneration and improvement of graft rejection in a patient with small-bowel transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. T1 Mapping by Cardiac Magnetic Resonance and Multidimensional Speckle-Tracking Strain by Echocardiography for the Detection of Acute Cellular Rejection in Cardiac Allograft Recipients.

    PubMed

    Sade, Leyla Elif; Hazirolan, Tuncay; Kozan, Hatice; Ozdemir, Handan; Hayran, Mutlu; Eroglu, Serpil; Pirat, Bahar; Sezgin, Atilla; Muderrisoglu, Haldun

    2018-04-14

    The aim of this study was to test the hypothesis that echocardiographic strain imaging, by tracking subtle alterations in myocardial function, and cardiac magnetic resonance T1 mapping, by quantifying tissue properties, are useful and complement each other to detect acute cellular rejection in heart transplant recipients. Noninvasive alternatives to endomyocardial biopsy are highly desirable to monitor acute cellular rejection. Surveillance endomyocardial biopsies, catheterizations, and echocardiograms performed serially according to institutional protocol since transplantation were retrospectively reviewed. Sixteen-segment global longitudinal strain (GLS) and circumferential strain were measured before, during, and after the first rejection and at 2 time points for patients without rejection using Velocity Vector Imaging for the first part of the study. The second part, with cardiac magnetic resonance added to the protocol, served to validate previously derived strain cutoffs, examine the progression of strain over time, and to determine the accuracy of strain and T1 measurements to define acute cellular rejection. All tests were performed within 48 h. Median time to first rejection (16 grade 1 rejection, 15 grade ≥2 rejection) was 3 months (interquartile range: 3 to 36 months) in 49 patients. GLS and global circumferential strain worsened significantly during grade 1 rejection and ≥2 rejection and were independent predictors of any rejection. In the second part of the study, T1 time ≥1,090 ms, extracellular volume ≥32%, GLS >-14%, and global circumferential strain ≥-24% had 100% sensitivity and 100% negative predictive value to define grade ≥2 rejection with 70%, 63%, 55%, and 35% positive predictive values, respectively. The combination of GLS >-16% and T1 time ≥1,060 ms defined grade 1 rejection with 91% sensitivity and 92% negative predictive value. After successful treatment, T1 times decreased significantly. T1 mapping and

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

    PubMed

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

    2016-04-01

    There are conflicting data on the role of the lectin pathway of complement activation and its recognition molecules in acute rejection and outcome after transplantation. To help resolve this we analyzed polymorphisms and serum levels of lectin pathway components in 710 consecutive kidney transplant recipients enrolled in the nationwide Swiss Transplant Cohort Study, together with all biopsy-proven rejection episodes and 1-year graft and patient survival. Functional mannose-binding lectin (MBL) levels were determined in serum samples, and previously described MBL2, ficolin 2, and MBL-associated serine protease 2 polymorphisms were genotyped. Low MBL serum levels and deficient MBL2 diplotypes were associated with a higher incidence of acute cellular rejection during the first year, in particular in recipients of deceased-donor kidneys. This association remained significant (hazard ratio 1.75, 95% confidence interval 1.18-2.60) in a Cox regression model after adjustment for relevant covariates. In contrast, there was no significant association with rates of antibody-mediated rejection, patient death, early graft dysfunction or loss. Thus, results in a prospective multicenter contemporary cohort suggest that MBL2 polymorphisms result in low MBL serum levels and are associated with acute cellular rejection after kidney transplantation. Since MBL deficiency is a relatively frequent trait in the normal population, our findings may lead to individual risk stratification and customized immunosuppression. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  13. Clinically significant changes in the emotional condition of relatives of patients with severe traumatic brain injury during sub-acute rehabilitation.

    PubMed

    Norup, Anne; Kristensen, Karin Spangsberg; Poulsen, Ingrid; Nielsen, Christina Löfvquist; Mortensen, Erik Lykke

    2013-09-01

    To investigate clinically significant change in the emotional condition of relatives of patients with severe traumatic brain injury during sub-acute rehabilitation. Participants were 62 pairs of relatives and patients. Relatives completed the anxiety and depression scales from the Symptom Checklist-90-R (SCL-90-R) when the patients were admitted to sub-acute rehabilitation and at discharge. Improvement in emotional condition was investigated using the following criteria: (i) statistically reliable improvement; and (ii) clinically significant change (CSC). At admission, 53.2% and 58.1% of relatives had scores above cut-off values on the anxiety and depression scales, respectively. On the anxiety scale 69.7% of these experienced a reliable improvement according to the Reliable Change Index (RCI) and 45.5% also obtained CSC, as their end-point was below the cut-off value. On the depression scale the corresponding figures were 44.4% and 41.7%, respectively. When comparing relatives with and without CSC, we found that CSC in symptoms of anxiety was associated with significantly better functional improvement during rehabilitation and a shorter period of post-traumatic amnesia in the patients. Of the relatives who reported scores above cut-off values on the anxiety and depression scales at patient's admission, approximately 40% experienced CSC in anxiety and depression during the patient's rehabilitation. Relatives of patients experiencing improvement during inpatient rehabilitation are more likely to experience CSC in anxiety.

  14. Effects of Hypercapnia on Acute Cellular Rejection after Lung Transplantation in Rats.

    PubMed

    Tan, Jing; Liu, Yanhong; Jiang, Tao; Wang, Ling; Zhao, Can; Shen, Dongfang; Cui, Xiaoguang

    2018-01-01

    Hypercapnia alleviates pulmonary ischemia-reperfusion injury, regulates T lymphocytes, and inhibits immune reaction. This study aimed to evaluate the effect of hypercapnia on acute cellular rejection in a rat lung transplantation model. Recipient rats in sham-operated (Wistar), isograft (Wistar to Wistar), and allograft (Sprague-Dawley to Wistar) groups were ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague-Dawley to Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min during reperfusion (n = 8). Recipients were euthanized 7 days after transplantation. The hypercapnia group showed a higher oxygenation index (413 ± 78 vs. 223 ± 24), lower wet weight-to-dry weight ratio (4.23 ± 0.54 vs. 7.04 ± 0.80), lower rejection scores (2 ± 1 vs. 4 ± 1), and lower apoptosis index (31 ± 6 vs. 57 ± 4) as compared with the allograft group. The hypercapnia group showed lower CD8 (17 ± 4 vs. 31 ± 3) and CD68 (24 ± 3 vs. 43 ± 2), lower CD8 T cells (12 ± 2 vs. 35 ± 6), and higher CD4/CD8 ratio (2.2 ± 0.6 vs. 1.1 ± 0.4) compared to the allograft group. Tumor necrosis factor-α (208 ± 40 vs. 292 ± 49), interleukin-2 (30.6 ± 6.7 vs. 52.7 ± 8.3), and interferon-γ (28.1 ± 4.9 vs. 62.7 ± 10.1) levels in the hypercapnia group were lower than those in allograft group. CD4, CD4 T cells, and interleukin-10 levels were similar between groups. Hypercapnia ameliorated acute cellular rejection in a rat lung transplantation model.

  15. Explaining the paradoxical rejection-aggression link: the mediating effects of hostile intent attributions, anger, and decreases in state self-esteem on peer rejection-induced aggression in youth.

    PubMed

    Reijntjes, Albert; Thomaes, Sander; Kamphuis, Jan H; Bushman, Brad J; de Castro, Bram Orobio; Telch, Michael J

    2011-07-01

    People are strongly motivated to feel accepted by others. Yet when faced with acute peer rejection they often aggress against the very peers they desire acceptance from, which may lead to further rejection. The present experiment tests three potential mediators of aggressive responses to acute peer rejection in the critical developmental stage of early adolescence. Participants (N=185, M(age)=11.5 years) completed personal profiles that were allegedly evaluated online by peers. After receiving negative or neutral peer feedback, participants could aggress against the same peers who had evaluated them. Rejected participants attributed more hostile intent to the peers, were angrier, showed a greater reduction in state self-esteem, and were more aggressive. Mediational analyses showed that hostile intent attributions mediated the acute peer rejection-aggression relationship, whereas increases in anger and decreases in state self-esteem did not. Thus, acute peer rejection evokes hostile intent attributions that, in turn, lead to aggressive reactions. © 2011 by the Society for Personality and Social Psychology, Inc

  16. Causes and impact of specimen rejection in a clinical chemistry laboratory.

    PubMed

    Cao, Liyun; Chen, Meng; Phipps, Ron A; Del Guidice, Robert E; Handy, Beverly C; Wagar, Elizabeth A; Meng, Qing H

    2016-07-01

    Pre-analytical errors necessitate specimen rejection and negatively affect patient safety. Our purpose was to investigate the factors leading to specimen rejection and its impact. Specimen rejections in a clinical chemistry laboratory during a 1-year period were reviewed retrospectively and analyzed for frequency, cause, circumstances, and impact. Of the 837,862 specimens received, 2178 (0.26%) were rejected. The most common reasons for specimen rejection were contamination (n=764, 35.1%), inappropriate collection container/tube (n=330, 15.2%), quantity not sufficient (QNS) (n=329, 15.1%), labeling errors (n=321, 14.7%), hemolyzed specimen (n=205, 9.4%), and clotted specimen (n=203, 9.3%). The analytes most often affected were glucose (n=192, 8.8%); calcium (n=152, 7.0%), magnesium (n=148, 6.8%), potassium (n=137, 6.3%), creatinine (n=100, 4.6%), and blood urea nitrogen (n=97, 4.4%). Outpatient service and blood draw by phlebotomists were associated with low rejection rates (536/493,501 or 0.11% and 368/586,503 or 0.06%, respectively). Recollection due to specimen rejection increased the turnaround time by an average of 108min. The total cost for the recollection was around $43,210 USD with an average cost around $21.9 USD. The factors associated with rejection are remediable by improved training and quality assurance measures. Policies and procedures specific to specimen collection, transportation, and preparation should be strictly followed. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Preventing Rejection

    MedlinePlus

    ... living donor Being a living donor Liver Heart Lung Pancreas Intestine VCA Common diseases Living with devices Before Before the transplant How ... At least one episode of acute rejection is common within the first year ... after transplantation. Therefore, organ recipients should be aware of the ...

  18. Chemistry and haematology sample rejection and clinical impact in a tertiary laboratory in Cape Town.

    PubMed

    Jacobsz, Lourens A; Zemlin, Annalise E; Roos, Mark J; Erasmus, Rajiv T

    2011-10-14

    Recent publications report that up to 70% of total laboratory errors occur in the pre-analytical phase. Identification of specific problems highlights pre-analytic processes susceptible to errors. The rejection of unsuitable samples can lead to delayed turnaround time and affect patient care. A retrospective audit was conducted investigating the rejection rate of routine blood specimens received at chemistry and haematology laboratories over a 2-week period. The reasons for rejection and potential clinical impact of these rejections were investigated. Thirty patient files were randomly selected and examined to assess the impact of these rejections on clinical care. A total of 32,910 specimens were received during the study period, of which 481 were rejected, giving a rejection rate of 1.46%. The main reasons for rejection were inappropriate clotting (30%) and inadequate sample volume (22%). Only 51.7% of rejected samples were repeated and the average time for a repeat sample to reach the laboratory was about 5 days (121 h). Of the repeated samples, 5.1% had results within critical values. Examination of patient folders showed that in 40% of cases the rejection of samples had an impact on patient care. The evaluation of pre-analytical processes in the laboratory, with regard to sample rejection, allowed one to identify problem areas where improvement is necessary. Rejected samples due to factors out of the laboratory's control had a definite impact on patient care and can thus affect customer satisfaction. Clinicians should be aware of these factors to prevent such rejections.

  19. Panel reactive HLA antibodies, soluble CD30 levels, and acute rejection six months following renal transplant.

    PubMed

    Domingues, Elizabeth M F L; Matuck, Teresa; Graciano, Miguel L; Souza, Edison; Rioja, Suzimar; Falci, Mônica C; Monteiro de Carvalho, Deise B; Porto, Luís Cristóvão

    2010-01-01

    Specific anti-human leukocyte antigen antibodies (HLA) in the post-transplant period may be present with acute rejection episodes (ARE), and high soluble CD30 (sCD30) serum levels may be a risk factor for ARE and graft loss. HLA cross-matching, panel reactive antibodies (PRA), and sCD30 levels were determined prior to transplantation in 72 patients. Soluble CD30 levels and PRA were re-assessed at day 7, 14, 21, and 28, and monthly up to the sixth.   Twenty-four subjects had a positive PRA and 17 experienced ARE. Nine of 17 ARE subjects demonstrated positive PRA and 16 had HLA mismatches. Positive PRA was more frequent in ARE subjects (p = 0.03). Eight subjects with ARE had donor-specific antibodies (DSA) in serum samples pre-transplantation, two subjects developed DSA. Three subjects without ARE had positive PRA only in post-transplantation samples. Soluble CD30 levels were higher in pre-transplant samples and ARE subjects than non-ARE subjects (p = 0.03). Post-transplant sCD30 levels were elevated in subjects who experienced rejection and were significantly higher at seven d (p = 0.0004) and six months (p = 0.03). Higher sCD30 levels following transplant were associated with ARE. Elevated sCD30 levels may represent a risk factor for acute rejection. © 2009 John Wiley & Sons A/S.

  20. Recurrent AA Amyloidosis Combined With Chronic Active Antibody-mediated Rejection After Kidney Transplantation.

    PubMed

    Yeo, Min-Kyung; Ham, Young Rok; Choi, Song-Yi; Lee, Yong-Moon; Park, Moon Hyang; Suh, Kwang-Sun

    2017-07-01

    Kidney transplantation for amyloidosis remains a contentious issue. Recurrence of amyloidosis is one of the risks of transplantation. Chronic active antibody-mediated rejection is an important cause of chronic allograft dysfunction. A 47-year-old woman underwent kidney transplantation due to renal AA amyloidosis with unknown etiology. Six years posttransplantation, a kidney biopsy showed AA amyloidosis with chronic active antibody-mediated rejection. Donor-specific antibody class II was positive. The patient underwent intravenous plasmapheresis and treatment with rituximab and colchicine. The relationship between recurrence of amyloidosis and rejection was not obvious. Clinical characteristics of kidney transplantation for AA amyloidosis were subjected to literature review and 315 cases were identified. The incidence of amyloidosis recurrence and acute and chronic rejection rates were 15%, 15%, and 8%, respectively. Five-year patient and graft survival rates were 77% and 82%, respectively. Clinical courses of kidney transplantation in AA amyloidosis were, thus, identified.

  1. [Comparison of clinical and histological diagnosis in kidney post-transplantation period].

    PubMed

    de Castro, M C; Chocair, P R; Saldanha, L B; Nahas, W; Arap, S; Sabbaga, E; Ianhez, L E

    1998-01-01

    To assess the agreement between clinical and histopathological diagnosis in a renal transplantation center, 40 episodes of acute renal failure were studied. Kidney biopsies were performed at the moment that a clinical diagnosis was made by the staff. Nineteen episodes of acute tubular necrosis (ATN), eighteen episodes of acute cellular rejection (ACR), 2 humoral rejections and 1 acute cyclosporin nephrotoxicity episodes were diagnosed. ATN episodes were confirmed by renal biopsy in 84.21%, ACR episodes in 83.33%, humoral rejections in 100%. Renal biopsy showed ATN in the occurrence of clinical cyclosporin nephrotoxicity. Total agreement was 82.5%. There is a good relationship between clinical and histopathological diagnosis in the post-transplantation period. Diagnostic mistakes occurred mainly when oliguria was present.

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

    PubMed

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

    2014-05-01

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

  3. Intestinal microbial variation may predict early acute rejection after liver transplantation in rats.

    PubMed

    Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

    2014-10-27

    Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT.

  4. Intestinal Microbial Variation May Predict Early Acute Rejection after Liver Transplantation in Rats

    PubMed Central

    Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

    2014-01-01

    Background Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. Methods The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Results Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. Conclusion We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT. PMID:25321166

  5. Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants.

    PubMed

    Okazaki, Mikio; Gelman, Andrew E; Tietjens, Jeremy R; Ibricevic, Aida; Kornfeld, Christopher G; Huang, Howard J; Richardson, Steven B; Lai, Jiaming; Garbow, Joel R; Patterson, G Alexander; Krupnick, Alexander S; Brody, Steven L; Kreisel, Daniel

    2007-12-01

    Lung transplantation remains the only therapeutic option for many patients suffering from end-stage pulmonary disease. Long-term success after lung transplantation is severely limited by the development of bronchiolitis obliterans. The murine heterotopic tracheal transplantation model has been widely used for studies investigating pathogenesis of obliterative airway disease and immunosuppressive strategies to prevent its development. Despite its utility, this model employs proximal airway that lacks airflow and is not vascularized. We have developed a novel model of orthotopic vascularized lung transplantation in the mouse, which leads to severe vascular rejection in allogeneic strain combinations. Here we characterize differences in the fate of airway epithelial cells in nonimmunosuppressed heterotopic tracheal and vascularized lung allograft models over 28 days. Up-regulation of growth factors that are thought to be critical for the development of airway fibrosis and interstitial collagen deposition were similar in both models. However, while loss of airway epithelial cells occurred in the tracheal model, airway epithelium remained intact and fully differentiated in lung allografts, despite profound vascular rejection. Moreover, we demonstrate expression of the anti-apoptotic protein Bcl-2 in airway epithelial cells of acutely rejected lung allografts. These findings suggest that in addition to alloimmune responses, other stimuli may be required for the destruction of airway epithelial cells. Thus, the model of vascularized mouse lung transplantation may provide a new and more physiologic experimental tool to study the interaction between immune and nonimmune mechanisms affecting airway pathology in lung allografts.

  6. Local Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance Induction Protocol

    DTIC Science & Technology

    2016-10-01

    Chimerism Vascularized Composite Allograft Tolerance Induction Protocol PRINCIPAL INVESTIGATORS: Dr. Curtis L. Cetrulo CONTRACTING ORGANIZATION...Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance...tacrolimus, FK506, vascularized composite allografts , immune rejection, preclinical, transplant, nonhuman primate model, degradable polymer, tyrosine

  7. Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

    PubMed

    Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

    2015-08-01

    Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Evaluation of Digital PCR as a Technique for Monitoring Acute Rejection in Kidney Transplantation.

    PubMed

    Lee, Hyeseon; Park, Young-Mi; We, Yu-Mee; Han, Duck Jong; Seo, Jung-Woo; Moon, Haena; Lee, Yu-Ho; Kim, Yang-Gyun; Moon, Ju-Young; Lee, Sang-Ho; Lee, Jong-Keuk

    2017-03-01

    Early detection and proper management of kidney rejection are crucial for the long-term health of a transplant recipient. Recipients are normally monitored by serum creatinine measurement and sometimes with graft biopsies. Donor-derived cell-free deoxyribonucleic acid (cfDNA) in the recipient's plasma and/or urine may be a better indicator of acute rejection. We evaluated digital PCR (dPCR) as a system for monitoring graft status using single nucleotide polymorphism (SNP)-based detection of donor DNA in plasma or urine. We compared the detection abilities of the QX200, RainDrop, and QuantStudio 3D dPCR systems. The QX200 was the most accurate and sensitive. Plasma and/or urine samples were isolated from 34 kidney recipients at multiple time points after transplantation, and analyzed by dPCR using the QX200. We found that donor DNA was almost undetectable in plasma DNA samples, whereas a high percentage of donor DNA was measured in urine DNA samples, indicating that urine is a good source of cfDNA for patient monitoring. We found that at least 24% of the highly polymorphic SNPs used to identify individuals could also identify donor cfDNA in transplant patient samples. Our results further showed that autosomal, sex-specific, and mitochondrial SNPs were suitable markers for identifying donor cfDNA. Finally, we found that donor-derived cfDNA measurement by dPCR was not sufficient to predict a patient's clinical condition. Our results indicate that donor-derived cfDNA is not an accurate predictor of kidney status in kidney transplant patients.

  9. Electrical stimulation-evoked contractions blunt orthostatic hypotension in sub-acute spinal cord-injured individuals: two clinical case studies.

    PubMed

    Hamzaid, N A; Tean, L T; Davis, G M; Suhaimi, A; Hasnan, N

    2015-05-01

    Prospective study of two cases. To describe the effects of electrical stimulation (ES) therapy in the 4-week management of two sub-acute spinal cord-injured (SCI) individuals (C7 American Spinal Injury Association Impairment Scale (AIS) B and T9 AIS (B)). University Malaya Medical Centre, Kuala Lumpur, Malaysia. A diagnostic tilt-table test was conducted to confirm the presence of orthostatic hypotension (OH) based on the current clinical definitions. Following initial assessment, subjects underwent 4 weeks of ES therapy 4 times weekly for 1 h per day. Post-tests tilt table challenge, both with and without ES on their rectus abdominis, quadriceps, hamstrings and gastrocnemius muscles, was conducted at the end of the study (week 5). Subjects' blood pressures (BP) and heart rates (HR) were recorded every minute during pre-test and post-tests. Orthostatic symptoms, as well as the maximum tolerance time that the subjects could withstand head up tilt at 60°, were recorded. Subject A improved his orthostatic symptoms, but did not recover from clinically defined OH based on the 20-min duration requirement. With concurrent ES therapy, 60° head up tilt BP was 89/62 mm Hg compared with baseline BP of 115/71 mm Hg. Subject B fully recovered from OH demonstrated by BP of 105/71 mm Hg during the 60° head up tilt compared with baseline BP of 124/77 mm Hg. Both patients demonstrated longer tolerance time during head up tilt with concomitant ES (subject A: pre-test 4 min, post-test without ES 6 min, post-test with ES 12 min; subject B: pre-test 4 min, post-test without ES 28 min, post-test with ES 60 min). Weekly ES therapy had positive effect on OH management in sub-acute SCI individuals.

  10. Lower incidence of CMV infection and acute rejections with valganciclovir prophylaxis in lung transplant recipients

    PubMed Central

    2013-01-01

    Background Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS). Finding a strategy to prevent CMV infection is an important issue. Methods We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. Results For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival. For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). Conclusions A lower incidence of CMV infection/disease and acute rejections was

  11. MARS-MD: rejection based image domain material decomposition

    NASA Astrophysics Data System (ADS)

    Bateman, C. J.; Knight, D.; Brandwacht, B.; McMahon, J.; Healy, J.; Panta, R.; Aamir, R.; Rajendran, K.; Moghiseh, M.; Ramyar, M.; Rundle, D.; Bennett, J.; de Ruiter, N.; Smithies, D.; Bell, S. T.; Doesburg, R.; Chernoglazov, A.; Mandalika, V. B. H.; Walsh, M.; Shamshad, M.; Anjomrouz, M.; Atharifard, A.; Vanden Broeke, L.; Bheesette, S.; Kirkbride, T.; Anderson, N. G.; Gieseg, S. P.; Woodfield, T.; Renaud, P. F.; Butler, A. P. H.; Butler, P. H.

    2018-05-01

    This paper outlines image domain material decomposition algorithms that have been routinely used in MARS spectral CT systems. These algorithms (known collectively as MARS-MD) are based on a pragmatic heuristic for solving the under-determined problem where there are more materials than energy bins. This heuristic contains three parts: (1) splitting the problem into a number of possible sub-problems, each containing fewer materials; (2) solving each sub-problem; and (3) applying rejection criteria to eliminate all but one sub-problem's solution. An advantage of this process is that different constraints can be applied to each sub-problem if necessary. In addition, the result of this process is that solutions will be sparse in the material domain, which reduces crossover of signal between material images. Two algorithms based on this process are presented: the Segmentation variant, which uses segmented material classes to define each sub-problem; and the Angular Rejection variant, which defines the rejection criteria using the angle between reconstructed attenuation vectors.

  12. OKT3 treatment for steroid-resistant acute rejection in kidney transplantation.

    PubMed

    Sevmis, S; Emiroglu, R; Karakayali, F; Yagmurdur, M C; Dalgic, A; Moray, G; Haberal, M

    2005-09-01

    Orthoclone (OKT3, Ortho Biotech Inc, USA) monoclonal antilymphocyte antibody is a powerful T-cell-specific immunosuppressive agent. OKT3 has been used for induction therapy in kidney and liver transplantation, as well as to treat acute or steroid-resistant acute rejection episodes (ARE). This study was a retrospective analysis of 43 renal transplant recipients who developed steroid-resistant ARE and were treated with OKT3 between September 1994 and June 2004. The recipients were 36 men and 7 women of mean age 32.7 +/- 11.6 years (range, 19 to 48 years). The mean time from transplantation to OKT3 treatment was 7.2 +/- 6.7 months. Thirty-four episodes (79.1%) responded to OKT3 therapy with improved graft function, but the remaining 9 (20.9%) grafts did not respond. Among the 34 OKT3 responders, the mean serum creatinine decreased from 3.96 +/- 2.5 mg/dL to 2.45 +/- 1.77 mg/dL after treatment. Eleven (25.6%) of the 43 patients experienced minor side effects: fever, dyspnea, tachycardia, bradycardia. One patient (2.3%) developed acute pulmonary edema; one (2.3%), cytomegalovirus infection; and eight (18.6%), bacterial infections. The 1-, 3-, and 5-year graft survival rates for the 34 patients who responded to OKT3 therapy were 96%, 93%, and 85%, respectively. All patients are currently alive. The results indicate that OKT3 is a safe, effective treatment choice for steroid-resistant ARE in kidney transplantation.

  13. Capillary Thrombosis in the Skin: A Pathologic Hallmark of Severe/Chronic Rejection of Human Vascularized Composite Tissue Allografts?

    PubMed

    Kanitakis, Jean; Petruzzo, Palmina; Gazarian, Aram; Karayannopoulou, Georgia; Buron, Fannie; Dubois, Valérie; Thaunat, Olivier; Badet, Lionel; Morelon, Emmanuel

    2016-04-01

    Vascularized composite tissue allografts (VCA) can undergo rejection, manifesting pathologically with skin changes that form the basis of the Banff 2007 classification of VCA rejection. We have followed 10 human VCA recipients (7 with hand allografts, 3 with face allografts) for pathological signs of rejection. All of them developed episodes of acute rejection. Two patients with hand allografts presented in some of their skin biopsies an as yet unreported pathological finding in human VCA, consisting of capillary thromboses (CT) in the upper dermis. Capillary thrombosis was associated with other typical changes of grade II to III VCA rejection, namely, perivascular T cell infiltrates, but not with vascular C4d deposits (in formalin-fixed tissue). Clinically, the lesions presented as red or violaceous (lichenoid) cutaneous maculopapules. The first patient had several episodes of acute rejection during the 7-year follow-up. The second patient developed donor-specific antibodies; some months after CT were first observed, he developed chronic rejection leading to partial amputation of the allograft. Pathological examination of the skin showed graft vasculopathy and occasional C4d deposits in cutaneous capillaries. Capillary thrombosis seems to be a novel pathologic finding associated with human VCA rejection. Although its mechanism (immunologic vs nonimmunologic) remains unclear, this finding could carry an unfavorable prognostic significance, prompting close monitoring of the patients for severe/chronic rejection.

  14. [Prevalence and characteristics of acute coronary syndromes in a sub-Saharan Africa population].

    PubMed

    N'Guetta, R; Yao, H; Ekou, A; N'Cho-Mottoh, M P; Angoran, I; Tano, M; Konin, C; Coulibaly, I; Anzouan-Kacou, J B; Seka, R; Adoh, A M

    2016-04-01

    To assess prevalence, characteristics and management of acute coronary syndromes in sub-Saharan Africa population. Prospective survey from January, 2010 to December, 2013, carried out among patients aged 18 years old, admitted to intensive care unit of Abidjan Heart Institute for acute coronary syndrome (ACS). Four hundred and twenty-five (425) patients were enrolled in this study. Prevalence of ACS was 13.5%. Mean age was 55.4±11 years. Clinical presentation was predominantly ST-segment elevation myocardial infarction (STEMI) in 71.5% of subjects, non-ST-segment elevation acute coronary syndrome (NSTE-ACS) accounted for 28.5%. Two hundred and eighty patients (65.9%) were transferred by unsafe transportation. Among the 89 patients admitted within 12hours of the onset of symptoms, primary percutaneous coronary intervention was performed in 20 patients (22.5%), or 6.6% of STEMI as a whole. Twenty-five patients (8.2%) received fibrinolytic therapy with alteplase. In-hospital death rate was 10%. The prevalence of acute coronary syndromes is increasing in sub-Saharan Africa. Excessive delays of admission and limited technical facilities are the major difficulties of their management in our regions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Artificial intelligence techniques: predicting necessity for biopsy in renal transplant recipients suspected of acute cellular rejection or nephrotoxicity.

    PubMed

    Hummel, A D; Maciel, R F; Sousa, F S; Cohrs, F M; Falcão, A E J; Teixeira, F; Baptista, R; Mancini, F; da Costa, T M; Alves, D; Rodrigues, R G D S; Miranda, R; Pisa, I T

    2011-05-01

    The gold standard for nephrotoxicity and acute cellular rejection (ACR) is a biopsy, an invasive and expensive procedure. More efficient strategies to screen patients for biopsy are important from the clinical and financial points of view. The aim of this study was to evaluate various artificial intelligence techniques to screen for the need for a biopsy among patients suspected of nephrotoxicity or ACR during the first year after renal transplantation. We used classifiers like artificial neural networks (ANN), support vector machines (SVM), and Bayesian inference (BI) to indicate if the clinical course of the event suggestive of the need for a biopsy. Each classifier was evaluated by values of sensitivity and area under the ROC curve (AUC) for each of the classifiers. The technique that showed the best sensitivity value as an indicator for biopsy was SVM with an AUC of 0.79 and an accuracy rate of 79.86%. The results were better than those described in previous works. The accuracy for an indication of biopsy screening was efficient enough to become useful in clinical practice. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-01-01

    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. 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. 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. 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.

  17. 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.

  18. Evaluation of serum sCD30 in renal transplantation patients with and without acute rejection.

    PubMed

    Cervelli, C; Fontecchio, G; Scimitarra, M; Azzarone, R; Famulari, A; Pisani, F; Battistoni, C; Di Iulio, B; Fracassi, D; Scarnecchia, M A; Papola, F

    2009-05-01

    Despite new immunosuppressive approaches, acute rejection episodes (ARE) are still a major cause of early kidney dysfunction with a negative impact on long-term allograft survival. Noninvasive markers able to identify renal ARE earlier than creatinine measurement include sCD30. We sought to establish whether circulating levels of sCD30 in pretransplantation and posttransplantation periods were of clinical relevance to avoid graft damage. Quantitative detection of serum sCD30 was performed using an enzyme-linked immunosorbent assay. Our results demonstrated that the mean concentrations of sCD30 were significantly higher in the sera of renal transplant recipients with ARE (30.04 U/mL) and in uremic patients on the waiting list (37.7 U/mL) compared with healthy controls (HC; 9.44 U/mL), but not nonrejecting patients (12.01 U/mL). Statistical analysis revealed a strong association between high sCD30 levels in posttransplantation sera and ARE risk. This study suggested that sCD30 levels were a reliable predictor of ARE among deceased-donor kidney recipients.

  19. Histological long-term outcomes from acute antibody-mediated rejection following ABO-compatible liver transplantation.

    PubMed

    Del Bello, Arnaud; Danjoux, Marie; Congy-Jolivet, Nicolas; Lavayssière, Laurence; Esposito, Laure; Muscari, Fabrice; Kamar, Nassim

    2017-04-01

    Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known. Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination. Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03). In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  20. Anti-IL-17 therapy restricts and reverses late-term corneal allo-rejection

    PubMed Central

    Yin, Xiao-Tang; Zobell, Stephanie; Jarosz, Jason G.; Stuart, Patrick M.

    2015-01-01

    Corneal allograft rejection has been described as a Th1-mediated process involving IFN-γ production. However, recent evidence has also implicated IL-17 as being involved during acute corneal allograft responses. Our data supports those that maintain that IL-17 is involved in early acute corneal allograft acceptance. However, we decided to extend these studies to include a later phase of rejection in which there is a peak of IL-17 production that is >15 fold higher than seen during acute rejection that occurs >45 days post-engraftment at the onset of late-term rejection. We demonstrate that neutralizing IL-17A at this time significantly reduced corneal graft rejection. Surprisingly, when corneal grafts that are undergoing this later phase of rejection are treated with anti-IL17A there is a reversal of both opacity and neovascularization. When compared to the early phase of rejection, the cellular infiltrate is significantly less with a greatly reduced presence of Gr-1+ neutrophils with a relative increase in CD4+ T cells and macrophages. We went on to identify that the cells expressing IL-17 were CD4+ IL-17+ T cells and somewhat surprisingly, IL-17+ F4/80+ macrophages within the rejecting corneal allografts. Taken together, these findings describe a distinct late phase of corneal allograft rejection which is likely mediated by Th17 cells and that therapeutic neutralization of IL-17A reverses this rejection. This further suggests that IL-17 might serve as an excellent therapeutic target to reduce this form of corneal allograft rejection. PMID:25754737

  1. Betaine in sub-acute and sub-chronic rat studies.

    PubMed

    Hayes, K C; Pronczuk, Andrzej; Cook, Melvyn W; Robbins, Mark C

    2003-12-01

    To evaluate the sub-acute and sub-chronic effect of large doses of betaine, this trimethyl glycine compound was fed to rats. Initial studies at BIBRA in the UK evaluated intakes of 0, 1, 2, and 5% betaine added to a maintenance chow designed for use in toxicology studies. Male and female Sprague-Dawley rats were followed for up to 90 days. No toxicity occurred, but at higher betaine intakes several serum chemistries were altered slightly, the MCV, MCH, and MCHC of red cells were reduced, and hepatocytes developed fatty droplets in direct proportion to betaine intake. Females were more affected than males. In a second study to assess reversibility in females, betaine effects were induced for 28 days, followed by a 28 day betaine-free period. All perturbations, except the reduced MCV and MCH, were reversed. As a follow up to BIBRA investigations, both 28 and 90 day feeding trials were conducted at Brandeis University using a rat chow with higher levels of energy, protein, and fat, with betaine added at 0, 0.5, 0.75, 1.0 and 5.0% of the diet. A similar broad range of clinical chemistries and physiological parameters were monitored, and hepatic lipid droplets were investigated in more detail. Liver lipid was actually reduced by betaine, and no significant adverse effects of clinical importance resulted from any dose. However, the MCV was again reduced at 5% betaine in the 28 day study. By 90 days all parameters were normal and comparable to controls. Based on these collective data, it was concluded that even at these high doses, betaine is nontoxic. Differences observed between the BIBRA and Brandeis studies were attributed to differences in the dietary formulations. Significant betainexdietxgrowth interactions were thought to reflect primary disparities in protein and energy concentrations, more than the addition of betaine per se.

  2. Practices for Identifying and Rejecting Hemolyzed Specimens Are Highly Variable in Clinical Laboratories.

    PubMed

    Howanitz, Peter J; Lehman, Christopher M; Jones, Bruce A; Meier, Frederick A; Horowitz, Gary L

    2015-08-01

    Hemolysis is an important clinical laboratory quality attribute that influences result reliability. To determine hemolysis identification and rejection practices occurring in clinical laboratories. We used the College of American Pathologists Survey program to distribute a Q-Probes-type questionnaire about hemolysis practices to Chemistry Survey participants. Of 3495 participants sent the questionnaire, 846 (24%) responded. In 71% of 772 laboratories, the hemolysis rate was less than 3.0%, whereas in 5%, it was 6.0% or greater. A visual scale, an instrument scale, and combination of visual and instrument scales were used to identify hemolysis in 48%, 11%, and 41% of laboratories, respectively. A picture of the hemolysis level was used as an aid to technologists' visual interpretation of hemolysis levels in 40% of laboratories. In 7.0% of laboratories, all hemolyzed specimens were rejected; in 4% of laboratories, no hemolyzed specimens were rejected; and in 88% of laboratories, some specimens were rejected depending on hemolysis levels. Participants used 69 different terms to describe hemolysis scales, with 21 terms used in more than 10 laboratories. Slight and moderate were the terms used most commonly. Of 16 different cutoffs used to reject hemolyzed specimens, moderate was the most common, occurring in 30% of laboratories. For whole blood electrolyte measurements performed in 86 laboratories, 57% did not evaluate the presence of hemolysis, but for those that did, the most common practice in 21 laboratories (24%) was centrifuging and visually determining the presence of hemolysis in all specimens. Hemolysis practices vary widely. Standard assessment and consistent reporting are the first steps in reducing interlaboratory variability among results.

  3. Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

    PubMed Central

    Pascual, Julio; Samaniego, Milagros D.; Torrealba, José R.; Odorico, Jon S.; Djamali, Arjang; Becker, Yolanda T.; Voss, Barbara; Leverson, Glen E.; Knechtle, Stuart J.; Sollinger, Hans W.; Pirsch, John D.

    2008-01-01

    The prevalence, risk factors, and outcome of antibody-mediated rejection (AMR) of the kidney after simultaneous pancreas-kidney transplantation are unknown. In 136 simultaneous pancreas-kidney recipients who were followed for an average of 3.1 yr, 21 episodes of AMR of the kidney allograft were identified. Eight episodes occurred early (≤90 d) after transplantation, and 13 occurred later. Histologic evidence of concomitant acute cellular rejection was noted in 12 cases; the other nine had evidence only of humoral rejection. In 13 cases, clinical rejection of the pancreas was diagnosed simultaneously, and two of these were biopsy proven and were positive for C4d immunostaining. Multivariate analysis identified only one significant risk factor: Female patients were three times more likely to experience AMR. Nearly all early episodes resolved with treatment and did not predict graft loss, but multivariate Cox models revealed that late AMR episodes more than tripled the risk for kidney and pancreas graft loss; therefore, new strategies are needed to prevent and to treat late AMR in simultaneous pancreas-kidney transplant recipients. PMID:18235091

  4. The perspective of allied health staff on the role of nurses in sub-acute care.

    PubMed

    Digby, Robin; Bolster, Danielle; Perta, Andrew; Bucknall, Tracey K

    2018-06-12

    To explore allied health staff perceptions on the role of nurses in sub-acute care wards. A consequence of earlier discharge from acute hospitals is higher acuity of patients in sub-acute care. The impact on nurses' roles and required skill mix remains unknown. Similarly, nurses' integration into the rehabilitation team is ambiguous. Descriptive qualitative inquiry. Semi-structured interviews conducted with 14 allied health staff from one sub-acute care facility in Melbourne, Australia. Interviews were audio-recorded and transcribed verbatim. Analysis using the framework approach. Three main themes were evident: 1) The changing context of care: patient acuity, rapid patient discharge and out-dated buildings influenced care, 2) Generalist as opposed to specialist rehabilitation nurses: a divide between traditional nursing roles of clinical and personal care and a specialist rehabilitation role, and 3) Interdisciplinary relations and communication demonstrated lack of respect for nurses and integrating holistic care into everyday routines. Allied health staff had limited understanding of nurses' role in sub-acute care, and expectations varied. Power relationships appeared to hamper teamwork. Failure to include nurses in team discussions and decision-making could hinder patient outcomes. Progressing patients to levels of independence involves both integrating rehabilitation into activities of daily living with nurses and therapy-based sessions. Promotion of the incorporation of nursing input into patient rehabilitation is needed with both nurses and allied health staff. Lack of understanding of the nurses' role contributes to lack of respect for the nursing contribution to rehabilitation. Nurses have a key role in rehabilitation sometimes impeded by poor teamwork with allied health staff. Processes in sub-acute care wards need examination to facilitate more effective team practices inclusive of nurses. Progressing patients' independence in rehabilitation units

  5. Safety evaluation of tangeretin and the effect of using emulsion-based delivery system: Oral acute and 28-day sub-acute toxicity study using mice.

    PubMed

    Ting, Yuwen; Chiou, Yi-Shiou; Jiang, Yike; Pan, Min-Hsiung; Lin, Zhengyu; Huang, Qingrong

    2015-08-01

    Polymethoxyflavones, found widely in the peel of citrus fruits, is an emerging group of bioactive compounds with wide arrays of disease prevention functionalities. To understand the potential oral toxicity, tangeretin, being one of the most abundant polymethoxyflavones from natural sources, was used as model compound for the safety evaluation. Acute oral toxicity study was conducted using both male and female mice giving 1000, 2000, or 3000mg/kgbody weight (bw) of tangeretin in oil suspension from single gavage administration. No evidence of death was observed during 14-day post-administration period. Alterations of the hepatic cell and clinical chemistry profile increased dose dependently and exhibited distinct injury recovery pattern among different sexes. To determine the potential safety concern related to emulsification, the sub-acute toxicity of tangeretin in emulsion was evaluated and compared with un-processed oil suspension when conducting the sub-acute toxicity study over 28days. In the sub-acute study, emulsion system did not induce a significant increase of toxicity response. However, the daily low-dose application of tangeretin showed U-shaped dose-response pattern in regard to hepatic alteration. The result from this study can serve as a good safety reference for future application of polymethoxyflavone as a functional ingredient in food. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia

    PubMed Central

    Quintana-Díaz, Manuel; Fabra-Cadenas, Sara; Gómez-Ramírez, Susana; Martínez-Virto, Ana; García-Erce, José A.; Muñoz, Manuel

    2016-01-01

    Background Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. Materials and methods From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500–1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. Results Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000–2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1–3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. Discussion Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED. PMID:26674819

  7. A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia.

    PubMed

    Quintana-Díaz, Manuel; Fabra-Cadenas, Sara; Gómez-Ramírez, Susana; Martínez-Virto, Ana; García-Erce, José A; Muñoz, Manuel

    2016-03-01

    Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500-1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000-2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1-3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED.

  8. Acute and sub-acute toxicological assessment of the aqueous seed extract of Persea americana mill (Lauraceae) in rats.

    PubMed

    Ozolua, Raymond I; Anaka, Ogochukwu N; Okpo, Stephen O; Idogun, Sylvester E

    2009-07-03

    The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD(50)) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD(50) could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.

  9. Evaluation of pre- and posttransplantation serum interferon-gamma and soluble CD30 for predicting liver allograft rejection.

    PubMed

    Kim, K H; Oh, E-J; Jung, E-S; Park, Y-J; Choi, J Y; Kim, D-G; Lee, K Y; Kang, C S

    2006-06-01

    The aim of the present study was to identify whether the serum interferon-gamma (IFNgamma), a Th1 cytokine, or soluble CD30 (sCD30), a marker for activation of Th2 cytokine-producing T cells, predict acute cellular rejection episodes among liver graft patients. Pretransplant and posttransplant sera from 32 living donor liver transplant recipients obtained on days 1, 3, and 7 after surgery were tested for serum IFNgamma and sCD30 concentrations using commercial enzyme-linked immunosorbent assay kits. Recipients with an acute rejection episode (ARE) (n=14) displayed significantly higher IFNgamma concentrations pretransplant than did the patients with no ARE (n=18) (P<.05). The pretransplant serum levels of sCD30 were not different between the non-ARE and ARE groups. However, in comparison with the non-ARE group, who showed steadily decreasing serum sCD30 levels after transplantation, 12 among the 14 patients in the ARE group showed increasing sCD30 levels from day 1 to day 3 after transplantation (P<.05). These results suggest that the sCD30 increment during the early period after liver transplantation affects the immune response of rejection. This observation emphasizes the clinical relevance of serum sCD30, in addition to serum IFNgamma, as predictive markers for acute liver graft rejection.

  10. Impact of Banff borderline acute rejection among renal allograft recipients.

    PubMed

    Matoza, J R A; Danguilan, R A; Chicano, S

    2008-09-01

    This study was performed to determine the incidence, treatment, and outcomes of Banff borderline acute rejection (AR) among renal transplant recipients. We reviewed the courses of adult kidney transplant recipients with borderline AR on clinically indicated biopsies performed at our center from January 2003 to July 2006. Patients with complete transplant records and serum creatinine values at 6 and 12 months were included in this study. The primary outcome measures were serum creatinine values at 1 to 2 weeks after treatment, and at 6 and 12 months after graft biopsy. Among 428 renal graft biopsies, borderline AR was observed in 100 cases (23%). Patients were maintained on the same immunosuppression. The 86 who had complete data were included in the study. Seventy-eight percent of the patients received treatment with 3 days of methylprednisolone, while 22% were untreated. Mean serum creatinine values in the treated group were 2.9 +/- 1.0, 2.6 +/- 2.5, and 3.0 +/- 2.9 mg/dL at the time of biopsy, and at 6 and 12 months thereafter, respectively. In the untreated group, mean serum creatinine values were 2.2 +/- 1.0, 1.9 +/- 0.8, and 2.3 +/- 1.2 mg/dL during biopsy, and at 6 and 12 months thereafter, respectively. There was no significant difference in the serum creatinine at any of the measured time points between the 2 groups. Twelve patients had repeat renal graft biopsies which showed AR (6%), chronic allograft nephropathy (2.4%), and borderline changes (3.8%). Nine of the patients in the treated group eventually developed graft loss. Patients with borderline AR showed a progressive increase in serum creatinine over time. They should be followed closely; immunosuppression may need to be intensified.

  11. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models.

    PubMed

    Adamcakova-Dodd, Andrea; Stebounova, Larissa V; Kim, Jong Sung; Vorrink, Sabine U; Ault, Andrew P; O'Shaughnessy, Patrick T; Grassian, Vicki H; Thorne, Peter S

    2014-04-01

    Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity

  12. Feasibility of incorporating functionally relevant virtual rehabilitation in sub-acute stroke care: perception of patients and clinicians.

    PubMed

    Demers, Marika; Chan Chun Kong, Daniel; Levin, Mindy F

    2018-03-11

    To determine user satisfaction and safety of incorporating a low-cost virtual rehabilitation intervention as an adjunctive therapeutic option for cognitive-motor upper limb rehabilitation in individuals with sub-acute stroke. A low-cost upper limb virtual rehabilitation application incorporating realistic functionally-relevant unimanual and bimanual tasks, specifically designed for cognitive-motor rehabilitation was developed for patients with sub-acute stroke. Clinicians and individuals with stroke interacted with the intervention for 15-20 or 20-45 minutes, respectively. The study had a mixed-methods convergent parallel design that included a focus group interview with clinicians working in a stroke program and semi-structured interviews and standardized assessments (Borg Perceived Exertion Scale, Short Feedback Questionnaire) for participants with sub-acute stroke undergoing rehabilitation. The occurrence of adverse events was also noted. Three main themes emerged from the clinician focus group and patient interviews: Perceived usefulness in rehabilitation, satisfaction with the virtual reality intervention and aspects to improve. All clinicians and the majority of participants with stroke were highly satisfied with the intervention and perceived its usefulness to decrease arm motor impairment during functional tasks. No participants experienced major adverse events. Incorporation of this type of functional activity game-based virtual reality intervention in the sub-acute phase of rehabilitation represents a way to transfer skills learned early in the clinical setting to real world situations. This type of intervention may lead to better integration of the upper limb into everyday activities. Implications for Rehabilitation • Use of a cognitive-motor low-cost virtual reality intervention designed to remediate arm motor impairments in sub-acute stroke is feasible, safe and perceived as useful by therapists and patients for stroke rehabilitation.

  13. The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes.

    PubMed

    Wu, Kaiyin; Budde, Klemens; Lu, Huber; Schmidt, Danilo; Liefeldt, Lutz; Glander, Petra; Neumayer, Hans Helmut; Rudolph, Birgit

    2014-06-15

    It is unclear if the severity or the timing of acute cellular rejection (ACR) defined by Banff classification 2009 is associated with graft survival. Borderline changes, TCMR I (interstitial rejection), and TCMR II/III (vascular rejection) were defined as low, moderate, and high ACR severity, respectively. Approximately 270 patients who had at least one episode of ACR were enrolled, 270 biopsies were chosen which showed the highest ACR severity of each patient and were negative for donor-specific antibodies (DSA), C4d, and microcirculation changes (MC). Six months were used as the cutoff to define early and late ACR; 370 patients without biopsy posttransplantation were recruited in the control group. Up to 8-year posttransplantation, death-censored graft survival (DCGS) rates of control, borderline, TCMR I, and TCMR II/III groups were 97.6%, 93.3%, 79.6%, and 73.6% (log rank test, P<0.001); the control group had significantly higher DCGS rate than the three ACR groups (each pairwise comparison yields P<0.05). The DCGS rate of late ACR was significantly lower compared with early ACR (63.6% vs. 87.4%, P<0.001). Intimal arteritis (Banff v-lesion) was an independent histologic risk factor correlated with long-term graft loss regardless of the timing of ACR. The v-lesions with minimal or high-grade tubulitis displayed similar graft survival (72.7% vs. 72.9%, P=0.96). All types of ACR affect long-term graft survival. Vascular or late ACR predict poorer graft survival; the extent of tubulointerstitial inflammation (TI) is of no prognostic significance for vascular rejection.

  14. Soluble CD30 in renal transplant recipients: is it a good biomarker to predict rejection?

    PubMed

    Azarpira, Negar; Aghdaie, Mahdokht Hosein; Malekpour, Zahra

    2010-01-01

    It has been suggested that the serum soluble CD30 (sCD30) level may be a poten-tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum samples. Ninety-nine patients were divided in two separate groups: Group A in whom sample collection was done one day before transplantation and Group B where sample collection was done five days after transplantation. Younger recipients (aged less than 20 years) had higher sCD30 levels (P= 0.02). There was neither significant difference in the incidence of acute rejection nor incomplete response rate after anti rejection therapy in relation to pre transplant or post transplant sCD30. We could not find a significantly inferior graft survival rate in the high sCD30 group. In conclusion, younger patients had higher sCD30 concentrations however no correlation existed between the serum concentrations and occurrence of rejection episodes or graft survival.

  15. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    PubMed Central

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  16. Soluble CD30 and ELISA-detected human leukocyte antigen antibodies for the prediction of acute rejection in pediatric renal transplant recipients.

    PubMed

    Billing, Heiko; Sander, Anja; Süsal, Caner; Ovens, Jörg; Feneberg, Reinhard; Höcker, Britta; Vondrak, Karel; Grenda, Ryszard; Friman, Stybjorn; Milford, David V; Lucan, Mihai; Opelz, Gerhard; Tönshoff, Burkhard

    2013-03-01

    Biomarker-based post-transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well-controlled prospective randomized trial was analyzed pre- and post-transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T-cell reactivity, and anti-human leukocyte antigen (anti-HLA) antibody reactivity, a biomarker for B-cell activation. A sCD30 concentration ≥40.3 U/ml on day 14 was able to discriminate between patients with or without biopsy-proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut-off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut-off (P = 0.004). For pre- and post-transplant anti-HLA class II reactivities by enzyme-linked immunosorbent assay, a cut-off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti-HLA reactivities. An increased post-transplant sCD30 serum concentration and positive pre- and post-transplant anti-HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG-506-02-43). © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

  17. Acute Cellular Rejection in ABO-Incompatible Renal Transplant Recipients Receiving Rituximab Is Associated with Delayed-Onset Neutropenia.

    PubMed

    Uchida, Junji; Iwai, Tomoaki; Nishide, Shunji; Kabei, Kazuya; Kuwabara, Nobuyuki; Yamasaki, Takeshi; Naganuma, Toshihide; Kumada, Norihiko; Takemoto, Yoshiaki; Nakatani, Tatsuya

    2017-07-25

    BACKGROUND Rituximab induces long-lasting B cell depletion in the peripheral blood and increases the levels of proinflammatory cytokines associated with regulatory B cell depletion. Previous reports showed that B cell-related cytokine release after administration of rituximab may induce acute cellular rejection (ACR) and delayed-onset neutropenia. The present study was conducted to investigate the correlation between acute rejection and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. MATERIAL AND METHODS From June 2006 to July 2015, 47 patients with chronic renal failure received ABO-incompatible renal transplant with rituximab induction at Osaka City University Hospital. All 47 patients underwent plasmapheresis due to removal of anti-A/B antibodies and administration of rituximab, and their transplants were carried out successfully. We investigated the correlation between ACR and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. RESULTS Fourteen patients (29.8%) experienced ACR (group A), and 33 recipients did not develop ACR (group B). The frequency of delayed-onset neutropenia was higher in group A than in group B (p=0.0503). Multivariate logistic regression analysis revealed that the frequency of ACR correlated significantly with the prevalence of delayed-onset neutropenia. CONCLUSIONS Our results indicated that ACR in ABO-incompatible renal transplant recipients receiving rituximab was associated with delayed-onset neutropenia.

  18. Identification of patients at risk of acute rejection by pretransplantation and posttransplantation monitoring of soluble CD30 levels in kidney transplantation.

    PubMed

    Sengul, Sule; Keven, Kenan; Gormez, Ulku; Kutlay, Sim; Erturk, Sehsuvar; Erbay, Bulent

    2006-04-27

    In this study, we investigated the impact of pre- and posttransplantation sCD30 monitoring on early (<6 months) acute rejection (AR) risk and analyzed the effect of different immunosuppressive regimens on posttransplantation sCD30 levels in kidney recipients. Fifty patients receiving kidney allograft and 10 healthy donors were included in this retrospective cohort study. Eight patients developed biopsy-proven AR (19%). In pretransplantation samples, patients showed a significantly higher sCD30 than healthy controls. The pretransplantation and posttransplantation (day-15) sCD30 levels were significantly elevated in rejecting patients compared to non-rejecting patients. No significant differences among immunosuppressive regimens were found in posttransplantation sCD30 levels. High pretransplantation and posttransplantation (day 15) sCD30 levels are associated with increased risk of early AR, and sCD30 can be another tool to evaluate immunological risk prior to kidney transplantation. There was no difference in immunosuppressive regimens used in this study on posttransplantation sCD30 levels at the first month.

  19. Kidney Transplant Rejection and Tissue Injury by Gene Profiling of Biopsies and Peripheral Blood Lymphocytes

    PubMed Central

    Flechner, Stuart M.; Kurian, Sunil M.; Head, Steven R.; Sharp, Starlette M.; Whisenant, Thomas C.; Zhang, Jie; Chismar, Jeffrey D.; Horvath, Steve; Mondala, Tony; Gilmartin, Timothy; Cook, Daniel J.; Kay, Steven A.; Walker, John R.; Salomon, Daniel R.

    2007-01-01

    A major challenge for kidney transplantation is balancing the need for immunosuppression to prevent rejection, while minimizing drug-induced toxicities. We used DNA microarrays (HG-U95Av2 GeneChips, Affymetrix) to determine gene expression profiles for kidney biopsies and peripheral blood lymphocytes (PBLs) in transplant patients including normal donor kidneys, well-functioning transplants without rejection, kidneys undergoing acute rejection, and transplants with renal dysfunction without rejection. We developed a data analysis schema based on expression signal determination, class comparison and prediction, hierarchical clustering, statistical power analysis and real-time quantitative PCR validation. We identified distinct gene expression signatures for both biopsies and PBLs that correlated significantly with each of the different classes of transplant patients. This is the most complete report to date using commercial arrays to identify unique expression signatures in transplant biopsies distinguishing acute rejection, acute dysfunction without rejection and well-functioning transplants with no rejection history. We demonstrate for the first time the successful application of high density DNA chip analysis of PBL as a diagnostic tool for transplantation. The significance of these results, if validated in a multicenter prospective trial, would be the establishment of a metric based on gene expression signatures for monitoring the immune status and immunosuppression of transplanted patients. PMID:15307835

  20. Fall risk as a function of time after admission to sub-acute geriatric hospital units.

    PubMed

    Rapp, Kilian; Ravindren, Johannes; Becker, Clemens; Lindemann, Ulrich; Jaensch, Andrea; Klenk, Jochen

    2016-10-07

    There is evidence about time-dependent fracture rates in different settings and situations. Lacking are data about underlying time-dependent fall risk patterns. The objective of the study was to analyse fall rates as a function of time after admission to sub-acute hospital units and to evaluate the time-dependent impact of clinical factors at baseline on fall risk. This retrospective cohort study used data of 5,255 patients admitted to sub-acute units in a geriatric rehabilitation clinic in Germany between 2010 and 2014. Falls, personal characteristics and functional status at admission were extracted from the hospital information system. The rehabilitation stay was divided in 3-day time-intervals. The fall rate was calculated for each time-interval in all patients combined and in subgroups of patients. To analyse the influence of covariates on fall risk over time multivariate negative binomial regression models were applied for each of 5 time-intervals. The overall fall rate was 10.2 falls/1,000 person-days with highest fall risks during the first week and decreasing risks within the following weeks. A particularly pronounced risk pattern with high fall risks during the first days and decreasing risks thereafter was observed in men, disoriented people, and people with a low functional status or impaired cognition. In disoriented patients, for example, the fall rate decreased from 24.6 falls/1,000 person-days in day 2-4 to about 13 falls/1,000 person-days 2 weeks later. The incidence rate ratio of baseline characteristics changed also over time. Fall risk differs considerably over time during sub-acute hospitalisation. The strongest association between time and fall risk was observed in functionally limited patients with high risks during the first days after admission and declining risks thereafter. This should be considered in the planning and application of fall prevention measures.

  1. Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

    PubMed

    Lo, Wai-Kit; Goldberg, Hilary J; Boukedes, Steve; Burakoff, Robert; Chan, Walter W

    2018-02-01

    Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

  2. 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. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Antitumor activity of nivolumab on hemodialysis after renal allograft rejection.

    PubMed

    Ong, Michael; Ibrahim, Andrea Marie; Bourassa-Blanchette, Samuel; Canil, Christina; Fairhead, Todd; Knoll, Greg

    2016-01-01

    Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer. We illustrate the outcomes of a 63 year-old type I diabetic female patient who developed pulmonary metastatic, BRAF wild-type cutaneous melanoma 10 years after renal transplantation. After downward titration of the patient's immunosuppressive medications and extensive multidisciplinary review, she was treated with nivolumab in the first-line setting. Within 1 week of administration, the patient experienced acute renal allograft rejection, renal failure and concurrent diabetic ketoacidosis due to steroid therapy. Allograft function did not return, but patient made a full clinical recovery after being placed on hemodialysis. Subsequently, the patient had clinical disease progression off therapy and required re-challenge with nivolumab on hemodialysis, resulting in ongoing clinical and radiographic response. This case illustrates multiple practical challenges and dangers of administering anti-PD1 immune checkpoint inhibitors to patients with solid-organ transplantation including need for titration of immunosuppressive medications, risks of allograft rejection, and treatment during hemodialysis.

  4. Peripheral blood sampling for the detection of allograft rejection: biomarker identification and validation.

    PubMed

    Heidt, Sebastiaan; San Segundo, David; Shankar, Sushma; Mittal, Shruti; Muthusamy, Anand S R; Friend, Peter J; Fuggle, Susan V; Wood, Kathryn J

    2011-07-15

    Currently, acute allograft rejection can only be detected reliably by deterioration of graft function confirmed by allograft biopsy. A huge drawback of this method of diagnosis is that substantial organ damage has already taken place at the time that rejection is diagnosed. Discovering and validating noninvasive biomarkers that predict acute rejection, and chronic allograft dysfunction, is of great importance. Many studies have investigated changes in the peripheral blood in an attempt to find biomarkers that reflect changes in the graft directly or indirectly. Herein, we will review the promises and limitations of the peripheral blood biomarkers that have been described in the literature so far.

  5. Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats.

    PubMed

    Al-Afifi, Nashwan Abdullah; Alabsi, Aied Mohammed; Bakri, Marina Mohd; Ramanathan, Anand

    2018-02-05

    Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. This study demonstrates tolerability of DC

  6. Perturbations in the Urinary Exosome in Transplant Rejection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sigdel, Tara K.; NG, Yolanda; Lee, Sangho

    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. Themore » 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

  7. Innate NK cells and macrophages recognize and reject allogeneic nonself in vivo via different mechanisms.

    PubMed

    Liu, Wentao; Xiao, Xiang; Demirci, Gulcin; Madsen, Joren; Li, Xian C

    2012-03-15

    Both innate and adaptive immune cells are involved in the allograft response. But how the innate immune cells respond to allotransplants remains poorly defined. In the current study, we examined the roles of NK cells and macrophages in recognizing and rejecting allogeneic cells in vivo. We found that in naive mice NK cells are the primary effector cells in the killing of allogeneic cells via "missing self" recognition. However, in alloantigen-presensitized mice, NK cells are dispensable. Instead, macrophages become alloreactive and readily recognize and reject allogeneic nonself. This effect requires help from activated CD4(+) T cells and involves CD40/CD40L engagement, because blocking CD40/CD40L interactions prevents macrophage-mediated rejection of allogeneic cells. Conversely, actively stimulating CD40 triggers macrophage-mediated rejection in the absence of CD4(+) T cells. Importantly, alloantigen-primed and CD4(+) T cell-helped macrophages (licensed macrophages) exhibit potent regulatory function in vivo in an acute graft-versus-host disease model. Together, our data uncover an important role for macrophages in the alloimmune response and may have important clinical implications.

  8. 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

  9. Rejection is less common in children undergoing liver transplantation for hepatoblastoma.

    PubMed

    Ruth, N D; Kelly, D; Sharif, K; Morland, B; Lloyd, C; McKiernan, P J

    2014-02-01

    To compare the incidence of acute histologically proven rejection in children who have had a liver transplant for hepatoblastoma with a control group of children transplanted for biliary atresia (EHBA). A retrospective case notes based study was performed. Twenty patients were identified with hepatoblastoma who were transplanted at a single unit between 1991 and 2008. These were matched as closely as possible for age, gender, year of transplant and type of immunosuppression used to the control group transplanted for biliary atresia (n = 60). There was a significant decrease in rate of acute rejection as assessed by the rejection activity index (RAI) in the hepatoblastoma group (75% vs. 50%, respectively, p < 0.04). Chronic rejection was rare in both groups, but twice as common in the biliary atresia group. Equal levels of immunosuppression were achieved in both groups. Renal function was noted to be reduced one yr post-transplant in both groups, as previously reported. A modified immunosuppression regimen could be considered in children with hepatoblastoma undergoing liver transplantation. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Banff schema for grading pancreas allograft rejection: working proposal by a multi-disciplinary international consensus panel.

    PubMed

    Drachenberg, C B; Odorico, J; Demetris, A J; Arend, L; Bajema, I M; Bruijn, J A; Cantarovich, D; Cathro, H P; Chapman, J; Dimosthenous, K; Fyfe-Kirschner, B; Gaber, L; Gaber, O; Goldberg, J; Honsová, E; Iskandar, S S; Klassen, D K; Nankivell, B; Papadimitriou, J C; Racusen, L C; Randhawa, P; Reinholt, F P; Renaudin, K; Revelo, P P; Ruiz, P; Torrealba, J R; Vazquez-Martul, E; Voska, L; Stratta, R; Bartlett, S T; Sutherland, D E R

    2008-06-01

    Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.

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

    PubMed

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

    2013-01-01

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

  12. Level of soluble CD30 after kidney transplantation correlates with acute rejection episodes.

    PubMed

    Yang, J L; Hao, H J; Zhang, B; Liu, Y X; Chen, S; Na, Y Q

    2008-12-01

    Measurement of soluble CD30 (sCD30) levels may predict acute rejection episodes (ARE). To explore the value of sCD30 after transplantation, we tested serum sCD30 levels in 58 kidney transplant cases at 1 day before and 7 and 28 days after transplantation by enzyme-linked immunosorbent assay (ELISA). The incidences of ARE after kidney transplantation were recorded simultaneously. Meanwhile, 31 healthy individuals were selected as a control group. The results showed a relationship between sCD30 level in serum before kidney transplantation and the incidence of ARE. However, the relationship was more significant between serum sCD30 levels at day 7 after kidney transplantation and the incidence of ARE. There was no obvious relationship between serum sCD30 levels at day 28 after kidney transplantation and the incidence of ARE. These results suggested that the level of sCD30 at day 7 posttransplantation provides valuable data to predict ARE.

  13. Safety assessment of hydroethanolic rambutan rind extract: acute and sub-chronic toxicity studies.

    PubMed

    Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

    2014-10-01

    This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) andalanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE.

  14. 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

  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. The outcast-lash-out effect in youth: alienation increases aggression following peer rejection.

    PubMed

    Reijntjes, Albert; Thomaes, Sander; Bushman, Brad J; Boelen, Paul A; de Castro, Bram Orobio; Telch, Michael J

    2010-10-01

    Although there are good theoretical reasons to believe that youth who are high in alienation (i.e., estranged from society, significant others, and themselves) are prone to behave aggressively, empirical evidence is lacking. The present experiment tested whether alienation moderates the effects of acute peer rejection on aggression in youth. Participants (N = 121; mean age = 11.5 years) completed a personal profile (e.g., "How do you describe yourself?") that was allegedly evaluated online by a panel of peer judges. After randomly receiving negative or positive feedback from peer judges, participants were given the opportunity to aggress against them (i.e., by reducing their monetary reward and by posting negative comments about them online). As predicted, alienation increased participants' aggression against peers who had rejected them, but not against peers who had praised them, even after controlling for peer-nominated chronic rejection and peer-nominated aggression. Thus, alienated youth are more aggressive than others when they experience acute peer rejection.

  17. Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients.

    PubMed

    Moreso, F; Serón, D; Gil-Vernet, S; Riera, L; Fulladosa, X; Ramos, R; Alsina, J; Grinyó, J M

    1999-04-01

    Transplant recipients of kidneys harvested from old donors have a high incidence of delayed graft function (DGF) and a poor graft outcome. This result is partly explained by the increased incidence of acute rejection in patients suffering from DGF. However, the long-term impact of donor age and DGF in rejection free renal transplants is not well established. The aim of the present work is to evaluate the impact of donor age and DGF on long-term outcome in renal transplants with or without acute rejection. We review all cadaveric kidney transplants performed in our centre between April 1984 and December 1995 treated with a cyclosporin-based immunosuppression. Five hundred and ninety-five patients were included. The overall incidence of DGF was 29.1%, and this event was associated with an increased donor age and cold ischaemia time. Univariate and multivariate analysis showed that graft loss was associated with acute rejection (relative risk (RR) 2.24, 95% confidence interval (CI) 1.62-3.01); DGF (RR 1.83, 95% CI 1.32-2.54); donors >50 years (RR 1.65, 95% CI 1.13-2.38); and retransplantation (RR 1.52, 95% CI 1.01-2.31). In rejection-free patients there were two independent predictors of graft failure: donor >50 years (RR 2.40, 95% CI 1.45-4.01); and DGF (RR 2.42, 95% CI 1.53-3.84). Regardless of the presence of acute rejection, delayed graft function amplifies the detrimental effect of advanced donor age on long-term graft outcome.

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

    PubMed Central

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

    2014-01-01

    In this study, we show that aly/aly mice, which are devoid of lymph nodes and Peyer’s patches, rejected acutely fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts were also rejected acutely by splenectomized aly/aly mice (aly/aly-spl−) 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 in aly/aly-spl− mice. Actually, aly/aly-spl− mice having spontaneously accepted a heart allotransplant 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

  19. Augmenter of liver regeneration attenuates acute rejection after rat liver transplantation.

    PubMed

    Chen, Yong; Liang, Shaoyong; Long, Feiwu; Li, Jinzheng; Gong, Jianping

    2016-07-01

    The role of augmenter of liver regeneration (ALR) on liver transplantation immune regulation remains unknown. Male Lewis and Brown-Norway (BN) rats were assigned to allograft group (Lewis-to-BN liver transplantation), isograft group (BN-to-BN), and ALR group (Lewis-to-BN, ALR, 100 μg/kg/d, intramuscular injection postoperatively). Rats were sacrificed at indicated times for assessment of cytokines production, T-cell (TC) activation and apoptosis. Kupffer cells (KCs) and TCs were isolated from grafts to assess cytokine expression. Effect of ALR and KCs on TCs was monitored by co-culture of (3)H-thymidine TCs. (1) Treatment with ALR significantly decreased interleukin-2 and interferon-γ expression, promoted TC apoptosis, and prolonged the survival of allografts; (2) KCs in ALR group and isograft group that had significantly increased interleukin-10 and decreased tumor necrosis factor-α expression were able to inhibit TC proliferation and induce their apoptosis relative to KCs in the allograft group; (3) ALR and KCs directly inhibited TC proliferation and activation and induced TC apoptosis. ALR could inhibit TC proliferation and function both in vivo and in vitro and attenuate acute rejection after liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Rejection sensitivity prospectively predicts increased rumination.

    PubMed

    Pearson, Katherine A; Watkins, Edward R; Mullan, Eugene G

    2011-10-01

    Converging research findings indicate that rumination is correlated with a specific maladaptive interpersonal style encapsulating submissive (overly-accommodating, non-assertive and self-sacrificing) behaviours, and an attachment orientation characterised by rejection sensitivity. This study examined the prospective longitudinal relationship between rumination, the submissive interpersonal style, and rejection sensitivity by comparing two alternative hypotheses: (a) the submissive interpersonal style and rejection sensitivity prospectively predict increased rumination; (b) rumination prospectively predicts the submissive interpersonal style and rejection sensitivity. Currently depressed (n = 22), previously depressed (n = 42) and never depressed (n = 28) individuals completed self-report measures assessing depressive rumination and key psychosocial measures of interpersonal style and behaviours, at baseline and again six months later. Baseline rejection sensitivity prospectively predicted increased rumination six months later, after statistically controlling for baseline rumination, gender and depression. Baseline rumination did not predict the submissive interpersonal style or rejection sensitivity. The results provide a first step towards delineating a potential casual relationship between rejection sensitivity and rumination, and suggest the potential value of clinical assessment and intervention for both rejection sensitivity and rumination in individuals who present with either difficulty. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Early subclinical rejection as a risk factor for late chronic humoral rejection.

    PubMed

    Moreso, Francesc; Carrera, Marta; Goma, Montse; Hueso, Miguel; Sellares, Joana; Martorell, Jaume; Grinyó, Josep M; Serón, Daniel

    2012-01-15

    Subclinical rejection and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsies are associated with outcome. We study the relationship between histologic lesions in early protocol biopsies and histologic diagnoses in late biopsies for cause. Renal transplants with a protocol biopsy performed within the first 6 months posttransplant between 1988 and 2006 were reviewed. Biopsies were evaluated according to Banff criteria, and C4d staining was available in biopsies for cause. Of the 517 renal transplants with a protocol biopsy, 109 had a subsequent biopsy for cause which showed the following histological diagnoses: chronic humoral rejection (CHR) (n=44), IF/TA (n=42), recurrence of the primary disease (n=11), de novo glomerulonephritis (n=7), T-cell-mediated rejection (n=4), and polyoma virus nephropathy (n=1). The proportion of retransplants (15.9% vs. 2.3%, P=0.058) and the prevalence of subclinical rejection were higher in patients with CHR than in patients with IF/TA (52.3% vs. 28.6%, P=0.0253). Demographic donor and recipient characteristics and clinical data at the time of protocol biopsy were not different between groups. Logistic regression analysis showed that subclinical rejection (relative risk, 2.52; 95% confidence interval, 1.1-6.3; P=0.047) but not retransplantation (relative risk, 6.7; 95% confidence interval, 0.8-58.8; P=0.085) was associated with CHR. Subclinical rejection in early protocol biopsies is associated with late appearance of CHR.

  2. N-Acetyl Cysteine does not prevent liver toxicity from chronic low dose plus sub-acute high dose paracetamol exposure in young or old mice

    PubMed Central

    Kane, Alice-Elizabeth; Huizer-Pajkos, Aniko; Mach, John; McKenzie, Catriona; Mitchell, Sarah-Jayne; de Cabo, Rafael; Jones, Brett; Cogger, Victoria; Le Couteur, David G; Hilmer, Sarah-Nicole

    2016-01-01

    Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute over-exposures. The risk of hepatotoxicity from non-acute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for non-acute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and sub-acute paracetamol over-exposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33g/kg food) or control diet for 6 weeks. Mice were then dosed orally 8 times over 3 days with additional paracetamol (250mg/kg) or saline, followed by either one or two doses of oral NAC (1200mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Sub-acute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from sub-acute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for sub-acute paracetamol toxicity. PMID:26821200

  3. Histopathology of spleen allograft rejection in miniature swine

    PubMed Central

    Dor, Frank J M F; Gollackner, Bernd; Kuwaki, Kenji; Ko, Dicken S C; Cooper, David K C; Houser, Stuart L

    2005-01-01

    Spleen transplantation (SpTx) has established donor-specific tolerance in rodents, but not in large animals or humans. We report the histopathology of rejection in an established model of SpTx in major histocompatibility complex (MHC)-defined miniature swine. Of the 17 SpTx, rejection was observed in two grafts transplanted into untreated, MHC-matched, minor antigen-disparate recipients (group 1, n = 4), but not in the two that received a 12-day course of cyclosporin A (CyA). Rejection also occurred in five grafts transplanted into fully MHC-disparate recipients (group 2, n = 12), one of which was untreated and four of which received some form of immunosuppressive therapy. One recipient of an MHC class-I-mismatched spleen treated with 12 days of CyA did not show rejection. Following biopsy and/or necropsy, fixed allograft tissue sections were treated with multiple stains, immunohistochemical markers and TUNEL assay. Common features of rejection occurred in grafts from both groups, but with varying time courses. Necrosis developed as early as day 8 in group 2 and day 27 in group 1, ranging from focal fibrinoid necrosis of arteriolar walls and sinusoids to diffuse liquefactive necrosis, usually associated with haemorrhage. Other features of rejection included white pulp expansion by atypical cells and decreased staining of basement membranes and reticular fibres. A doubling of the baseline TUNEL index preceded histologically identifiable rejection. This study establishes histologic guidelines for diagnosing and, perhaps, in future studies, predicting acute rejection of splenic allografts transplanted across known histocompatibility barriers in a large-animal model. PMID:15676033

  4. Pre-transplant soluble CD30 level as a predictor of not only acute rejection and graft loss but pneumonia in renal transplant recipients.

    PubMed

    Wang, Dong; Wu, Wei-Zhen; Chen, Jin-Hua; Yang, Shun-Liang; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

    2010-02-01

    Pre-transplant sera of 586 renal graft recipients were tested to investigate whether soluble CD30 (sCD30) is a useful predictor of some severe clinical episodes post-transplant. Correlation analysis showed sCD30 level was significantly correlated with acute rejection (AR) (r=0.242, P<0.001), graft loss (r=0.162, P<0.001), and pneumonia (r=-0.147, P<0.001). Higher sCD30 levels were observed in patients with AR than the others (180.0+/-89.1 vs. 135.3+/-72.7U/ml, P<0.001). And patients with pneumonia had significantly lower pre-transplant sCD30 level than the others (123.2+/-75.5 vs. 150.7+/-79.6U/ml, P=0.003). Based on statistical results, 120 and 240U/ml were selected as the optimal couple of cut-off value to divide patients into three groups: Group High (H), Group Intermedial (I) and Group Low (L). The lowest AR rate of 17.4% was observed in Group L (P<0.001). Significant difference of AR rate was also observed between Group I (29.2%) and H (42.9%) (P<0.001). There were much more patients suffering pneumonia in Group L (P=0.001). Significantly lower 5-year patient survival rate (79.4%) was observed in Group H (P=0.016). These data showed that elevated pre-transplant sCD30 level of renal allograft recipients may reflect an immune state detrimental for renal allograft survival. But sCD30 level lower than <120U/ml may be associated with a high risk of pneumonia. Pre-transplant sCD30 level is an independent predictor of acute rejection, lung infection, even graft survival. Suitable immunosuppression protocol should be selected according to pre-transplant sCD30 level in an attempt to promote patient and graft survival. Copyright 2010 Elsevier B.V. All rights reserved.

  5. Pending laboratory tests and the hospital discharge summary in patients discharged to sub-acute care.

    PubMed

    Walz, Stacy E; Smith, Maureen; Cox, Elizabeth; Sattin, Justin; Kind, Amy J H

    2011-04-01

    Previous studies have noted a high (41%) prevalence and poor discharge summary communication of pending laboratory (lab) tests at the time of hospital discharge for general medical patients. However, the prevalence and communication of pending labs within a high-risk population, specifically those patients discharged to sub-acute care (i.e., skilled nursing, rehabilitation, long-term care), remains unknown. To determine the prevalence and nature of lab tests pending at hospital discharge and their inclusion within hospital discharge summaries, for common sub-acute care populations. Retrospective cohort study. Stroke, hip fracture, and cancer patients discharged from a single large academic medical center to sub-acute care, 2003-2005 (N = 564) Pending lab tests were abstracted from the laboratory information system (LIS) and from each patient's discharge summary, then grouped into 14 categories and compared. Microbiology tests were sub-divided by culture type and number of days pending prior to discharge. Of sub-acute care patients, 32% (181/564) were discharged with pending lab tests per the LIS; however, only 11% (20/181) of discharge summaries documented these. Patients most often left the hospital with pending microbiology tests (83% [150/181]), particularly blood and urine cultures, and reference lab tests (17% [30/181]). However, 82% (61/74) of patients' pending urine cultures did not have 24-hour preliminary results, and 19% (13/70) of patients' pending blood cultures did not have 48-hour preliminary results available at the time of hospital discharge. Approximately one-third of the sub-acute care patients in this study had labs pending at discharge, but few were documented within hospital discharge summaries. Even after considering the availability of preliminary microbiology results, these omissions remain common. Future studies should focus on improving the communication of pending lab tests at discharge and evaluating the impact that this improved

  6. Combined use of rapamycin and leflunomide in prevention of acute cardiac allografts rejection in rats.

    PubMed

    Sun, Yan; Chen, Xi; Zhao, Jiabin; Zou, Xiaoming; Li, Gang; Li, Xiaolin; Shen, Bin; Sun, Shibo

    2012-08-01

    This study aimed to evaluate the role of combined use of rapamycin and leflunomide(Lef) on the prevention of acute allograft rejection in rats. After cardiac transplantations, rats were randomly divided into untreated group, rapamycin group, Lef group and rapamycin+Lef group. The drugs were given by gavage from day 0 to day 9 after transplantations. Graft survival time was observed. Some grafts were harvested for histopathological investigation on day 10 after transplantations. The levels of CD(4)(+) and CD(8)(+) T lymphocytes and the concentrations of interleukin 2(IL-2) and interferon (IFN)γ in peripheral blood were examined on day 10 after transplantations. At the same time, the body weight, the hepatic function, renal function and the haemoglobin of the recipients were also examined. The graft survival time of untreated group was 7.14 ± 1.07 days. Rapamycin group was 11.14 ± 1.35 days. Lef group was 11.29 ± 1.80 days. While in rapamycin+Lef group, the graft survival time was prolonged to 13.86 ± 1.57 days(P<0.05). Histological changes of the allografts in rapamycin+Lef group were much milder than either of the two single drug groups. The absolute number and the percentage of CD(4)(+) T lymphocytes in peripheral blood in rapamycin+Lef group were lower than those of rapamycin or Lef group on day 10 after transplantations(P<0.05), while the percentage of CD(8)(+) T lymphocytes in rapamycin+Lef group was higher than that of rapamycin or Lef group(P<0.05). The absolute number of CD(8)(+) T lymphocytes was not significantly different among rapamycin group, Lef group and rapamycin+Lef group. The levels of IL-2 and IFN-γ in rapamycin+Lef group were significantly lower than that of rapamycin group or Lef group(P<0.05). The body weight, the hepatic function, renal function and the haemoglobin were not significantly different among rapamycin group, Lef group and rapamycin+Lef group (P>0.05). Combined use of rapamycin and Lef had better effect on the prevention of

  7. Therapeutic potency of bee pollen against biochemical autistic features induced through acute and sub-acute neurotoxicity of orally administered propionic acid.

    PubMed

    Al-Salem, Huda S; Bhat, Ramesa Shafi; Al-Ayadhi, Laila; El-Ansary, Afaf

    2016-04-23

    It is now well documented that postnatal exposure to certain chemicals has been reported to increase the risk of autism spectrum disorder. Propionic acid (PA), as a metabolic product of gut microbiotaandas a commonly used food additive, has been reported to mediate the effects of autism. Results from animal studies may help to identify environmental neurotoxic agents and drugs that can ameliorate neurotoxicity and may thereby aid in the treatment of autism. The present study investigated the ameliorative effects of natural bee pollen against acute and sub-acute brain intoxication induced by (PA) in rats. Twenty-four young male Western Albino ratswere enrolled in the present study. They were classified into four equal groups, eachwith6 rats. The control group received only phosphate buffered saline; the oral buffered PA-treated groups (II and III) received a neurotoxic dose of 750 mg/kg body weight divided in 3 dose of 250 mg/kg body weight/day serving asthe acute group and 750 mg/kg body weight divided in 10 equal dose of 75 mg/kg body weight/day as the sub-acute group. The fourth group received 50 mg bee pollen for 30 days after PA-acute intoxication. The obtained data showed that the PA-treated groups demonstrated multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), dopamine and nor-adrenaline, together withan increase in IFN-γ and caspase 3. Bee pollen was effective in ameliorating the neurotoxic effect of PA. All measured parameters demonstrated minimal alteration in comparison with thecontrol animal than did those of acute and sub-acute PA-treated animals. In conclusion, bee pollen demonstrates anti-inflammatory and anti-apoptotic effects while ameliorating the impaired neurochemistry of PA-intoxicated rats.

  8. [Sub-acute encephalopathy that responds to steroids without any evidence of autoimmune thyroid disease: a case of non-vasculitic autoimmune meningoencephalitis].

    PubMed

    López-Ariztegui, N; Lobato-Casado, P; Muñoz-Escudero, F; Polo-Martín, M; Montes-Gonzalo, M C; Alvarez-Tejerina, A

    To report a case of sub-acute encephalopathy with all the extension study negative and with response to steroid therapy. The study involves a 22-year-old female with no relevant past history who presented symptoms of sub-acute encephalopathy consisting in behavioural disorders, generalised seizures and bradypsychia, which gradually progressed to a state of low-level consciousness. While she was in hospital all kinds of diagnostic tests were conducted, the results of which were either normal or negative; the electroencephalogram was repeatedly abnormal and detection of protein 14-3-3 in cerebrospinal fluid was positive. Empirical corticoid therapy was begun with clinical and electrophysiological improvements and the patient recovered completely without any sequelae. With no evidence of autoimmune thyroid disease, although non-specific autoimmunity was present, the patient was diagnosed as having non-vasculitic autoimmune meningoencephalitis.

  9. Evaluation of acute and sub-acute toxicity of Pinus eldarica bark extract in Wistar rats

    PubMed Central

    Ghadirkhomi, Akram; Safaeian, Leila; Zolfaghari, Behzad; Agha Ghazvini, Mohammad Reza; Rezaei, Parisa

    2016-01-01

    Objective: Pinus eldarica (P. eldarica) is one of the most common pines in Iran which has various bioactive constituents and different uses in traditional medicine. Since there is no documented evidence for P. eldarica safety, the acute and sub-acute oral toxicities of hydroalcoholic extract of P. eldarica bark were investigated in male and female Wistar rats in this study. Materials and Methods: In the acute study, a single dose of extract (2000 mg/kg) was orally administered and animals were monitored for 7 days. In the sub-acute study, repeated doses (125, 250 and 500 mg/kg/day) of the extract were administered for 28 days and biochemical, hematological and histopathological parameters were evaluated. Results: Our results showed no sign of toxicity and no mortality after single or repeated administration of P. eldarica. The median lethal dose (LD50) of P. eldarica was determined to be higher than 2000 mg/kg. The mean body weight and most of the biochemical and hematological parameters showed normal levels. There were only significant decreases in serum triglyceride levels at the doses of 250 and 500 mg/kg of the extract in male rats (p<0.05 and p<0.01, respectively) and in monocyte counts at the highest dose of the extract in both male and female rats (p<0.05). Mild inflammation was also found in histological examination of kidney and liver tissues at the highest dose of extract. Conclusion: Oral administration of the hydroalcoholic extract of P. eldarica bark may be considered as relatively non-toxic particularly at the doses of 125 and 250 mg/kg. PMID:27761426

  10. Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection

    PubMed Central

    Lerret, Nadine M.; Li, Ting; Wang, Jiao-Jing; Kang, Hee-Kap; Wang, Sheng; Wang, Xueqiong; Jie, Chunfa; Kanwar, Yashpal S.; Abecassis, Michael M.

    2015-01-01

    The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88−/− recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b−Gr-1+ cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88−/− recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88−/− recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88−/− T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection. PMID:25788530

  11. Interstitial pneumonitis and the risk of chronic allograft rejection in lung transplant recipients.

    PubMed

    Mihalek, Andrew D; Rosas, Ivan O; Padera, Robert F; Fuhlbrigge, Anne L; Hunninghake, Gary M; DeMeo, Dawn L; Camp, Phillip C; Goldberg, Hilary J

    2013-05-01

    The presence of interstitial pneumonitis (IP) on surveillance lung biopsy specimens in lung transplant recipients is poorly described, and its impact on posttransplant outcomes is not established. The following study assessed the association of posttransplant IP with the development of bronchiolitis obliterans syndrome (BOS). We examined all recipients of primary cadaveric lung transplants at our institution between January 1, 2000, and December 31, 2007 (N = 145). Patients had bronchoscopies with BAL, and transbronchial biopsies performed for surveillance during posttransplant months 1, 3, 6, and 12 as well as when clinically indicated. Patients were given a diagnosis of IP if, in the absence of active infection and organizing pneumonia, they showed evidence of interstitial inflammation and fibrosis on two or more biopsy specimens. IP was a significant predictor of BOS (OR, 7.84; 95% CI, 2.84-21.67; P < .0001) and was significantly associated with time to development of BOS (hazard ratio, 3.8; 95% CI, 1.93-7.39; P = .0001) within the first 6 years posttransplant. The presence of IP did not correlate with a significantly higher risk of mortality or time to death. There was no association between the presence of IP and the development of or time to acute rejection. The presence of IP on lung transplant biopsy specimens suggests an increased risk for BOS, which is independent of the presence of acute cellular rejection.

  12. Subclinical rejection in renal transplants is associated with low serum mannose-binding lectin levels.

    PubMed

    Ibernon, Meritxell; Moreso, Francesc; Serón, Daniel

    2011-08-01

    Surveillance biopsies have contributed to the understanding of the natural history of renal allograft lesions. Subclinical rejection, defined as the presence of histological lesions, indistinguishable from acute rejection in stable grafts, is associated with progression of interstitial fibrosis and tubular atrophy. The prevalence of subclinical rejection has decreased as more powerful immunosuppressive treatments have been introduced, suggesting that subclinical rejection represents the degree of control of the alloimmune response. However, non-immune factors such as donor age are also associated with the prevalence of subclinical rejection, suggesting that kidneys from older donors are more susceptible to insult and have a reduced capacity for tissue regeneration. Innate immunity has a crucial role in the modulation of the inflammatory response during infection and tissue damage. Mannose-binding lectin (MBL) is an innate immune protein, the polymorphisms of which are associated with infection, low-grade inflammation, diabetes, and cardiovascular disease. However, the relationship between MBL and disease is complex. For example, low MBL level is associated with higher risk for diabetes, whereas in patients with diabetes, high MBL level is associated with more severe renal damage. In renal transplant patients, low MBL levels are associated with an increased prevalence of infection and diabetes, whereas high MBL levels are associated with shortened graft survival. Although MBL is not clearly associated with prevalence of acute rejection, surveillance biopsy studies have shown that low MBL levels are associated with subclinical rejection in kidney and the heart, suggesting that MBL modulates the injury-repair process of the allograft.

  13. Subclinical rejection in renal transplants is associated with low serum mannose-binding lectin levels

    PubMed Central

    Ibernon, Meritxell; Moreso, Francesc; Serón, Daniel

    2011-01-01

    Surveillance biopsies have contributed to the understanding of the natural history of renal allograft lesions. Subclinical rejection, defined as the presence of histological lesions, indistinguishable from acute rejection in stable grafts, is associated with progression of interstitial fibrosis and tubular atrophy. The prevalence of subclinical rejection has decreased as more powerful immunosuppressive treatments have been introduced, suggesting that subclinical rejection represents the degree of control of the alloimmune response. However, non-immune factors such as donor age are also associated with the prevalence of subclinical rejection, suggesting that kidneys from older donors are more susceptible to insult and have a reduced capacity for tissue regeneration. Innate immunity has a crucial role in the modulation of the inflammatory response during infection and tissue damage. Mannose-binding lectin (MBL) is an innate immune protein, the polymorphisms of which are associated with infection, low-grade inflammation, diabetes, and cardiovascular disease. However, the relationship between MBL and disease is complex. For example, low MBL level is associated with higher risk for diabetes, whereas in patients with diabetes, high MBL level is associated with more severe renal damage. In renal transplant patients, low MBL levels are associated with an increased prevalence of infection and diabetes, whereas high MBL levels are associated with shortened graft survival. Although MBL is not clearly associated with prevalence of acute rejection, surveillance biopsy studies have shown that low MBL levels are associated with subclinical rejection in kidney and the heart, suggesting that MBL modulates the injury–repair process of the allograft. PMID:25018901

  14. Donor-specific HLA alloantibodies: Impact on cardiac allograft vasculopathy, rejection, and survival after pediatric heart transplantation.

    PubMed

    Tran, Andrew; Fixler, David; Huang, Rong; Meza, Tiffany; Lacelle, Chantale; Das, Bibhuti B

    2016-01-01

    There is increasing evidence that donor-specific anti-HLA antibodies (DSA) are associated with poor outcomes after cardiac transplantation in adults, but data are limited in children. The objective of this study was to examine the development and consequences of de novo DSA in pediatric recipients of heart transplants. We analyzed 105 pediatric patients who received heart transplants at our center from January 2002 to December 2012. All patients had negative T-cell and B-cell post-transplant crossmatches. Patients underwent HLA antibody screening at 1, 2, 3, 6, and 12 months post-transplant and annually thereafter unless there was suspicion for rejection. HLA class I and II antibodies were identified using Luminex assay. Coronary angiography was performed at 1 year and annually thereafter. Acute cellular rejection, antibody-mediated rejection, and treated clinical rejections were included together as rejection events. Of 105 patients, 45 (43%) developed de novo DSA. DSA-positive patients had significantly higher rates of coronary artery vasculopathy (CAV) compared with DSA-negative patients (36% vs 13%). CAV-free survival at 1 year and 5 years post-transplant for DSA-negative patients was 90% and 25%, respectively, compared with 70% and 0%, respectively, for DSA-positive patients (p < 0.01). DSA-positive patients had 2.5 times more rejection events per year than DSA-negative patients. The 5-year graft survival rate was 72.4% for DSA-negative patients and 21% for DSA-positive patients (p < 0.001). De novo DSA has a strong negative impact on CAV, rejection, and graft survival in pediatric recipients of heart transplants. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  15. PRINS Long Noncoding RNA Involved in IP-10-Mediated Allograft Rejection in Rat Kidney Transplant.

    PubMed

    Zou, X-F; Song, B; Duan, J-H; Hu, Z-D; Cui, Z-L; Yang, T

    2018-06-01

    Previously, high levels of CXCR3+ T-cell recruitment was demonstrated in the prolonged ischemia-accelerated acute allograft rejection in rat kidney transplant. In the present study, the effect of chemokine IP-10 was investigated and the expression of chemokine-related PRINS (Psoriasis susceptibility-related RNA gene induced by stress) lncRNA determined in the allografts subjected to ischemia. F344-to-Lewis rat kidney transplantation was performed, and renal grafts were stored for 2 hours or 16 hours. Samples were removed at 24 hours and 7 days after operation. Cellular infiltration was determined with the use of immunohistochemistry, and messenger RNA expression was assessed with the use of real-time polymerase chain reaction. The 16-hour-ischemia kidney displayed acute tubule damage and up-regulation of PRINS lncRNA expression. On day 7, IP-10 expression and CD3-positive T cells were increased in allografts compared with control samples, which were inhibited by the IP-10 antibody treatment accompanied by reduced serum creatinine. These observations provide evidence for IP-10 in a regulatory role in cold ischemia-elicited acute allograft rejection and in PRINS lncRNA expression. Our data enhance the understanding of the mechanism underlying between prolonged ischemia and acute rejection. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Clinical characteristics of acute encephalopathy with acute brain swelling: A peculiar type of acute encephalopathy.

    PubMed

    Nukui, Megumi; Kawawaki, Hisashi; Inoue, Takeshi; Kuki, Ichiro; Okazaki, Shin; Amo, Kiyoko; Togawa, Masao; Ishikawa, Junichi; Rinka, Hiroshi; Shiomi, Masashi

    2018-06-07

    Acute encephalopathy has been observed with acute brain swelling (ABS) that is characterized by rapid progression to whole-brain swelling. The objective of this study was to describe the clinical characteristics of ABS. We encountered four patients with ABS and retrospectively investigated their clinical data with a medical chart review. Three patients had seizure clustering or status epilepticus in the clinical course. Signs of elevated intracranial pressure (ICP) appeared 3-9 h after the first convulsive attack in three patients. In all patients, signs of brainstem involvement appeared 1-8 h after signs of elevated ICP. Mild hyponatremia that progressed after signs of elevated ICP appeared was noted in three patients. Brain CT revealed mild brain swelling in the initial phase, which rapidly progressed to whole-brain swelling. No focal abnormalities were detected on brain MRI in one patient. Continuous electroencephalography was initially normal, but in two patients, high-amplitude slow waves appeared with rapid changes before signs of brainstem involvement. Although recovery was achieved without sequelae in two patients, outcome was fatal for the other two. The pathogenesis of ABS has yet to be clarified, but clinical features in our patients are not consistent with any established subtypes of acute encephalopathy. Therefore, we believe that ABS should be recognized as a new type of acute encephalopathy. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  17. Electrically evoked compound action potentials artefact rejection by independent component analysis: procedure automation.

    PubMed

    Akhoun, Idrick; McKay, Colette; El-Deredy, Wael

    2015-01-15

    Independent-components-analysis (ICA) successfully separated electrically-evoked compound action potentials (ECAPs) from the stimulation artefact and noise (ECAP-ICA, Akhoun et al., 2013). This paper shows how to automate the ECAP-ICA artefact cancellation process. Raw-ECAPs without artefact rejection were consecutively recorded for each stimulation condition from at least 8 intra-cochlear electrodes. Firstly, amplifier-saturated recordings were discarded, and the data from different stimulus conditions (different current-levels) were concatenated temporally. The key aspect of the automation procedure was the sequential deductive source categorisation after ICA was applied with a restriction to 4 sources. The stereotypical aspect of the 4 sources enables their automatic classification as two artefact components, a noise and the sought ECAP based on theoretical and empirical considerations. The automatic procedure was tested using 8 cochlear implant (CI) users and one to four stimulus electrodes. The artefact and noise sources were successively identified and discarded, leaving the ECAP as the remaining source. The automated ECAP-ICA procedure successfully extracted the correct ECAPs compared to standard clinical forward masking paradigm in 22 out of 26 cases. ECAP-ICA does not require extracting the ECAP from a combination of distinct buffers as it is the case with regular methods. It is an alternative that does not have the possible bias of traditional artefact rejections such as alternate-polarity or forward-masking paradigms. The ECAP-ICA procedure bears clinical relevance, for example as the artefact rejection sub-module of automated ECAP-threshold detection techniques, which are common features of CI clinical fitting software. Copyright © 2014. Published by Elsevier B.V.

  18. HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients

    PubMed Central

    Chapman, Jeremy R.; Coates, Patrick T.; Lewis, Joshua R.; Russ, Graeme R.; Watson, Narelle; Holdsworth, Rhonda; Wong, Germaine

    2016-01-01

    Background and objectives The current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes. Design, setting, participants, & measurements Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models. Results Of the 788 recipients followed for a median of 2.8 years (resulting in 2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA-DQ mismatched kidneys, respectively. Compared with recipients who have received zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus 117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of 321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321 versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched kidneys, the adjusted hazard ratios for any and late rejections in recipients who had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively. HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for interaction =0.02), such that the association between HLA-DQ mismatches and AMR was statistically significant in those who have received one or two HLA-DR mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94). Conclusions HLA

  19. Relevance of MICA and other non-HLA antibodies in clinical transplantation.

    PubMed

    Sumitran-Holgersson, Suchitra

    2008-10-01

    The clinical importance of HLA-specific antibodies for organ allograft outcome is well established. In the past few years, there has been an increasing interest in non-HLA antigens as targets of injury in organ transplant recipients. This increased interest has been spurred by the fact that HLA-identical kidney transplants also undergo immunological rejections. Polymorphisms within non-HLA genes associated with evoking an immune response to alloantigens are currently being studied for their association with transplant outcome. Non-HLA antigens, such as the polymorphic MHC class I-related chain A (MICA), expressed on endothelial cells have been implicated in the pathogenesis of hyperacute, acute and chronic organ allograft rejections. Use of endothelial cells as targets may clarify the specificities of other clinically relevant non-HLA antibodies in graft rejections. This review summarizes past and current knowledge of the clinical importance and specificities of non-HLA antibodies, and mechanisms by which these antibodies may contribute to graft destruction in clinical transplantation. The aims of current research into the role of non-HLA antigens and their genetics in predicting outcome are to develop an improved insight into the basic science of transplantation and to develop a risk or prognostic index for use in the clinical setting. Non-HLA antibody responses are receiving increasing interest in acute and chronic rejection and specificity, affinity, and pathogenicity need to be investigated to estimate their contribution. Undoubtedly, this will continue to be an area of interest in terms of fully understanding the role of non-HLA antigens as targets of immune-mediated injury and the potential for clinical intervention.

  20. 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

  1. Phytochemical, sub-acute toxicity, and antibacterial evaluation of Cordia sebestena leaf extracts.

    PubMed

    Osho, Adeleke; Otuechere, Chiagoziem A; Adeosun, Charles B; Oluwagbemi, Tolu; Atolani, Olubunmi

    2016-03-01

    In Nigeria, Cordia sebestena (Boraginaceae), an understudied medicinal plant, is used in traditional medicine for the treatment of gastrointestinal disorders. In this study, we investigated the chemical composition, antibacterial potential, and sub-acute toxicity of C. sebestena leaves. Ethyl acetate extracts were analyzed using thin layer chromatography (TLC) and Fourier transform infrared (FTIR) spectrophotometry. The antibacterial potential of the extracts was tested against five standard bacteria, namely Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Clinical observations and blood parameters were used to evaluate the possible toxicity of C. sebestena. The TLC profile yielded 39 fractions, which were pooled to nine combined sub-fractions (A-I). The FTIR spectrum of sub-fraction H indicated the presence of aliphatic C-H stretching vibration at 2922 and 2850 cm-1, C=O stretch at 1734 and 1708 cm-1, and C=C stretch of aromatics and aliphatics at 1464 and (shoulder) 1618 cm-1, respectively. The fractions of the C. sebestena ethyl acetate leaf extract showed antibacterial potential across board, but fraction H had the highest antibacterial activity against B. cereus and S. aureus. The study also indicated the relatively low toxicity profile of the ethyl acetate leaf extract of C. sebestena in the liver of rats. The study showed that C. sebestena leaves have strong antibacterial potential and low toxicity, thereby underlying the scientific basis for their folkloric use in the management of microbial infections and its associated complications.

  2. Significant reduction of acute cardiac allograft rejection by selective janus kinase-1/3 inhibition using R507 and R545.

    PubMed

    Deuse, Tobias; Hua, Xiaoqin; Taylor, Vanessa; Stubbendorff, Mandy; Baluom, Muhammad; Chen, Yan; Park, Gary; Velden, Joachim; Streichert, Thomas; Reichenspurner, Hermann; Robbins, Robert C; Schrepfer, Sonja

    2012-10-15

    Selective inhibition of lymphocyte activation through abrogation of signal 3-cytokine transduction emerges as a new strategy for immunosuppression. This is the first report on the novel Janus kinase (JAK)1/3 inhibitors R507 and R545 for prevention of acute allograft rejection. Pharmacokinetic and in vitro enzyme inhibition assays were performed to characterize the drugs. Heterotopic Brown Norway-Lewis heart transplantations were performed to study acute cardiac allograft rejection, graft survival, suppression of cellular host responsiveness, and antibody production. Therapeutic and subtherapeutic doses of R507 (60 and 15 mg/kg 2 times per day) and R545 (20 and 5 mg/kg 2 times per day) were compared with those of tacrolimus (Tac; 4 and 1 mg/kg once per day). Plasma levels of R507 and R545 were sustained high for several hours. Cell-based enzyme assays showed selective inhibition of JAK1/3-dependent pathways with 20-fold or greater selectivity over JAK2 and Tyrosine kinase 2 kinases. After heart transplantation, both JAK1/3 inhibitors reduced early mononuclear graft infiltration, even significantly more potent than Tac. Intragraft interferon-γ release was significantly reduced by R507 and R545, and for interleukin-10 suppression, they were even significantly more potent than Tac. Both JAK1/3 inhibitors and Tac were similarly effective in reducing the host Th1 and Th2, but not Th17, responsiveness and similarly prevented donor-specific immunoglobulin M antibody production. Subtherapeutic and therapeutic R507 and R545 doses prolonged the mean graft survival and were similarly effective as 1 and 4 mg/kg Tac, respectively. In combination regimens, however, only R507 showed highly beneficial synergistic drug interactions with Tac. Both R507 and R545 are potent novel immunosuppressants with favorable pharmacokinetics and high JAK1/3 selectivity, but only R507 synergistically interacts with Tac.

  3. Delayed xenograft rejection.

    PubMed

    Hancock, W W

    1997-01-01

    The triumph of genetic engineering in overcoming hyperacute rejection (HAR) of a discordant organ xenograft is clear, but the promise of clinical application of xenotransplantation remains unfulfilled as further immunologic barriers are defined that lead to rejection of a vascularized xenograft within days of transplantation. This report describes the features of this second set of immunologic responses, collectively termed delayed xenograft rejection (DXR). DXR is a syndrome seen in xenograft recipients in which HAR has been avoided or suppressed by antibody depletion or blockade of complement activation. DXR may result, at least in part, from the persisting activation of those pathways first encountered during the HAR phase. Serial studies over several days after transplant show that, histologically, xenografts undergoing DXR demonstrate varying combinations of (1) progressive infiltration by activated macrophages and natural killer (NK) cells, (2) platelet aggregation and fibrin deposition throughout the microvasculature, and (3) endothelial activation. In various experimental models, DXR is T cell-independent and can occur in the absence of demonstrable xenoreactive antibodies. Hence DXR is probably best regarded as arising from the activation of innate host defense mechanisms coupled with failure of normal regulatory mechanisms due to manifold molecular incompatibilities. Although DXR-like features can be seen in concordant models, T cell involvement in the latter is probably requisite. Similarly, in a much muted form, aspects of a DXR-like process may contribute to numerous inflammatory processes, including allograft rejection. The importance of DXR in xenotransplantation is that its development appears resistant to all but the most dense and toxic forms of immunosuppression, which prolong xenograft survival at the expense of inducing host leukopenia, thrombocytopenia, and coagulopathies. It is likely that until the basis of DXR is more clearly understood

  4. Cost-effectiveness of a classification-based system for sub-acute and chronic low back pain.

    PubMed

    Apeldoorn, Adri T; Bosmans, Judith E; Ostelo, Raymond W; de Vet, Henrica C W; van Tulder, Maurits W

    2012-07-01

    Identifying relevant subgroups in patients with low back pain (LBP) is considered important to guide physical therapy practice and to improve outcomes. The aim of the present study was to assess the cost-effectiveness of a modified version of Delitto's classification-based treatment approach compared with usual physical therapy care in patients with sub-acute and chronic LBP with 1 year follow-up. All patients were classified using the modified version of Delitto's classification-based system and then randomly assigned to receive either classification-based treatment or usual physical therapy care. The main clinical outcomes measured were; global perceived effect, intensity of pain, functional disability and quality of life. Costs were measured from a societal perspective. Multiple imputations were used for missing data. Uncertainty surrounding cost differences and incremental cost-effectiveness ratios was estimated using bootstrapping. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated. In total, 156 patients were included. The outcome analyses showed a significantly better outcome on global perceived effect favoring the classification-based approach, and no differences between the groups on pain, disability and quality-adjusted life-years. Mean total societal costs for the classification-based group were 2,287, and for the usual physical therapy care group 2,020. The difference was 266 (95% CI -720 to 1,612) and not statistically significant. Cost-effectiveness analyses showed that the classification-based approach was not cost-effective in comparison with usual physical therapy care for any clinical outcome measure. The classification-based treatment approach as used in this study was not cost-effective in comparison with usual physical therapy care in a population of patients with sub-acute and chronic LBP.

  5. Baseline serum sitosterol level as predictor of adverse clinical events in acute coronary syndrome patients with dyslipidaemia: A sub-analysis of HIJ-PROPER.

    PubMed

    Yamaguchi, Junichi; Kawada-Watanabe, Erisa; Koyanagi, Ryo; Arashi, Hiroyuki; Sekiguchi, Haruki; Nakao, Koichi; Tobaru, Tetsuya; Tanaka, Hiroyuki; Oka, Toshiaki; Endo, Yasuhiro; Saito, Katsumi; Uchida, Tatsuro; Matsui, Kunihiko; Ogawa, Hiroshi; Hagiwara, Nobuhisa

    2018-05-05

    We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndrome patients with dyslipidaemia. This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 μg/mL; a median of baseline sitosterol level), and clinical outcomes were examined. The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy. Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Did You Reject Me for Someone Else? Rejections That Are Comparative Feel Worse.

    PubMed

    Deri, Sebastian; Zitek, Emily M

    2017-12-01

    Rejections differ. For those who are rejected, one important difference is whether they are rejected for someone else (comparative rejection) or no one at all (noncomparative rejection). We examined the effect of this distinction on emotional reactions to a rejection in four studies ( N = 608), one of which was fully preregistered. Our results show that comparative rejections feel worse than noncomparative rejections and that this may be because such rejections lead to an increased sense of exclusion and decreased belonging. Furthermore, we found evidence that, by default, people react to a rejection as though it were comparative-that is, in the absence of any information about whether they have been rejected for someone or no one, they react as negatively as if they were rejected for someone. Our discussion focuses on the implications of these findings, including why people often seek out information in the wake of a rejection.

  7. 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. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  8. ARFI-based tissue elasticity quantification and kidney graft dysfunction: first clinical experiences.

    PubMed

    Stock, K F; Klein, B S; Cong, M T Vo; Regenbogen, C; Kemmner, S; Büttner, M; Wagenpfeil, S; Matevossian, E; Renders, L; Heemann, U; Küchle, C

    2011-01-01

    changes in ARFI-quantification, resistive indices and the absolute change of kidney size on a percentage basis at these defined assessment times and compared the results with the final pathologic diagnosis. Histological results enumerated five cases of acute T-cell-mediated rejection, one case of calcineurin inhibitor toxicity and two cases of acute tubular necrosis. Calcineurin inhibitor toxicity and acute tubular necrosis were subsumed as "other pathologies". Mean ARFI-values showed an average increase of more than 15% percent in transplants with histologically proven acute rejection whereas no increase was seen in transplants with other pathologies. Mean RI-values showed no increase either in the diagnostic group of acute rejection, nor in the group with other pathologies. Kidney size showed a mean absolute increase of 0.5 centimetres in allografts with acute rejection, whereas a mean decrease of 0.17 centimetres was seen in the group with other pathologies. As shown before in other studies, RI values and kidney size are of doubtful utility in the evaluation of kidney allograft dysfunction. ARFI-based elasticity measurement shows promise as a complementary non-invasive parameter in follow-on diagnosis of renal allograft rejection.

  9. Paneth and intestinal stem cells preserve their functional integrity during worsening of acute cellular rejection in small bowel transplantation.

    PubMed

    Pucci Molineris, M; Gonzalez Polo, V; Perez, F; Ramisch, D; Rumbo, M; Gondolesi, G E; Meier, D

    2018-04-01

    Graft survival after small bowel transplantation remains impaired due to acute cellular rejection (ACR), the leading cause of graft loss. Although it was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, no results of Paneth and intestinal stem cells localized at the crypt bottom have been shown so far. Therefore, we wanted to elucidate integrity and functionality of the Paneth and stem cells during different degrees of ACR, and to assess whether these cells are the primary targets of the rejection process. We compared biopsies from ITx patients with no, mild, or moderate ACR by immunohistochemistry and quantitative PCR. Our results show that numbers of Paneth and stem cells remain constant in all study groups, whereas the transit-amplifying zone is the most impaired zone during ACR. We detected an unchanged level of antimicrobial peptides in Paneth cells and similar numbers of Ki-67 + IL-22R + stem cells revealing cell functionality in moderate ACR samples. We conclude that Paneth and stem cells are not primary target cells during ACR. IL-22R + Ki-67 + stem cells might be an interesting target cell population for protection and regeneration of the epithelial monolayer during/after a severe ACR in ITx patients. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. The relations between secrecy, rejection sensitivity and autonomy-connectedness.

    PubMed

    Wismeijer, Andreas A J; Van Assen, Marcel A L M; Bekker, Marrie H J

    2014-01-01

    The aim of this study was to examine the effects of two attachment-related variables on secrecy: rejection sensitivity and autonomy-connectedness. We hypothesized that rejection sensitivity is positively associated with secrecy, and autonomy-connectedness negatively with rejection sensitivity and secrecy. These hypotheses were generally corroborated in a sample of 303 university students. Moreover, we found that autonomy-connectedness at least partly explained the association between rejection sensitivity and secrecy. Self-awareness was negatively related to secrecy, suggesting that being aware of what one needs and thinks and being able to realize one's needs in social interactions reduce the tendency to keep secrets. In addition, interesting gender effects were found suggesting that men have a higher tendency to have secrets than women after controlling for the effects of autonomy-connectedness and rejection sensitivity. Our findings deepen the insight into possible reasons behind established associations between rejection sensitivity and secrecy, and may have clinical implications.

  11. Clinical Evidence of Acute Mesoamerican Nephropathy.

    PubMed

    Fischer, Rebecca S B; Mandayam, Sreedhar; Chavarria, Denis; Vangala, Chandan; Nolan, Melissa S; Garcia, Linda L; Palma, Lesbia; Garcia, Felix; García-Trabanino, Ramón; Murray, Kristy O

    2017-10-01

    Mesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua. Physicians at a local hospital identified suspect cases and documented clinical/laboratory data, demographics, and medical histories. Over a 1-year period, physicians identified 255 mostly young (median 29 years), male (89.5%) patients with elevated creatinine or reduced creatinine clearance. Mean serum creatinine (2.0 ± 0.6 mg/dL) revealed a 2-fold increase from baseline, and half had stage 2 or 3 acute kidney injury. Leukocyturia (98.4%), leukocytosis (81.4%), and neutrophilia (86.2%) predominated. Nausea (59.4%), back pain (57.9%), fever (54.6%), vomiting (50.4%), headache (47.3%), and muscle weakness (45.0%) were common. A typical case of acute MeN presented with elevated (or increased ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline) creatinine, no hypertension or diabetes, leukocyturia, and at least two of fever, nausea or vomiting, back pain, muscle weakness, headache, or leukocytosis and/or neutrophilia. Rapid progression (median 90 days) to CKD was recorded in 8.5% of patients. This evidence can serve as the basis of a sensitive and urgently needed case definition for disease surveillance of early-stage, acute MeN.

  12. Peer victimization and peer rejection during early childhood.

    PubMed

    Godleski, Stephanie A; Kamper, Kimberly E; Ostrov, Jamie M; Hart, Emily J; Blakely-McClure, Sarah J

    2015-01-01

    The development and course of the subtypes of peer victimization is a relatively understudied topic despite the association of victimization with important developmental and clinical outcomes. Moreover, understanding potential predictors, such as peer rejection and emotion regulation, in early childhood may be especially important to elucidate possible bidirectional pathways between relational and physical victimization and rejection. The current study (N = 97) was designed to explore several gaps and limitations in the peer victimization and peer rejection literature. In particular, the prospective associations between relational and physical victimization and peer rejection over the course of 3.5 months during early childhood (i.e., 3 to 5 years old) were investigated in an integrated model. The study consisted of 97 (42 girls) preschool children recruited from four early childhood schools in the northeast of the United States. Using observations, research assistant report, and teacher report, relational and physical aggression, relational and physical victimization, peer rejection, and emotion regulation were measured in a short-term longitudinal study. Path analyses were conducted to test the overall hypothesized model. Peer rejection was found to predict increases in relational victimization. In addition, emotion regulation was found to predict decreases in peer rejection and physical victimization. Implications for research and practice are discussed, including teaching coping strategies for peer rejection and emotional distress.

  13. Peer victimization and peer rejection during early childhood

    PubMed Central

    Godleski, Stephanie A.; Kamper, Kimberly E.; Ostrov, Jamie M.; Hart, Emily J.; Blakely-McClure, Sarah J.

    2014-01-01

    Objective The development and course of the subtypes of peer victimization is a relatively understudied topic despite the association of victimization with important developmental and clinical outcomes. Moreover, understanding potential predictors, such as peer rejection and emotion regulation, in early childhood may be especially important to elucidate possible bi-directional pathways between relational and physical victimization and rejection. The current study (N = 97) was designed to explore several gaps and limitations in the peer victimization and peer rejection literature. In particular, the prospective associations between relational and physical victimization and peer rejection over the course of 3.5 months during early childhood (i.e., 3- to 5- years-old) were investigated in an integrated model. Method The study consisted of 97 (42 girls) preschool children recruited from four early childhood schools in the northeast of the US. Using observations, research assistant report and teacher report, relational and physical aggression, relational and physical victimization, peer rejection, and emotion regulation were measured in a short-term longitudinal study. Path analyses were conducted to test the overall hypothesized model. Results Peer rejection was found to predict increases in relational victimization. In addition, emotion regulation was found to predict decreases in peer rejection and physical victimization. Conclusions Implications for research and practice are discussed, including teaching coping strategies for peer rejection and emotional distress. PMID:25133659

  14. Soluble CD30 for the prediction and detection of kidney transplant rejection.

    PubMed

    Arjona, Alvaro

    2009-09-01

    Although safer and more effective immunosuppressants as well as enhanced immunosuppressive protocols are continuously being developed in order to increase graft survival, they come at the steep price of drug-related complications and important side effects. In addition, the value of panel reactive antibodies determination, which at present is the single most used indicator of an increased risk of transplant rejection, is now being reevaluated. Therefore, effective tailoring of immunosuppressive therapy minimizing the above-mentioned pitfalls requires the existence of dependable biomarkers that adequately monitor rejection risk both before and after transplantation. Here we review the data yielded by studies assessing the usefulness of measuring soluble CD30 levels (sCD30) in kidney transplant rejection. These data collectively show that sCD30 serum content has a considerable predictive/diagnostic value for acute rejection of renal grafts, particularly when measured a few days after transplantation. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

  15. 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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. CT diagnosis of a clinically unsuspected acute appendicitis complicating infectious mononucleosis.

    PubMed

    Zissin, R; Brautbar, O; Shapiro-Feinberg, M

    2001-01-01

    Acute appendicitis is a rare complication of infectious mononucleosis (IM). We describe a patient with IM and splenic rupture with a computerized tomography (CT) diagnosis of acute appendicitis during the acute phase of the infectious disease. Diagnostic imaging features of acute appendicitis were found on an abdominal CT performed for the evaluation of postoperative fever. Histologic examination confirmed the CT diagnosis of the clinically unsuspected acute appendicitis. Our case is unique both for the rarity of this complication and the lack of clinical symptoms.

  17. Kidney transplantation: evaluation and clinical outcome of 237 recipients at low, medium, high, or strong immunological risk of rejection.

    PubMed

    Nascimento, E; Fabreti de Oliveira, R A; Maciel, M D; Pereira, A B; das Mercêz de Lucas, F; Salomão-Filho, A; Pereira, W A; Moreira, J B; Vilaça, S S; de Castro Gontijo, R; Lasmar, M F; Vianna, H R; Magalhâes, A; Calazans, C A C; Simão-Filho, C; Vilela, B

    2014-01-01

    Donor-specific antibodies (DSAs) play a fundamental role in kidney transplantation. The identification of DSAs is an essential rejection parameter. We evaluated a protocol in 237 patients receiving kidneys from living (LDs) and deceased donors (DDs). Recipients were classified as being at low (LR), medium (MR), high (HR), or strong (SR) risk of rejection based on Luminex panel reactive antibody (PRA)-single antigen beads (SABs). Grafts that survived for 1 year were evaluated. Of the 237 transplanted patients, 129 (54.43%) received a kidney from an LD and 108 (45.57%) from a DD. Of 95 LR recipients receiving kidneys from LDs, 2 patients lost the graft due to non-immunological causes. Of 34 MR recipients, 13 had rejection episodes, and 2 lost the graft by AMR and one by cellular rejection (CR). Of 108 recipients receiving a kidney from a DD, 59 (54.63%) were LR, 31 (28.70%) MR, 11 (10.19%) HR, and 7 (6.48%) SR. Twenty of all transplanted recipients lost their grafts; 4 were due to clinical causes, 4 by cellular rejection, and 12 by antibody-mediated rejection (AMR) with PRA-SAB mean fluorescent intensity of 530 to 12,591. One-year graft survival for LD transplanted LR and MR patients was 97.6% and 94.1%, respectively (P = .004). In DD recipients, the LR vs MR SD was P = .011, and for LR vs HR + SR it was P = .001. For MR vs HR+SR no SD was found (P = .323). Rejections were detected in 51 patients (21.52%). Graft failure occurred in 16 patients (6.75%). A total of 218 (91.98%) recipients maintained good kidney function after 1 year. This protocol based on fluxogram risk assessment of AMR provided fast and precise immunological evaluation of recipients and donors and stratification by immunological risk of AMR. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Medical emergency response in a sub-acute hospital: improving the model of care for deteriorating patients.

    PubMed

    Visser, Philip; Dwyer, Alison; Moran, Juli; Britton, Mary; Heland, Melodie; Ciavarella, Filomena; Schutte, Sandy; Jones, Daryl

    2014-05-01

    To assess the frequency, characteristics and outcomes of medical emergency response (MER) calls in a sub-acute hospital setting. The present study was a retrospective observational study in a sub-acute hospital providing aged care, palliative care, rehabilitation, veteran's mental health and elective surgical services. We assessed annual MER call numbers between 2005 and 2011 in the context of contemporaneous changes to hospital services. We also assessed MER calls over a 12-month period in detail using standardised case report forms and the scanned medical record. There were 2285 multiday admissions in the study period where 141 MER calls were triggered in 132 patients (61.7 calls per 1000 admissions). The median patient age was 83.0 years, and 55.3% of patients were men. Most calls occurred on weekdays and during the daytime, and were triggered by altered conscious state, low oxygen saturations and hypotension. Documentation of escalation of care before the MER call was not present in 99 of 141 (70.2%) calls. Following the call, in 70 of 141 (49.6%) cases, the patient was transferred to the acute campus, where 52 (74.2%) and 14 (20%) patients required ward and intensive care level treatment, respectively. Thirty-seven of 132 (28%) patients died. A palliative care physician adjudicated that most of these patients who died (24/37; 64.9%) were appropriate for a call, but that 19 (51.4%) should have received palliation at the time of the call. Compared with survivors, patients who died after the MER call were more likely originally admitted from supported accommodation. MER calls in our sub-acute hospital occurred in elderly patients and are associated with an in-hospital mortality of 28%. A small proportion of patients required intensive care level treatment. There is a need to improve processes involving escalation of care before MER call activation and to revise advance care directives. What is known about this topic? Rapid response team (RRT) activation has been

  19. Selected clinical aspects of acute intoxication with baclofen.

    PubMed

    Sein Anand, Jacek; Chodorowski, Zygmunt; Burda, Piotr

    2005-01-01

    Baclofen is a lipophilic analogue of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in central nervous system. The aim of the study was to evaluate some clinical aspects of acute intoxication with baclofen. Fifty two patients (37 females and 15 males) aged from 14 to 58 (mean 30.6 +/- 13.7) years were analyzed. Patients were admitted to the Clinic of Internal Diseases and Acute Poisonings Medical University of Gdańsk and the Centre of Acute Poisonings of Praski Hospital in Warszawa during the years 1996-2004 because of suicidal intoxication with baclofen. The doses of baclofen varied from 100 to 1500 (mean 444.8 +/- 317.8) mg. There were twenty eight patients (53.8%) in deep coma (III and IV grade of Matthew scale). Acute respiratory failure which required mechanical ventilation was observed in 18 cases (34.6%). Cardiac abnormalities included bradycardia (36.5%), hypertension (32.7%) and hypotension (3.8%). Toxic psychoses were observed in 6 cases (11.5%). The dosage of baclofen in patients with acute respiratory failure (ARF) was significantly higher than in patients without ARF. Treatment of patients with acute baclofen intoxication should take place in hospitals appropriately equipped which can provide artificial respiration.

  20. Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis.

    PubMed

    Chen, Yile; Tai, Qiang; Hong, Shaodong; Kong, Yuan; Shang, Yushu; Liang, Wenhua; Guo, Zhiyong; He, Xiaoshun

    2012-11-15

    The question of whether high pretransplantation soluble CD30 (sCD30) level can be a predictor of kidney transplant acute rejection (AR) is under debate. Herein, we performed a meta-analysis on the predictive efficacy of sCD30 for AR in renal transplantation. PubMed (1966-2012), EMBASE (1988-2012), and Web of Science (1986-2012) databases were searched for studies concerning the predictive efficacy of sCD30 for AR after kidney transplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of sCD30 were pooled. A summary receiver operating characteristic curve was used to represent the overall test performance. Twelve studies enrolling 2507 patients met the inclusion criteria. The pooled estimates for pretransplantation sCD30 in prediction of allograft rejection risk were poor, with a sensitivity of 0.70 (95% confidence interval (CI), 0.66-0.74), a specificity of 0.48 (95% CI, 0.46-0.50), a positive likelihood ratio of 1.35 (95% CI, 1.20-1.53), a negative likelihood ratio of 0.68 (95% CI, 0.55-0.84), and a diagnostic odds ratio of 2.07 (95% CI, 1.54-2.80). The area under curve of the summary receiver operating characteristic curve was 0.60, indicating poor overall accuracy of the serum sCD30 level in the prediction of patients at risk for AR. The results of the meta-analysis show that the accuracy of pretransplantation sCD30 for predicting posttransplantation AR was poor. Prospective studies are needed to clarify the usefulness of this test for identifying risks of AR in transplant recipients.

  1. The Clinical Spectrum of Renal Insufficiency During Acute Glomerulonephritis in the Adult

    PubMed Central

    Lemieux, Guy; Cuvelier, Amedee A.; Lefebvre, Rene

    1967-01-01

    Twenty-seven adults with acute poststreptococcal glomerulonephritis were divided into two groups according to the severity of reduction in renal function: (1) 14 patients with mild depression of renal function, and (2) 13 patients with more severe renal insufficiency. In the first group the outcome was favourable, with complete clinical recovery in 11 patients. Only two patients in the second group have recovered. Five have died of renal failure and in six the chronic stage has developed. The most notable histopathological lesion observed in this group of patients was severe proliferative glomerulonephritis with a large number of epithelial crescents. According to the mode of development and time of onset of renal failure, these 13 patients could be divided into three sub-groups: (1) early renal failure without oliguria (three patients), (2) early renal failure with severe oliguria or anuria (three patients) and (3) delayed renal failure (seven patients). Although there are exceptions, the development of renal insufficiency in an adult patient suffering from acute glomerulonephritis is usually associated with a guarded prognosis. ImagesFig. 2 PMID:6021561

  2. Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients.

    PubMed

    Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Feucht, Judith; Queudeville, Manon; Teltschik, Heiko-Manuel; Lang, Peter; Feuchtinger, Tobias; Handgretinger, Rupert; Müller, Ingo

    2016-01-01

    Diagnosis of adverse events following hematopoietic stem cell transplantation (HSCT) is mainly assigned to clinical symptoms or biopsies and thus rather unspecific and/or invasive. Studies indicate a distinct role of serum ferritin in HSCT and its correlation with adverse events such as graft-versus-host disease (GvHD), veno-occlusive disease (VOD), or infections. However, published data on the relevance of ferritin as a prognostic marker for post-transplant adverse events is rare, especially in pediatric patients. The present study analyzes ferritin plasma concentrations of 138 pediatric patients after HSCT between 2007 and 2010 including the control group (n = 21). Given the initial results regarding ferritin as a significant predictor for acute graft rejection after allogeneic HSCT in 9 of the 138 pediatric patients, serum ferritin of all pediatric patients (n = 27) who experienced graft rejection between 2007 and 2014 was analyzed. In addition, laboratory parameters including C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, and D-dimer as possible differentiation markers for graft rejection were determined. In 24 (88.9 %) of the 27 pediatric patients with graft rejection, a significant increase of ferritin levels was observed 1 to 7 days prior to (P < 0.0001) and at the time of graft rejection (P < 0.0001). Moreover, there was an increase of D-dimer, CRP, LDH, and fibrinogen 1-7 days before graft rejection. Ferritin increased significantly at time of VOD (P = 0.0067), at time of intestinal (P < 0.0001) and skin GvHD (P < 0.0001), and at time of sepsis (P = 0.0005) and bacteremia (P = 0.0029). Ferritin might serve as a readily available identification marker for differentiation and identification of adverse events after HSCT in combination with other laboratory markers.

  3. Computational Biomarker Pipeline from Discovery to Clinical Implementation: Plasma Proteomic Biomarkers for Cardiac Transplantation

    PubMed Central

    Cohen Freue, Gabriela V.; Meredith, Anna; Smith, Derek; Bergman, Axel; Sasaki, Mayu; Lam, Karen K. Y.; Hollander, Zsuzsanna; Opushneva, Nina; Takhar, Mandeep; Lin, David; Wilson-McManus, Janet; Balshaw, Robert; Keown, Paul A.; Borchers, Christoph H.; McManus, Bruce; Ng, Raymond T.; McMaster, W. Robert

    2013-01-01

    Recent technical advances in the field of quantitative proteomics have stimulated a large number of biomarker discovery studies of various diseases, providing avenues for new treatments and diagnostics. However, inherent challenges have limited the successful translation of candidate biomarkers into clinical use, thus highlighting the need for a robust analytical methodology to transition from biomarker discovery to clinical implementation. We have developed an end-to-end computational proteomic pipeline for biomarkers studies. At the discovery stage, the pipeline emphasizes different aspects of experimental design, appropriate statistical methodologies, and quality assessment of results. At the validation stage, the pipeline focuses on the migration of the results to a platform appropriate for external validation, and the development of a classifier score based on corroborated protein biomarkers. At the last stage towards clinical implementation, the main aims are to develop and validate an assay suitable for clinical deployment, and to calibrate the biomarker classifier using the developed assay. The proposed pipeline was applied to a biomarker study in cardiac transplantation aimed at developing a minimally invasive clinical test to monitor acute rejection. Starting with an untargeted screening of the human plasma proteome, five candidate biomarker proteins were identified. Rejection-regulated proteins reflect cellular and humoral immune responses, acute phase inflammatory pathways, and lipid metabolism biological processes. A multiplex multiple reaction monitoring mass-spectrometry (MRM-MS) assay was developed for the five candidate biomarkers and validated by enzyme-linked immune-sorbent (ELISA) and immunonephelometric assays (INA). A classifier score based on corroborated proteins demonstrated that the developed MRM-MS assay provides an appropriate methodology for an external validation, which is still in progress. Plasma proteomic biomarkers of acute cardiac

  4. Acute and sub-chronic toxicity of Cajanus cajan leaf extracts.

    PubMed

    Tang, Rong; Tian, Ru-Hua; Cai, Jia-Zhong; Wu, Jun-Hui; Shen, Xiao-Ling; Hu, Ying-Jie

    2017-12-01

    The leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse bioactivities, but little safety data are reported. This study examines the toxicological profiles of C. cajan leaf extracts. The leaves were extracted by water or 90% ethanol to obtain water or ethanol extract (WEC or EEC). EEC was suspended in water and successively fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker compounds of the extracts were monitored by high-performance liquid chromatography (HPLC). Kunming mice were administered with a single maximum acceptable oral dose (15.0 g/kg for WEC, EEC and BEC and 11.3 g/kg for DEC) to determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity investigation, Sprague-Dawley rats were orally given WEC or EEC at 1.5, 3.0 or 6.0 g/kg doses for four weeks and observed for two weeks after dosing to determine toxicological symptoms, histopathology, biochemistry and haematology. Flavonoids and stilbenes in the extracts were assayed. In acute toxicity test, no mortality and noted alterations in weight and behavioural abnormality were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic toxicity study, no mortality and significant variances in haematological and biochemical parameters or organ histopathology were observed, but increased kidney weight in 3.0 g/kg WEC- or 3.0 and 6.0 g/kg EEC-treated female rats, and reduced testes and epididymis weight in EEC-treated male rats were recorded. These changes returned to the level of control after recovery period. Acute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.

  5. C4d Deposition and Cellular Infiltrates as Markers of Acute Rejection in Rat Models of Orthotopic Lung Transplantation

    PubMed Central

    Murata, Kazunori; Iwata, Takekazu; Nakashima, Shinji; Fox-Talbot, Karen; Qian, Zhiping; Wilkes, David S.; Baldwin, William M.

    2008-01-01

    Background C4d is a useful marker of antibody-mediated rejection in cardiac and renal transplants, but clinical studies examining correlations between circulating alloantibodies, C4d deposition, and rejection in lung transplants have yielded conflicting results. Methods We studied circulating alloantibody levels and C4d deposition in two rat models of lung transplantation: Brown Norway (BN) to Wistar-Kyoto (WKY) and PVG.R8 to PVG.1U lung allografts. The availability of C6 deficient (C6−) and C6 sufficient (C6+) PVG 1U rats allowed evaluation of the effects of the terminal complement components on graft injury and C4d deposition. Results The lung allografts had histologic features resembling human posttransplant capillaritis, characterized by neutrophilic infiltration of alveoli, edema, and hemorrhage. Immunoperoxidase stains on cross sections of allografts showed intense, diffuse, C4d deposition in a continuous linear pattern on the vascular endothelium. C4d deposits were found in both BN to WKY and PVG R8 to 1U allografts, whereas no staining was detectable in WKY to WKY isografts or native lungs. Complement deposition was associated with vascular disruption in C6−, but not in C6+ recipients. The presence of circulating donor-specific alloantibodies was verified by flow cytometry. Cell-specific staining revealed perivascular accumulation of macrophages and T lymphocytes whereas neutrophils were sequestered in the intravascular and alveolar capillary compartments. Conclusions The deposition of C4d on vascular endothelium as well as the coincident presence of alloantibodies is consistent with previous findings in antibody-mediated rejection of renal and cardiac transplants. Furthermore, the histological features of our allografts support the concept that posttransplant capillaritis is a form of humoral rejection. PMID:18622289

  6. C4d-negative antibody-mediated rejection with high anti-angiotensin II type I receptor antibodies in absence of donor-specific antibodies.

    PubMed

    Fuss, Alexander; Hope, Christopher M; Deayton, Susan; Bennett, Greg Donald; Holdsworth, Rhonda; Carroll, Robert P; Coates, P Toby H

    2015-07-01

    Acute antibody-mediated rejection can occur in absence of circulating donor-specific antibodies. Agonistic antibodies targeting the anti-angiotensin II type 1 receptor (anti-AT1 R) are emerging as important non-human leucocyte antigen (HLA) antibodies. Elevated levels of anti-angiotensin II receptor antibodies were first observed in kidney transplant recipients with malignant hypertension and allograft rejection. They have now been studied in three separate kidney transplant populations and associate to frequency of rejection, severity of rejection and graft failure. We report 11 cases of biopsy-proven, Complement 4 fragment d (C4d)-negative, acute rejection occurring without circulating donor-specific anti-HLA antibodies. In eight cases, anti-angiotensin receptor antibodies were retrospectively examined. The remaining three subjects were identified from our centre's newly instituted routine anti-angiotensin receptor antibody screening. All subjects fulfilled Banff 2013 criteria for antibody-mediated rejection and all responded to anti-rejection therapy, which included plasma exchange and angiotensin receptor blocker therapy. These cases support the routine assessment of anti-AT1 R antibodies in kidney transplant recipients to identify subjects at risk. Further studies will need to determine optimal assessment protocol and the effectiveness of pre-emptive treatment with angiotensin receptor blockers. © 2015 Asian Pacific Society of Nephrology.

  7. Controlled study of neuroprosthetic functional electrical stimulation in sub-acute post-stroke rehabilitation.

    PubMed

    Ring, Haim; Rosenthal, Nechama

    2005-01-01

    Assess the effects of daily neuroprosthetic (NESS Handmaster) functional electrical stimulation in sub-acute stroke. Controlled study, patients clinically stratified to 2 groups; no active finger movement, and partial active finger movements, and then randomized to control and neuroprosthesis groups. Observer blinded evaluations at baseline and completion of the 6-week study. 22 patients with moderate to severe upper limb paresis 3-6 months post-onset. Patients in day hospital rehabilitation, receiving physical and occupational therapy 3 times weekly. The neuroprosthesis group used the device at home. The neuroprosthesis group had significantly greater improvements in spasticity, active range of motion and scores on the functional hand tests (those with partial active motion). Of the few patients with pain and oedema, there was improvement only among those in the neuroprosthesis group. There were no adverse reactions. Supplementing standard outpatient rehabilitation with daily home neuroprosthetic activation improves upper limb outcomes.

  8. Course of illness after the onset of chronic rejection in lung transplant recipients.

    PubMed

    Song, Mi-Kyung; De Vito Dabbs, Annette; Studer, Sean M; Zangle, Sarah E

    2008-05-01

    Despite the overall negative impact of chronic rejection on quality of life and survival after lung transplant, the specific clinical indicators of deterioration have not been identified. To describe the course of illness after the onset of chronic rejection, including demographic and transplant variables, morbidity, mortality, health resource utilization, and end-of-life care, and to identify clinical indicators of deterioration in health and limited survival after the onset of chronic rejection. The medical records of 311 recipients of lung transplants between 1998 and 2004 were reviewed retrospectively to identify 60 recipients who experienced chronic rejection. Median survival after chronic rejection was 31.34 months. Time to rejection (mean, 26.05 months; SD, 16.85) was significantly correlated with overall survival without need of a retransplant (r = 0.64; P < .001). The earlier the onset of chronic rejection or the need for oxygen at home, the shorter was the period of survival after chronic rejection and the more frequent were hospital and intensive care unit admissions and prolonged stays. Of the 26 recipients who died, 65% died at the transplant center, and all but 1 died in the intensive care unit; 3 died after multiple attempts of cardiopulmonary resuscitation; life support was ultimately withdrawn in 69%. Lung transplant recipients who experience chronic graft rejection have high rates of morbidity, mortality, and health resource utilization; however, the course of illness after chronic rejection is highly variable.

  9. Urinary C‑X‑C motif chemokine 13 is a noninvasive biomarker of antibody‑mediated renal allograft rejection.

    PubMed

    Chen, Dajin; Zhang, Jian; Peng, Wenhan; Weng, Chunhua; Chen, Jianghua

    2018-06-22

    Noninvasive monitoring methods of immune status are preferred by transplant recipients. The present study investigated whether urinary C‑X‑C motif chemokine 13 (CXCL13) had the potential to reflect ongoing immune processes within renal allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a total of 146 renal allograft recipients and 40 healthy controls at scheduled intervals and at the time of the indicated or protocol biopsy. The results of the present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal transplants compared with in those with acute tubular necrosis (ATN; P=0.001), chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001), which was associated with a good diagnostic performance for AR [area under the curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients with AR were also higher than that of patients with graft dysfunction but no rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished between acute antibody‑mediated rejection (ABMR) and acute cellular rejection, with an AUC of 0.856. Furthermore, patients with steroid‑resistant AR exhibited significantly increased urinary CXCL13/Cr levels than patients with reversible AR (P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first month of transplant were predictive of graft function at 3 and 6 months (P=0.044 and P=0.04, respectively). Collectively, the findings of the present study indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr levels predicted a poor response to steroid treatment and compromised graft function.

  10. Specimen rejection in laboratory medicine: Necessary for patient safety?

    PubMed

    Dikmen, Zeliha Gunnur; Pinar, Asli; Akbiyik, Filiz

    2015-01-01

    The emergency laboratory in Hacettepe University Hospitals receives specimens from emergency departments (EDs), inpatient services and intensive care units (ICUs). The samples are accepted according to the rejection criteria of the laboratory. In this study, we aimed to evaluate the sample rejection ratios according to the types of pre-preanalytical errors and collection areas. The samples sent to the emergency laboratory were recorded during 12 months between January to December, 2013 in which 453,171 samples were received and 27,067 specimens were rejected. Rejection ratios was 2.5% for biochemistry tests, 3.2% for complete blood count (CBC), 9.8% for blood gases, 9.2% for urine analysis, 13.3% for coagulation tests, 12.8% for therapeutic drug monitoring, 3.5% for cardiac markers and 12% for hormone tests. The most frequent rejection reasons were fibrin clots (28%) and inadequate volume (9%) for biochemical tests. Clotted samples (35%) and inadequate volume (13%) were the major causes for coagulation tests, blood gas analyses and CBC. The ratio of rejected specimens was higher in the EDs (40%) compared to ICUs (30%) and inpatient services (28%). The highest rejection ratio was observed in neurology ICU (14%) among the ICUs and internal medicine inpatient service (10%) within inpatient clinics. We detected an overall specimen rejection rate of 6% in emergency laboratory. By documentation of rejected samples and periodic training of healthcare personnel, we expect to decrease sample rejection ratios below 2%, improve total quality management of the emergency laboratory and promote patient safety.

  11. Specimen rejection in laboratory medicine: Necessary for patient safety?

    PubMed Central

    Dikmen, Zeliha Gunnur; Pinar, Asli; Akbiyik, Filiz

    2015-01-01

    Introduction The emergency laboratory in Hacettepe University Hospitals receives specimens from emergency departments (EDs), inpatient services and intensive care units (ICUs). The samples are accepted according to the rejection criteria of the laboratory. In this study, we aimed to evaluate the sample rejection ratios according to the types of pre-preanalytical errors and collection areas. Materials and methods The samples sent to the emergency laboratory were recorded during 12 months between January to December, 2013 in which 453,171 samples were received and 27,067 specimens were rejected. Results Rejection ratios was 2.5% for biochemistry tests, 3.2% for complete blood count (CBC), 9.8% for blood gases, 9.2% for urine analysis, 13.3% for coagulation tests, 12.8% for therapeutic drug monitoring, 3.5% for cardiac markers and 12% for hormone tests. The most frequent rejection reasons were fibrin clots (28%) and inadequate volume (9%) for biochemical tests. Clotted samples (35%) and inadequate volume (13%) were the major causes for coagulation tests, blood gas analyses and CBC. The ratio of rejected specimens was higher in the EDs (40%) compared to ICUs (30%) and inpatient services (28%). The highest rejection ratio was observed in neurology ICU (14%) among the ICUs and internal medicine inpatient service (10%) within inpatient clinics. Conclusions We detected an overall specimen rejection rate of 6% in emergency laboratory. By documentation of rejected samples and periodic training of healthcare personnel, we expect to decrease sample rejection ratios below 2%, improve total quality management of the emergency laboratory and promote patient safety. PMID:26527231

  12. 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

  13. Imaging mouse lung allograft rejection with (1)H MRI.

    PubMed

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

    2015-05-01

    To demonstrate that longitudinal, noninvasive monitoring via MRI can characterize acute cellular rejection in mouse orthotopic lung allografts. Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig versus anti-CD4/anti-CD8 treated groups. A two-dimensional multislice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at postoperative 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. Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 posttransplantation (0.046→0.789; P < 0.05), despite large intermouse 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. 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. © 2014 Wiley Periodicals, Inc.

  14. Magnetic resonance imaging findings in patients presenting with (sub)acute cerebellar ataxia.

    PubMed

    Schneider, Tanja; Thomalla, Götz; Goebell, Einar; Piotrowski, Anna; Yousem, David Mark

    2015-06-01

    Acute or subacute cerebellar inflammation is mainly caused by postinfectious, toxic, neoplastic, vascular, or idiopathic processes and can result in cerebellar ataxia. Previous magnetic resonance (MR) studies in single patients who developed acute or subacute ataxia showed varying imaging features. Eighteen patients presenting with acute and subacute onset of ataxia were included in this study. Cases of chronic-progressive/hereditary and noncerebellar causes (ischemia, multiple sclerosis lesions, metastasis, bleedings) were excluded. MR imaging findings were then matched with the clinical history of the patient. An underlying etiology for ataxic symptoms were found in 14/18 patients (postinfectious/infectious, paraneoplastic, autoimmune, drug-induced). In two of five patients without MR imaging findings and three of eight patients with minimal imaging features (cerebellar atrophy, slight signal alterations, and small areas of restricted diffusion), adverse clinical outcomes were documented. Of the five patients with prominent MR findings (cerebellar swelling, contrast enhancement, or broad signal abnormalities), two were lost to follow-up and two showed long-term sequelae. No correlation was found between the presence of initial MRI findings in subacute or acute ataxia patients and their long-term clinical outcome. MR imaging was more flagrantly positive in cases due to encephalitis.

  15. Dolutegravir-induced liver injury leading to sub-acute liver failure requiring transplantation: a case report and review of literature.

    PubMed

    Wang, Bo; Abbott, Laura; Childs, Kate; Taylor, Chris; Agarwal, Kosh; Cormack, Ian; Miquel, Rosa; Suddle, Abid

    2018-03-01

    A patient with human immunodeficiency virus-1 infection presented with sub-acute liver failure, temporally related to commencement of an antiretroviral therapy regimen containing dolutegravir (Triumeq). The patient was not a carrier of HLA-B5701, and abacavir hypersensitivity was unlikely. We believe this is the first report of severe dolutegravir-related hepatotoxicity resulting in sub-acute liver failure and transplantation and highlights a potential need for closer monitoring after drug initiation.

  16. 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. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  17. Presence of FoxP3+ regulatory T Cells predicts outcome of subclinical rejection of renal allografts.

    PubMed

    Bestard, Oriol; Cruzado, Josep M; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M

    2008-10-01

    Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens.

  18. Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts

    PubMed Central

    Bestard, Oriol; Cruzado, Josep M.; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M.

    2008-01-01

    Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens. PMID:18495961

  19. Remembering rejection: specificity and linguistic styles of autobiographical memories in borderline personality disorder and depression.

    PubMed

    Rosenbach, Charlotte; Renneberg, Babette

    2015-03-01

    High levels of rejection sensitivity are assumed to be the result of early and prolonged experiences of rejection. Aim of this study was to investigate autobiographical memories of rejection in clinical samples high in rejection sensitivity (Borderline Personality Disorder, BPD, and Major Depressive Disorder, MDD) and to identify group differences in the quality of the memories. Memories of rejection were retrieved using an adapted version of the Autobiographical Memory Test (AMT; five positive cue words, five cue words referring to rejection). Specificity of memories and linguistic word usage was analyzed in 30 patients with BPD, 27 patients with MDD and 30 healthy controls. Patients with BPD retrieved less specific memories compared to the healthy control group, whereas patients with MDD did not differ from controls in this regard. The group difference was no longer significant when controlling for rejection sensitivity. Linguistic analysis indicated that compared to both other groups, patients with BPD showed a higher self-focus, used more anger-related words, referred more frequently to social environments, and rated memories of rejection as more relevant for today's life. Clinical symptoms were not assessed in the control group. Moreover, the written form of the AMT might reduce the total number of specific memories. The level of rejection sensitivity influenced the specificity of the retrieved memories. Analysis of linguistic styles revealed specific linguistic patterns in BPD compared to non-clinical as well as depressed participants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. [Application of diffusion tensor imaging in judging infarction time of acute ischemic cerebral infarction].

    PubMed

    Dai, Zhenyu; Chen, Fei; Yao, Lizheng; Dong, Congsong; Liu, Yang; Shi, Haicun; Zhang, Zhiping; Yang, Naizhong; Zhang, Mingsheng; Dai, Yinggui

    2015-08-18

    To evaluate the clinical application value of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in judging infarction time phase of acute ischemic cerebral infarction. To retrospective analysis DTI images of 52 patients with unilateral acute ischemic cerebral infarction (hyper-acute, acute and sub-acute) from the Affiliated Yancheng Hospital of Southeast University Medical College, which diagnosed by clinic and magnetic resonance imaging. Set the regions of interest (ROIs) of infarction lesions, brain tissue close to infarction lesions and corresponding contra (contralateral normal brain tissue) on DTI parameters mapping of fractional anisotropy (FA), volume ratio anisotropy (VRA), average diffusion coefficient (DCavg) and exponential attenuation (Exat), record the parameters values of ROIs and calculate the relative parameters value of infarction lesion to contra. Meanwhile, reconstruct the DTT images based on the seed points (infarction lesion and contra). The study compared each parameter value of infarction lesions, brain tissue close to infarction lesions and corresponding contra, also analysed the differences of relative parameters values in different infarction time phases. The DTT images of acute ischemic cerebral infarction in each time phase could show the manifestation of fasciculi damaged. The DCavg value of cerebral infarction lesions was lower and the Exat value was higher than contra in each infarction time phase (P<0.05). The FA and VRA value of cerebral infarction lesions were reduced than contra only in acute and sub-acute infarction (P<0.05). The FA, VRA and Exat value of brain tissue close to infarction lesions were increased and DCavg value was decreased than contra in hyper-acute infarction (P<0.05). There were no statistic differences of FA, VRA, DCavg and Exat value of brain tissue close to infarction lesions in acute and sub-acute infarction. The relative FA and VRA value of infarction lesion to contra gradually

  1. Interleukin-10-1082 G/a polymorphism and acute renal graft rejection: a meta-analysis.

    PubMed

    Hu, Qiongwen; Tian, Hua; Wu, Qing; Li, Jun; Cheng, Xiaocheng; Liao, Pu

    2016-01-01

    The aim of this study was to investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in renal transplant recipients. We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register from the inception to March 2015 for relevant studies. Data concerning publication information, population characteristics, and transplant information were extracted. Odds ratios (ORs) was calculated for the association between IL-10-1082 GG genotype (or IL-10-1082 G allele) and AR risk. This meta-analysis included 22 case-control studies including 2779 cases of renal transplant recipients. The pooled estimate showed that the IL-10-1082 GG genotype was not significantly associated with AR risk (ORrandom=1.07, 95% CI 0.80-1.43, p = 0.64). Similarly, the pooled estimate showed that the IL-10-1082 G allele was not significantly associated with AR risk (ORfixed=1.02, 95% CI 0.90-1.16, p = 0.74). None of subgroup analyses yielded significant results in the association between IL-10-1082 GG genotype (or IL-10-1082 G allele) and AR risk. Meta-regression confirmed that there was no significant correlation between the pre-selected trial characteristics and our study results. This meta-analysis suggests that IL-10-1082 G/A polymorphism is not significantly associated with AR risk in renal transplant recipients.

  2. Rejection sensitivity moderates the impact of rejection on self-concept clarity.

    PubMed

    Ayduk, Ozlem; Gyurak, Anett; Luerssen, Anna

    2009-11-01

    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.

  3. Raman Spectroscopy Detects Cardiac Allograft Rejection with Molecular Specificity

    PubMed Central

    Chung, Yoon Gi; Tu, Qiang; Cao, Dianjun; Harada, Shuko; Eisen, Howard J; Chang, Chang

    2009-01-01

    Abstract Spatially resolved Raman spectroscopy is shown here to be capable of molecular‐specific detection without exogenous labeling. This molecular specificity is achieved by detecting the strong and characteristic Raman spectral signature of an indole derivative, serotonin, whose selective existence in rejected heart transplants serves as the biomarker. The study also corroborates the increasingly recognized role of serotonin receptors in various immune responses, including cardiac allograft rejection. Combining both medical and physical sciences, this work demonstrates the potential use of Raman spectroscopy in replacing the invasive endomyocardial biopsy as the standard for post‐transplantation rejection surveillance and presents a new paradigm in advancing clinical care through interdisciplinary studies. PMID:20443894

  4. Use of a SQUID array to detect T-cells with magnetic nanoparticles in determining transplant rejection

    NASA Astrophysics Data System (ADS)

    Flynn, Edward R.; Bryant, H. C.; Bergemann, Christian; Larson, Richard S.; Lovato, Debbie; Sergatskov, Dmitri A.

    2007-04-01

    Acute rejection in organ transplant is signaled by the proliferation of T-cells that target and kill the donor cells requiring painful biopsies to detect rejection onset. An alternative non-invasive technique is proposed using a multi-channel superconducting quantum interference device (SQUID) magnetometer to detect T-cell lymphocytes in the transplanted organ labeled with magnetic nanoparticles conjugated to antibodies specifically attached to lymphocytic ligand receptors. After a magnetic field pulse, the T-cells produce a decaying magnetic signal with a characteristic time of the order of a second. The extreme sensitivity of this technique, 10 5 cells, can provide early warning of impending transplant rejection and monitor immune-suppressive chemotherapy.

  5. Cognitive activity limitations one year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury.

    PubMed

    Sommer, Jens Bak; Norup, Anne; Poulsen, Ingrid; Morgensen, Jesper

    2013-09-01

    To examine cognitive activity limitations and predictors of outcome 1 year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury. The study included 119 patients with severe traumatic brain injury admitted to centralized sub-acute rehabilitation in the Eastern part of Denmark during a 5-year period from 2005 to 2009. Level of consciousness was assessed consecutively during rehabilitation and at 1 year post-trauma. Severity of traumatic brain injury was classified according to duration of post-traumatic amnesia. The cognitive subscale of Functional Independence MeasureTM (Cog-FIM) was used to assess cognitive activity limitations. Multivariate logistic regression analyses were performed to identify predictors of an independent level of functioning. The majority of patients progressed to a post-confusional level of consciousness during the first year post-trauma. At follow-up 33-58% of patients had achieved functional independence within the cognitive domains on the Cog-FIM. Socio-economic status, duration of acute care and post-traumatic amnesia were significant predictors of outcome. Substantial recovery was documented among patients with severe traumatic brain injury during the first year post-trauma. The results of the current study suggest that absence of consciousness at discharge from acute care should not preclude patients from being referred to specialized sub-acute rehabilitation.

  6. Intermediate-term graft loss after renal transplantation is associated with both donor-specific antibody and acute rejection.

    PubMed

    Devos, Jennifer M; Gaber, Ahmed Osama; Teeter, Larry D; Graviss, Edward A; Patel, Samir J; Land, Geoffrey A; Moore, Linda W; Knight, Richard J

    2014-03-15

    Renal transplant recipients with de novo DSA (dDSA) experience higher rates of rejection and worse graft survival than dDSA-free recipients. This study presents a single-center review of dDSA monitoring in a large, multi-ethnic cohort of renal transplant recipients. The authors performed a nested case-control study of adult kidney and kidney-pancreas recipients from July 2007 through July 2011. Cases were defined as dDSA-positive whereas controls were all DSA-negative transplant recipients. DSA were determined at 1, 3, 6, 9, and 12 months posttransplant, and every 6 months thereafter. Of 503 recipients in the analysis, 24% developed a dDSA, of whom 73% had dDSA against DQ antigen. Median time to dDSA was 6.1 months (range 0.2-44.6 months). After multivariate analysis, African American race, kidney-pancreas recipient, and increasing numbers of human leukocyte antigen mismatches were independent risk factors for dDSA. Recipients with dDSA were more likely to suffer an acute rejection (AR) (35% vs. 10%, P<0.001), an antibody-mediated AR (16% vs. 0.3%, P<0.001), an AR ascribed to noncompliance (8% vs. 2%, P=0.001), and a recurrent AR (6% vs. 1%, P=0.002) than dDSA-negative recipients. At a median follow-up of 31 months, the death-censored actuarial graft survival of dDSA recipients was worse than the DSA-free cohort (P=0.002). Yet, for AR-free recipients, there was no difference in graft survival between cohorts (P=0.66). Development of dDSA was associated with an increased incidence of graft loss, yet the detrimental effect of dDSA was limited in the intermediate term to recipients with AR.

  7. PAs and NPs in an emergency room-linked acute care clinic.

    PubMed

    Currey, C J

    1984-12-01

    The use of hospital emergency rooms for nonurgent care during evenings hours often strains medical resources and may affect the quality of emergency care. One facility's effective use of an after-hours acute care clinic staffed by PAs and NPs to divert nonurgent problems away from its emergency room is outlined. PAs and NPs work during peak demand hours (evenings and weekends) under the supervision of an emergency room physician, and receive supplementary support from other emergency room personnel. Incoming patients are referred to the emergency room or acute care clinic, depending on the nature of their problems. Acute care clinic patients are then treated by the PA or NP and either released or referred to an emergency room physician, if their conditions warrant additional treatment. As a result, use of the acute care clinic has greatly reduced the amount of non-urgent medical treatment in the emergency room and has provided other advantages to both patients and staff as well. These advantages and the encouraging statistics following six months of the clinic's operation are discussed.

  8. Atypical anticipatory postural adjustments during gait initiation among individuals with sub-acute stroke.

    PubMed

    Rajachandrakumar, Roshanth; Fraser, Julia E; Schinkel-Ivy, Alison; Inness, Elizabeth L; Biasin, Lou; Brunton, Karen; McIlroy, William E; Mansfield, Avril

    2017-02-01

    Anticipatory postural adjustments, executed prior to gait initiation, help preserve lateral stability when stepping. Atypical patterns of anticipatory activity prior to gait initiation may occur in individuals with unilateral impairment (e.g., stroke). This study aimed to determine the prevalence, correlates, and consequences of atypical anticipatory postural adjustment patterns prior to gait initiation in a sub-acute stroke population. Forty independently-ambulatory individuals with sub-acute stroke stood on two force plates and initiated gait at a self-selected speed. Medio-lateral centre of pressure displacement was calculated and used to define anticipatory postural adjustments (shift in medio-lateral centre of pressure >10mm from baseline). Stroke severity, motor recovery, and functional balance and mobility status were also obtained. Three patterns were identified: single (typical), absent (atypical), and multiple (atypical) anticipatory postural adjustments. Thirty-five percent of trials had atypical anticipatory postural adjustments (absent and multiple). Frequency of absent anticipatory postural adjustments was negatively correlated with walking speed. Multiple anticipatory postural adjustments were more prevalent when leading with the non-paretic than the paretic limb. Trials with multiple anticipatory postural adjustments had longer duration of anticipatory postural adjustment and time to foot-off, and shorter unloading time than trials with single anticipatory postural adjustments. A high prevalence of atypical anticipatory control prior to gait initiation was found in individuals with stroke. Temporal differences were identified with multiple anticipatory postural adjustments, indicating altered gait initiation. These findings provide insight into postural control during gait initiation in individuals with sub-acute stroke, and may inform interventions to improve ambulation in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Proposed Clinical Decision Rules to Diagnose Acute Rhinosinusitis Among Adults in Primary Care.

    PubMed

    Ebell, Mark H; Hansen, Jens Georg

    2017-07-01

    To reduce inappropriate antibiotic prescribing, we sought to develop a clinical decision rule for the diagnosis of acute rhinosinusitis and acute bacterial rhinosinusitis. Multivariate analysis and classification and regression tree (CART) analysis were used to develop clinical decision rules for the diagnosis of acute rhinosinusitis, defined using 3 different reference standards (purulent antral puncture fluid or abnormal finding on a computed tomographic (CT) scan; for acute bacterial rhinosinusitis, we used a positive bacterial culture of antral fluid). Signs, symptoms, C-reactive protein (CRP), and reference standard tests were prospectively recorded in 175 Danish patients aged 18 to 65 years seeking care for suspected acute rhinosinusitis. For each reference standard, we developed 2 clinical decision rules: a point score based on a logistic regression model and an algorithm based on a CART model. We identified low-, moderate-, and high-risk groups for acute rhinosinusitis or acute bacterial rhinosinusitis for each clinical decision rule. The point scores each had between 5 and 6 predictors, and an area under the receiver operating characteristic curve (AUROCC) between 0.721 and 0.767. For positive bacterial culture as the reference standard, low-, moderate-, and high-risk groups had a 16%, 49%, and 73% likelihood of acute bacterial rhinosinusitis, respectively. CART models had an AUROCC ranging from 0.783 to 0.827. For positive bacterial culture as the reference standard, low-, moderate-, and high-risk groups had a likelihood of acute bacterial rhinosinusitis of 6%, 31%, and 59% respectively. We have developed a series of clinical decision rules integrating signs, symptoms, and CRP to diagnose acute rhinosinusitis and acute bacterial rhinosinusitis with good accuracy. They now require prospective validation and an assessment of their effect on clinical and process outcomes. © 2017 Annals of Family Medicine, Inc.

  10. [Clinical studies on flomoxef in acute tonsillitis].

    PubMed

    Tomiyama, M

    1994-09-01

    To objectively evaluate the clinical efficacy and safety in acute tonsillitis, flomoxef (FMOX) was examined for the distribution of sensitivity of clinical strains to it and for its clinical usefulness. 1. The 80% minimum inhibitory concentration of 11 clinical strains of Gram-positive bacteria, 6 of Gram-negative bacteria and 5 of anaerobic bacteria was 0.39 microgram/ml. FMOX showed the strongest, most comprehensive antibacterial action among the drugs tested. 2. Thirty patients received FMOX. Clinical effectiveness was evaluated in 28 patients, and clinical usefulness and safety in 30. 3. The clinical efficacy rate ('excellent' and 'good') was 75% (21/28). 4. As for bacteriological response, bacterial elimination rates were 67% for Gram-positive bacteria, 100% for Gram-negative bacteria, 100% for anaerobic bacteria and 100% for mixed infections. 5. Side effects occurred in 2 (6%) patients: drug eruption and diarrhea in 1 patient each. These symptoms improved rapidly after discontinuation of the drug. 6. Although abnormal clinical test results were found in 7 (23%) patients, i.e., increases in GOT and GPT in 2, in GPT in 4 and in BUN in 1, they were transient. 7. The usefulness of FMOX was assessed in light of its efficacy and safety. It was highly satisfactory in 14 patients, satisfactory in 11, relatively satisfactory in 1, unsatisfactory in 2 and highly unsatisfactory in 2, and rate of usefulness was 83%. FMOX is considered to be highly useful for the treatment of severe acute tonsillitis.

  11. A Business Case Analysis: Establishment of a Sub-Acute Ward for Tripler Army Medical Center

    DTIC Science & Technology

    2007-03-31

    7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) S. PERFORMING ORGANIZATION REPORT Tripler Army Medical Center I Jarrett White Road TAMC, Hawaii ...Reichenberg, CHES Tripler Army Medical Center, Hawaii Date Complete: 31 March 2007 Date Submitted: 31 March 2007 Running Heading: Establishment of a Sub... Hawaii for his personal insight. Running Heading: Establishment of a Sub-Acute Ward 4 Abstract This business case examines the likely costs and

  12. [Synchronous acute cholecystolithiasis and perforated acute appendicitis. Case report].

    PubMed

    Padrón-Arredondo, Guillermo; de Atocha Rosado-Montero, Manuel

    2016-01-01

    Acute appendicitis and acute cholecystitis are among the most common diagnoses that general surgeons operate on. However, it is rarely described in its synchronous form. A 43 year-old woman attending the clinic for right upper quadrant pain of 11 days duration. The patient refers to intermittent radiating pain in the right side, with positive Murphy, tachycardia, and fever. The laboratory results showed white cells 16,200/mm(3), glucose 345 mg/dl, abnormal liver function tests. Acute cholecystitis was reported with ultrasound. A Masson-type incision was made, noting an enlarged pyogenic gallbladder with thickened walls, sub-hepatic abscess of approximately 300 ml, greenish-yellow colour, and foetid. An anterograde subtotal cholecystectomy is performed due to difficulty in identifying elements of Calot triangle due to the inflammatory process, opening it and extracting stones. The right iliac fossa is reviewed, finding a plastron and a sub-serous retrocaecal appendix perforated in its middle third with free fecalith and an abscess in the pelvic cavity. An anterograde appendectomy was performed and the patient progressed satisfactorily, later being discharged due to improvement. In this patient, with a history of recurrent episodes of gallbladder pain and disseminated acute abdominal pain without peritoneal irritation, clinical suspicion was exacerbated cholecystitis with probable empyema of the gallbladder. Open surgery approach for this patient allowed access to both the appendix and gallbladder in order to perform a complete exploration of the abdominal cavity. The synchronous presentation of cholecystolithiasis and complicated appendicitis has not been reported in the literature. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  13. Demographic and clinical profiles in patients with acute urticaria.

    PubMed

    Sánchez-Borges, M; Capriles-Hulett, A; Caballero-Fonseca, F

    2015-01-01

    Urticaria is a common cause for consultation in general and specialised medical practices. There is scarce information on the characteristics of patients suffering acute urticaria in Latin America. To investigate demographic and clinical features of patients with acute urticaria attending two allergy clinics in Caracas, Venezuela. A prospective study of all new patients who consulted during a three-year period because of acute urticaria. Information on age, gender, symptom duration, previous medical history, body distribution of wheals and angio-oedema, laboratory investigations, skin prick tests, and pharmacological treatment, was collected. Patients were classified according to their age as children/adolescents and adults. Two hundred and forty eight patients (177 adults and 71 children) were studied. Acute urticaria was more frequent in middle-aged atopic female patients. Lesions more often involved upper and lower limbs and head, and 31% of patients exhibited generalised urticaria. Laboratory investigations, performed only in selected cases, did not contribute to the final diagnosis. Most frequent subtypes of acute urticaria were spontaneous, dermographic, papular, and drug-induced urticaria. Most patients were treated with non-sedating antihistamines, with increased use of cetirizine and levocetirizine in children, while 5.6% of children and 20.3% of adults required the addition of short courses of systemic corticosteroids. Acute urticaria is a frequent cause of consultation for allergists, affecting more often middle-aged female atopic patients. The use of extensive complementary tests does not seem to be cost-effective for this clinical condition. Spontaneous, dermographic, papular and drug-induced urticaria are the most common subtypes. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  14. Antibody-Mediated Rejection of Human Orthotopic Liver Allografts

    PubMed Central

    Demetris, A. Jake; Jaffe, Ron; Tzakis, A.; Ramsey, Glenn; Todo, S.; Belle, Steven; Esquivel, Carlos; Shapiro, Ron; Markus, Bernd; Mroczek, Elizabeth; Van Thiel, D. H.; Sysyn, Greg; Gordon, Robert; Makowka, Leonard; Starzl, Tom

    1988-01-01

    A clinicopathologic analysis of liver transplantation across major ABO blood group barriers was carried out 1) to determine if antibody-mediated (humoral) rejection was a cause of graft failure and if humoral rejection can be identified, 2) to propose criteria for establishing the diagnosis, and 3) to describe the clinical and pathologic features of humoral rejection. A total of 51 (24 primary) ABO-incompatible (ABO-I) liver grafts were transplanted into 49 recipients. There was a 46% graft failure rate during the first 30 days for primary ABO-I grafts compared with an 11% graft failure rate for primary ABO compatible (ABO-C), crossmatch negative, age, sex and priority-matched control patients (P < 0.02). A similarly high early graft failure rate (60%) was seen for nonprimary ABO-I grafts during the first 30 days. Clinically, the patients experienced a relentless rise in serum transaminases, hepatic failure, and coagulopathy during the first weeks after transplant. Pathologic examination of ABO-I grafts that failed early demonstrated widespread areas of geographic hemorrhagic necrosis with diffuse intraorgan coagulation. Prominent arterial deposition of antibody and complement components was demonstrated by immunoflourescent staining. Elution studies confirmed the presence of tissue-bound, donor-specific isoagglutinins within the grafts. No such deposition was seen in control cases. These studies confirm that antibody mediated rejection of the liver occurs and allows for the development of criteria for establishing the diagnosis. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:3046369

  15. Sub-clinical assessment of atopic dermatitis severity using angiographic optical coherence tomography

    PubMed Central

    Byers, Robert A.; Maiti, Raman; Danby, Simon G.; Pang, Elaine J.; Mitchell, Bethany; Carré, Matt J.; Lewis, Roger; Cork, Michael J.; Matcher, Stephen J.

    2018-01-01

    Measurement of sub-clinical atopic dermatitis (AD) is important for determining how long therapies should be continued after clinical clearance of visible AD lesions. An important biomarker of sub-clinical AD is epidermal hypertrophy, the structural measures of which often make optical coherence tomography (OCT) challenging due to the lack of a clearly delineated dermal-epidermal junction in AD patients. Alternatively, angiographic OCT measurements of vascular depth and morphology may represent a robust biomarker for quantifying the severity of clinical and sub-clinical AD. To investigate this, angiographic data sets were acquired from 32 patients with a range of AD severities. Deeper vascular layers within skin were found to correlate with increasing clinical severity. Furthermore, for AD patients exhibiting no clinical symptoms, the superficial plexus depth was found to be significantly deeper than healthy patients at both the elbow (p = 0.04) and knee (p<0.001), suggesting that sub-clinical changes in severity can be detected. Furthermore, the morphology of vessels appeared altered in patients with severe AD, with significantly different vessel diameter, length, density and fractal dimension. These metrics provide valuable insight into the sub-clinical severity of the condition, allowing the effects of treatments to be monitored past the point of clinical remission. PMID:29675335

  16. Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders*

    PubMed Central

    Calfee, Carolyn S.; Eisner, Mark D.; Ware, Lorraine B.; Thompson, B. Taylor; Parsons, Polly E.; Wheeler, Arthur P.; Korpak, Anna; Matthay, Michael A.

    2009-01-01

    Objective Patients with trauma-associated acute lung injury have better outcomes than patients with other clinical risks for lung injury, but the mechanisms behind these improved outcomes are unclear. We sought to compare the clinical and biological features of patients with trauma-associated lung injury with those of patients with other risks for lung injury and to determine whether the improved outcomes of trauma patients reflect their baseline health status or less severe lung injury, or both. Design, Setting, and Patients Analysis of clinical and biological data from 1,451 patients enrolled in two large randomized, controlled trials of ventilator management in acute lung injury. Measurements and Main Results Compared with patients with other clinical risks for lung injury, trauma patients were younger and generally less acutely and chronically ill. Even after adjusting for these baseline differences, trauma patients had significantly lower plasma levels of intercellular adhesion molecule-1, von Willebrand factor antigen, surfactant protein-D, and soluble tumor necrosis factor receptor-1, which are biomarkers of lung epithelial and endothelial injury previously found to be prognostic in acute lung injury. In contrast, markers of acute inflammation, except for interleukin-6, and disordered coagulation were similar in trauma and nontrauma patients. Trauma-associated lung injury patients had a significantly lower odds of death at 90 days, even after adjusting for baseline clinical factors including age, gender, ethnicity, comorbidities, and severity of illness (odds ratio, 0.44; 95% confidence interval, 0.24 – 0.82; p = .01). Conclusions Patients with trauma-associated lung injury are less acutely and chronically ill than other lung injury patients; however, these baseline clinical differences do not adequately explain their improved outcomes. Instead, the better outcomes of the trauma population may be explained, in part, by less severe lung epithelial and

  17. Interleukin-10-1082G/A polymorphism and acute liver graft rejection: A meta-analysis

    PubMed Central

    Liu, Fei; Li, Bo; Wang, Wen-Tao; Wei, Yong-Gang; Yan, Lv-Nan; Wen, Tian-Fu; Xu, Ming-Qing; Yang, Jia-Yin

    2012-01-01

    AIM: To investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in liver transplant (LT) recipients. METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% CIs for IL-10-1082 G/A polymorphism and AR were calculated in a fixed- and a random-effects model as appropriate. RESULTS: This meta-analysis included seven case-control studies, which comprised 652 cases of LT recipients in which 241 cases developed AR and 411 cases did not develop AR. Overall, the variant A allele was not associated with AR risk when compared with the wild-type G allele (OR = 0.94, 95% CI: 0.64-1.39). Moreover, similar results were observed when the AA genotype was compared with the AG/GG genotype (OR = 1.05, 95% CI: 0.55-2.02). When stratifying for ethnicity, no significant association was observed among either Caucasians or Asians. Because only one study was performed in Asian patients, the result of subgroup analysis by ethnicity would not be reliable for Asians. Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. CONCLUSION: This meta-analysis suggests that IL-10-1082 G/A polymorphism may be not associated with AR risk in LT recipients among Caucasians. PMID:22371646

  18. Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

    PubMed

    Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

    2013-01-01

    The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications. Copyright © 2012 Wiley Periodicals, Inc.

  19. Clinical diagnostic accuracy of acute colonic diverticulitis in patients admitted with acute abdominal pain, a receiver operating characteristic curve analysis.

    PubMed

    Jamal Talabani, A; Endreseth, B H; Lydersen, S; Edna, T-H

    2017-01-01

    The study investigated the capability of clinical findings, temperature, C-reactive protein (CRP), and white blood cell (WBC) count to discern patients with acute colonic diverticulitis from all other patients admitted with acute abdominal pain. The probability of acute diverticulitis was assessed by the examining doctor, using a scale from 0 (zero probability) to 10 (100 % probability). Receiver operating characteristic (ROC) curves were used to assess the clinical diagnostic accuracy of acute colonic diverticulitis in patients admitted with acute abdominal pain. Of 833 patients admitted with acute abdominal pain, 95 had acute colonic diverticulitis. ROC curve analysis gave an area under the ROC curve (AUC) of 0.95 (CI 0.92 to 0.97) for ages <65 years, AUC = 0.86 (CI 0.78 to 0.93) in older patients. Separate analysis showed an AUC = 0.83 (CI 0.80 to 0.86) of CRP alone. White blood cell count and temperature were almost useless to discriminate acute colonic diverticulitis from other types of acute abdominal pain, AUC = 0.59 (CI 0.53 to 0.65) for white blood cell count and AUC = 0.57 (0.50 to 0.63) for temperature, respectively. This prospective study demonstrates that standard clinical evaluation by non-specialist doctors based on history, physical examination, and initial blood tests on admission provides a high degree of diagnostic precision in patients with acute colonic diverticulitis.

  20. Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation.

    PubMed

    Bergler, Tobias; Jung, Bettina; Bourier, Felix; Kühne, Louisa; Banas, Miriam C; Rümmele, Petra; Wurm, Simone; Banas, Bernhard

    2016-01-01

    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. 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. 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 initiation. There is a robust

  1. 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

  2. Use of OKT3 with Ciclosporin and Steroids for Reversal of Acute Kidney and Liver Allograft Rejection 1

    PubMed Central

    Fung, John J.; Demetris, A. Jake; Porter, Kendrick A.; Iwatsuki, Shunzaburo; Gordon, Robert D.; Esquivel, Carlos O.; Jaffe, Ronald; Tzakis, Andreas; Shaw, Byers W.; Starzl, Thomas E.

    2010-01-01

    OKT3 monoclonal antibody therapy was added to preexisting baseline immunosuppressive treatment with ciclosporin and steroids to treat rejection in 52 recipients of cadaveric livers and 10 recipients of cadaveric kidneys. Rejection was controlled in 75% of patients treated, often after high-dose steroid therapy had failed. Rejection recurred during the 17-month follow-up period, after completion of OKT3, in only 25% of the patients who had responded. The safety and effectiveness of this monoclonal therapy, added to ciclosporin and steroids, has been established in this study. PMID:3306422

  3. Position statement. The right to accept or reject an assignment. American Nurses Association.

    PubMed

    1996-01-01

    The American Nurses Association (ANA) believes that nurses should reject assignment that puts patients or themselves in serious, immediate jeopardy. ANA supports the nurses obligation to reject an assignment in these situations even where there is not a specific legal protection for rejecting such an assignment. The professional obligations to the nurse to safeguard clients are grounded in the ethical norms of the profession, the Standards of Clinical Nursing Practice and state nurse practice acts.

  4. [Level of Development of Clinical Ethics Consultation in Psychiatry - Results of a Survey Among Psychiatric Acute Clinics and Forensic Psychiatric Hospitals].

    PubMed

    Gather, Jakov; Kaufmann, Sarah; Otte, Ina; Juckel, Georg; Schildmann, Jan; Vollmann, Jochen

    2018-04-17

    The aim of this article is to assess the level of development of clinical ethics consultation in psychiatric institutions in North Rhine-Westphalia. Survey among medical directors, directors of nursing and administrative directors of all psychiatric acute clinics and forensic psychiatric hospitals in North Rhine-Westphalia. 113 persons working in psychiatric acute clinics responded (reponse rate: 48 %) and 13 persons working in forensic psychiatric hospitals (response rate 54 %). We received at least one response from 89 % of all psychiatric acute clinics and from 100 % of all forensic psychiatric hospitals. 90 % of the responding psychiatric acute clinics and 29 % of the responding forensic psychiatric hospitals have already implemented clinical ethics consultation. Clinical ethics consultation is more widespread in psychiatric institutions than was hitherto assumed. Future medical ethics research should therefore give greater attention to the methodology and the quality of clinical ethics consultation in psychiatric practice. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Endoscope-assisted, minimally invasive evacuation of sub-acute/chronic epidural hematoma: Novelty or paradox of Theseus?

    PubMed

    Ansari, Ishtyaque; Futane, Sameer; Ansari, Ashfaque

    2016-08-01

    Sub-acute/chronic epidural hematoma (EDH) may present with nagging symptoms of headache, nausea, vomiting, lethargy, etc. We attempted to offer a minimally invasive, single burr hole, endoscope-assisted evacuation of EDHs instead of a conventional craniotomy. Seven patients with sub-acute/chronic EDH (six supratentorial and one infratentorial) presented to us 3 to 7 days after low-velocity road traffic accidents with complaints of headache and lethargy. The EDH volumes measured between 20 to 50 ml, and the patients were operated on using a single burr hole made through a small incision. We used 0-, 30- and 70-degree, angulated, rigid, high-definition endoscopes to identify and evacuate the organized clots in the extradural space. Flexible catheters were used for suction and irrigation. After achieving hemostasis, the dura was hitched back to the burr hole site. The wound was closed over a negative suction drain. All patients had prompt recovery from symptoms. Postoperative CT scans showed complete or near complete evacuation of the hematomas. The hospital stay and analgesic requirements were minimal. There was no infective complication or conversion to conventional open surgery. The average time for surgery was 77.8 min, and average blood loss was 328.5 ml. Endoscope-assisted evacuation of sub-acute/chronic EDH is a novel concept, which offers quick relief from symptoms in a minimally invasive fashion and a cosmetically acceptable way. None of the standard principles of surgery are hampered. It avoids extensive dissection of the temporalis or sub-occipital muscles. However, achieving hemostasis can be difficult. Further study and better equipment will validate the procedure.

  6. Why do we do as we do? Factors influencing clinical reasoning and decision-making among physiotherapists in an acute setting.

    PubMed

    Holdar, Ulrika; Wallin, Lars; Heiwe, Susanne

    2013-12-01

    Despite the current movement for health-care to become more informed by evidence, knowledge on effective implementation of evidence-based practice is scarce. To improve research application among physiotherapists, the process of implementation and clinical reasoning needs to be scrutinized. The aim of this study was to identify various experiences of factors that influence the physiotherapist's clinical reasoning in specialist care. A phenomenographic approach was chosen. Eleven physiotherapists at two acute care hospitals in nn. Data was obtained by observations and interviews. Phenomenographic data analysis identified various experiences of clinical decision-making. The Ethical Review Board of the nn approved the study. The observations and the interviews enabled identification of various experiences that influenced clinical decision-making. The physiotherapists' clinical reasoning was perceived to be constrained by contextual factors. The physiotherapists collected current information on the patient by using written and verbal information exchange and used this to generate an inner picture of the patient. By creating hypotheses that were accepted or rejected, they made decisions in advance of their interventions. The decisions were influenced by the individual characteristics of the physiotherapist, his/her knowledge and patient perceptions. Clinical reasoning is a complex and constantly evolving process. Contextual factors such as economy and politics are not easily changed, but factors such as the patient and the physiotherapist as a person are more tangible. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Help seeking behavior and onset-to-alarm time in patients with acute stroke: sub-study of the preventive antibiotics in stroke study.

    PubMed

    Zock, E; Kerkhoff, H; Kleyweg, R P; van Bavel-Ta, T B V; Scott, S; Kruyt, N D; Nederkoorn, P J; van de Beek, D

    2016-11-25

    Patients with acute stroke often do not seek immediate medical help, which is assumed to be driven by lack of knowledge of stroke symptoms. We explored the process of help seeking behavior in patients with acute stroke, evaluating knowledge about stroke symptoms, socio-demographic and clinical characteristics, and onset-to-alarm time (OAT). In a sub-study of the Preventive Antibiotics in Stroke Study (PASS), 161 acute stroke patients were prospectively included in 3 Dutch hospitals. A semi-structured questionnaire was used to assess knowledge, recognition and interpretation of stroke symptoms. With in-depth interviews, response actions and reasons were explored. OAT was recorded and associations with socio-demographic, clinical parameters were assessed. Knowledge about stroke symptoms does not always result in correct recognition of own stroke symptoms, neither into correct interpretation of the situation and subsequent action. In our study population of 161 patients with acute stroke, median OAT was 30 min (interquartile range [IQR] 10-150 min). Recognition of one-sided weakness and/or sensory loss (p = 0.046) and adequate interpretation of the stroke situation (p = 0.003), stroke at daytime (p = 0.002), severe stroke (p = 0.003), calling the emergency telephone number (p = 0.004), and transport by ambulance (p = 0.040) were associated with shorter OAT. Help seeking behavior after acute stroke is a complex process. A shorter OAT after stroke is associated with correct recognition of one-sided weakness and/or sensory loss, adequate interpretation of the stroke situation by the patient and stroke characteristics and logistics of stroke care, but not by knowledge of stroke symptoms.

  8. REJECTING PROPOSED DENSE MATTER EQUATIONS OF STATE WITH QUIESCENT LOW-MASS X-RAY BINARIES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guillot, Sebastien; Rutledge, Robert E., E-mail: guillots@physics.mcgill.ca, E-mail: rutledge@physics.mcgill.ca

    2014-11-20

    Neutrons stars are unique laboratories for discriminating between the various proposed equations of state of matter at and above nuclear density. One sub-class of neutron stars—those inside quiescent low-mass X-ray binaries (qLMXBs)—produce a thermal surface emission from which the neutron star radius (R {sub NS}) can be measured, using the widely accepted observational scenario for qLMXBs, assuming unmagnetized H atmospheres. In a combined spectral analysis, this work first reproduces a previously published measurement of the R {sub NS}, assumed to be the same for all neutron stars, using a slightly expanded data set. The radius measured is R{sub NS}=9.4±1.2 km.more » On the basis of spectral analysis alone, this measured value is not affected by imposing an assumption of causality in the core. However, the assumptions underlying this R {sub NS} measurement would be falsified by the observation of any neutron star with a mass >2.6 M {sub ☉}, since radii <11 km would be rejected if causality is assumed, which would exclude most of the R {sub NS} parameter space obtained in this analysis. Finally, this work directly tests a selection of dense matter equations of state: WFF1, AP4, MPA1, PAL1, MS0, and three versions of equations of state produced through chiral effective theory. Two of those, MS0 and PAL1, are rejected at the 99% confidence level, accounting for all quantifiable uncertainties, while the other cannot be excluded at >99% certainty.« less

  9. Clinical presentation of acute Q fever in lanzarote (Canary Islands): a 2-year prospective study.

    PubMed

    Pascual Velasco, F; Borobio Enciso, M V; González Lama, Z; Carrascosa Porras, M

    1996-01-01

    The clinical manifestations of acute Q fever may differ markedly from country to country. In this regard, fever and hepatitis seem to be the dominant clinical features of acute Coxiella burnetii infection in Lanzarote, Canary Islands. A possible interaction between environmental factors and some strains of C. burnetii could explain the different clinical presentations of acute Q fever.

  10. The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics*

    PubMed Central

    Sigdel, Tara K.; Salomonis, Nathan; Nicora, Carrie D.; Ryu, Soyoung; He, Jintang; Dinh, Van; Orton, Daniel J.; Moore, Ronald J.; Hsieh, Szu-Chuan; Dai, Hong; Thien-Vu, Minh; Xiao, Wenzhong; Smith, Richard D.; Qian, Wei-Jun; Camp, David G.; Sarwal, Minnie M.

    2014-01-01

    Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a “hub” protein for graft injury irrespective of causation. Sixty-nine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of

  11. Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish.

    PubMed

    Kovács, Róbert; Bakos, Katalin; Urbányi, Béla; Kövesi, Judit; Gazsi, Gyöngyi; Csepeli, Andrea; Appl, Ádám János; Bencsik, Dóra; Csenki, Zsolt; Horváth, Ákos

    2016-08-01

    The acute and sub-chronic effects of four cytostatic drugs-5-fluorouracil (5-FU), cisplatin (CisPt), etoposide (ET) and imatinib mesylate (IM)-on zebrafish (Danio rerio) were investigated. Acute tests were carried out in a static system in accordance with the OECD guideline 203 for adult fish and the draft guideline for fish embryos (FET test) in order to find the LC50 values of the four cytostatic drugs. Early-life stage toxicity test on zebrafish was conducted according the OECD guideline 210 using the cytostatic drugs 5-FU and IM in a semistatic system with the objective of investigating the sub-chronic effects of the cytostatic drugs on fish. In adult fish, the cytostatic drugs 5-FU and ET did not pass the limit test, thus, are considered non-toxic. In case of cisplatin, LC50 was calculated at 64.5 mg L(-1), whereas in case of IM, LC50 was at 70.8 mg L(-1). In the FET test, LC50 of 5-FU at 72-h post fertilization (hpf) was 2441.6 mg L(-1). In case of CisPt, LC50 was 349.9 mg L(-1) at 48 hpf and it progressively decreased to 81.3 mg L(-1) at 120 hpf. In addition, CisPt caused a significant delay in the hatch of larvae. In case of ET, LC50 values were not calculable as they were higher than 300 mg L(-1) at which concentration the substance crystallized in the solution. LC50 values of IM were 48 hpf; 158.3 mg L(-1) , 72 hpf; 141.6 mg L(-1), 96 hpf; 118.0 mg L(-1), and 120 hpf; 65.9 mg L(-1). In the Early-life Stage Test with 5-FU, embryonic deformities were not detected during the tests. Regarding mortalities, the 10 mg L(-1) concentration can be considered as LOEC, as statistically significant difference in mortalities was detected in this group alone. Concerning dry body weight and standard length, 1 mg L(-1) is the LOEC. In case of IM, the highest tested concentration (10 mg L(-1)) can be considered LOEC for mortalities, however, the treatment did not have an effect on the other investigated parameters (dry and wet weight, standard length). All four cytostatic

  12. The clinics of acute coronary syndrome

    PubMed Central

    Rastelli, Gianni

    2016-01-01

    Risk stratification and management of patients with chest pain continues to be challenging despite considerable efforts made in the last decades by many clinicians and researchers. The throutful evaluation necessitates that the physicians have a high index of suspicion for acute coronary syndrome (ACS) and always keep in mind the myriad of often subtle and atypical presentations of ischemic heart disease, especially in certain patient populations such as the elderly ones. In this article we aim to review and discuss the available evidence on the value of clinical presentation in patients with a suspected ACS, with special emphasis on history, characteristics of chest pain, associated symptoms, atypical presentations, precipitating and relieving factors, drugs, clinical rules and significance of clinical Gestalt. PMID:27294087

  13. Clinical practice guideline: management of acute pancreatitis

    PubMed Central

    Greenberg, Joshua A.; Hsu, Jonathan; Bawazeer, Mohammad; Marshall, John; Friedrich, Jan O.; Nathens, Avery; Coburn, Natalie; May, Gary R.; Pearsall, Emily; McLeod, Robin S.

    2016-01-01

    There has been an increase in the incidence of acute pancreatitis reported worldwide. Despite improvements in access to care, imaging and interventional techniques, acute pancreatitis continues to be associated with significant morbidity and mortality. Despite the availability of clinical practice guidelines for the management of acute pancreatitis, recent studies auditing the clinical management of the condition have shown important areas of noncompliance with evidence-based recommendations. This underscores the importance of creating understandable and implementable recommendations for the diagnosis and management of acute pancreatitis. The purpose of the present guideline is to provide evidence-based recommendations for the management of both mild and severe acute pancreatitis as well as the management of complications of acute pancreatitis and of gall stone–induced pancreatitis. Une hausse de l’incidence de pancréatite aiguë a été constatée à l’échelle mondiale. Malgré l’amélioration de l’accès aux soins et aux techniques d’imagerie et d’intervention, la pancréatite aiguë est toujours associée à une morbidité et une mortalité importantes. Bien qu’il existe des guides de pratique clinique pour la prise en charge de la pancréatite aiguë, des études récentes sur la vérification de la prise en charge clinique de cette affection révèlent des lacunes importantes dans la conformité aux recommandations fondées sur des données probantes. Ces résultats mettent en relief l’importance de formuler des recommandations compréhensibles et applicables pour le diagnostic et la prise en charge de la pancréatite aiguë. La présente ligne directrice vise à fournir des recommandations fondées sur des données probantes pour la prise en charge de la pancréatite aiguë, qu’elle soit bénigne ou grave, ainsi que de ses complications et de celles de la pancréatite causée par un calcul biliaire. PMID:27007094

  14. Clinical dehydration and glomerular filtration rate in acute paediatric gastroenteritis.

    PubMed

    Milani, Gregorio P; Fossali, Emilio F; Perri, Alessandra; Vettori, Arianna; Grillo, Paolo; Agostoni, Carlo

    2013-08-01

    To evaluate changes in glomerular filtration rate in acute gastroenteritis. The correlation between two clinical diagnostic scales and glomerular filtration rate has been investigated in 113 children with acute gastroenteritis in a paediatric emergency setting. A significant reduction of GFR was found in 10% children less than, and 5% children higher than, 2 years of age with acute gastroenteritis. The differences observed as for risk of renal hypoperfusion suggests to consider the age of children as an important determinant to consider the dehydration status in acute gastroenteritis. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  15. Integrated Kidney Exosome Analysis for the Detection of Kidney Transplant Rejection.

    PubMed

    Park, Jongmin; Lin, Hsing-Ying; Assaker, Jean Pierre; Jeong, Sangmoo; Huang, Chen-Han; Kurdi, A; Lee, Kyungheon; Fraser, Kyle; Min, Changwook; Eskandari, Siawosh; Routray, Sujit; Tannous, Bakhos; Abdi, Reza; Riella, Leonardo; Chandraker, Anil; Castro, Cesar M; Weissleder, Ralph; Lee, Hakho; Azzi, Jamil R

    2017-11-28

    Kidney transplant patients require life-long surveillance to detect allograft rejection. Repeated biopsy, albeit the clinical gold standard, is an invasive procedure with the risk of complications and comparatively high cost. Conversely, serum creatinine or urinary proteins are noninvasive alternatives but are late markers with low specificity. We report a urine-based platform to detect kidney transplant rejection. Termed iKEA (integrated kidney exosome analysis), the approach detects extracellular vesicles (EVs) released by immune cells into urine; we reasoned that T cells, attacking kidney allografts, would shed EVs, which in turn can be used as a surrogate marker for inflammation. We optimized iKEA to detect T-cell-derived EVs and implemented a portable sensing system. When applied to clinical urine samples, iKEA revealed high level of CD3-positive EVs in kidney rejection patients and achieved high detection accuracy (91.1%). Fast, noninvasive, and cost-effective, iKEA could offer new opportunities in managing transplant recipients, perhaps even in a home setting.

  16. Ion Exclusion by Sub 2-nm Carbon Nanotube Pores

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fornasiero, F; Park, H G; Holt, J K

    2008-04-09

    Carbon nanotubes offer an outstanding platform for studying molecular transport at nanoscale, and have become promising materials for nanofluidics and membrane technology due to their unique combination of physical, chemical, mechanical, and electronic properties. In particular, both simulations and experiments have proved that fluid flow through carbon nanotubes of nanometer size diameter is exceptionally fast compared to what continuum hydrodynamic theories would predict when applied on this length scale, and also, compared to conventional membranes with pores of similar size, such as zeolites. For a variety of applications such as separation technology, molecular sensing, drug delivery, and biomimetics, selectivity ismore » required together with fast flow. In particular, for water desalination, coupling the enhancement of the water flux with selective ion transport could drastically reduce the cost of brackish and seawater desalting. In this work, we study the ion selectivity of membranes made of aligned double-walled carbon nanotubes with sub-2 nm diameter. Negatively charged groups are introduced at the opening of the carbon nanotubes by oxygen plasma treatment. Reverse osmosis experiments coupled with capillary electrophoresis analysis of permeate and feed show significant anion and cation rejection. Ion exclusion declines by increasing ionic strength (concentration) of the feed and by lowering solution pH; also, the highest rejection is observed for the A{sub m}{sup Z{sub A}} C{sub n}{sup Z{sub C}} salts (A=anion, C=cation, z= valence) with the greatest Z{sub A}/Z{sub C} ratio. Our results strongly support a Donnan-type rejection mechanism, dominated by electrostatic interactions between fixed membrane charges and mobile ions, while steric and hydrodynamic effects appear to be less important. Comparison with commercial nanofiltration membranes for water softening reveals that our carbon nanotube membranes provides far superior water fluxes for similar ion

  17. Acute pancreatitis following scoliosis surgery: description and clinical course in 14 adolescents.

    PubMed

    El Bouyousfi, Maalik; Leveque, Christine; Miladi, Lotfi; Irtan, Sabine; Hamza, Jamil; Oualha, Mehdi

    2016-10-01

    Acute pancreatitis is a possible complication after scoliosis surgery. Although some risk factors have been documented in the literature, clinical description of pancreatitis diagnosis and ensuing course still remain very poor. The aim of this study was to describe characteristics of acute pancreatitis after scoliosis surgery. A descriptive, retrospective and single-center study of fourteen adolescents with postoperative acute pancreatitis after spine fusion surgery in scoliosis management between April 2003 and August 2012 was performed. Acute pancreatitis occurred within 9.5 days (4-51) after surgery. Abdominal pain was atypical and was expressed in only half of the children. Ileus, nausea and vomiting were the most frequent signs. None of the acute pancreatitis cases was severe. Acute pancreatitis is an early complication of scoliosis surgery. Clinical signs are atypical and non-severe and can induce misleading forms. Presence of delayed digestive problems should alert the clinician to the risk of pancreatitis in the aftermath of scoliosis surgery.

  18. Spontaneous Swallow Frequency Compared with Clinical Screening in the Identification of Dysphagia in Acute Stroke

    PubMed Central

    Crary, Michael A.; Carnaby, Giselle D.; Sia, Isaac

    2017-01-01

    Background The aim of this study was to compare spontaneous swallow frequency analysis (SFA) with clinical screening protocols for identification of dysphagia in acute stroke. Methods In all, 62 patients with acute stroke were evaluated for spontaneous swallow frequency rates using a validated acoustic analysis technique. Independent of SFA, these same patients received a routine nurse-administered clinical dysphagia screening as part of standard stroke care. Both screening tools were compared against a validated clinical assessment of dysphagia for acute stroke. In addition, psychometric properties of SFA were compared against published, validated clinical screening protocols. Results Spontaneous SFA differentiates patients with versus without dysphagia after acute stroke. Using a previously identified cut point based on swallows per minute, spontaneous SFA demonstrated superior ability to identify dysphagia cases compared with a nurse-administered clinical screening tool. In addition, spontaneous SFA demonstrated equal or superior psychometric properties to 4 validated, published clinical dysphagia screening tools. Conclusions Spontaneous SFA has high potential to identify dysphagia in acute stroke with psychometric properties equal or superior to clinical screening protocols. PMID:25088166

  19. Medicare Part D Claims Rejections for Nursing Home Residents, 2006 to 2010

    PubMed Central

    Stevenson, David G.; Keohane, Laura M.; Mitchell, Susan L.; Zarowitz, Barbara J.; Huskamp, Haiden A.

    2013-01-01

    Objectives Much has been written about trends in Medicare Part D formulary design and consumers’ choice of plans, but little is known about the magnitude of claims rejections or their clinical and administrative implications. Our objective was to study the overall rate at which Part D claims are rejected, whether these rates differ across plans, drugs, and medication classes, and how these rejection rates and reasons have evolved over time. Study Design and Methods We performed descriptive analyses of data on paid and rejected Part D claims submitted by 1 large national long-term care pharmacy from 2006 to 2010. In each of the 5 study years, data included approximately 450,000 Medicare beneficiaries living in long-term care settings with approximately 4 million Part D drug claims. Claims rejection rates and reasons for rejection are tabulated for each study year at the plan, drug, and class levels. Results Nearly 1 in 6 drug claims was rejected during the first 5 years of the Medicare Part D program, and this rate has increased over time. Rejection rates and reasons for rejection varied substantially across drug products and Part D plans. Moreover, the reasons for denials evolved over our study period. Coverage has become less of a factor in claims rejections than it was initially and other formulary tools such as drug utilization review, quantity-related coverage limits, and prior authorization are increasingly used to deny claims. Conclusions Examining claims rejection rates can provide important supplemental information to assess plans’ generosity of coverage and to identify potential areas of concern. PMID:23145808

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

    PubMed

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

    2013-11-01

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

  1. [Clinical features and management of acute myositis in idiopathic orbital inflammation].

    PubMed

    Halimi, E; Rosenberg, R; Wavreille, O; Bouckehove, S; Franquet, N; Labalette, P

    2013-09-01

    Acute myositis is the second most common component of non-specific orbital inflammation. We will describe its clinical features and natural history. This is a retrospective study of 10 cases. The diagnosis of acute myositis was based on clinical and imaging criteria. Our study includes five men and five women. The average age was 35.8 years (17-59 years). Clinical symptoms were: pain increased on eye movement (10/10), diplopia (4/10), proptosis (6/10), visual loss (3/10), lid edema (6/10), conjunctival hyperemia (7/10), anterior scleritis (2/10), episcleritis (2/10), chemosis (4/10), upper lid retraction (1/10), limitation of eye movement (3/10), fundus abnormalities (2/10). Imaging showed thickening of one or more extraocular muscles (10/10). Recovery was complete with anti-inflammatory therapy in six patients. Three patients experienced recurrence, and one patient had a clinical rebound upon tapering the treatment. Acute myositis can be defined by pain on eye movement, signs of inflammation, and extraocular muscle thickening on imaging. If the clinical presentation is typical, histopathological analysis can be deferred but remains necessary in cases of poor response to treatment, chronic duration or suspicion of tumor infiltration. The diagnosis of acute myositis may be suspected in the presence of consistent, well-defined clinical signs. Contiguous inflammation is often associated. Treatment is based on steroids or non-steroidal treatment anti-inflammatory therapy, administered alone or consecutively. Recurrences are frequent but do not alter the final prognosis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  2. Occurrence of Clinical and Sub-Clinical Mastitis in Dairy Herds in the West Littoral Region in Uruguay

    PubMed Central

    Gianneechini, R; Concha, C; Rivero, R; Delucci, I; López, J Moreno

    2002-01-01

    Twenty-nine dairy farms were selected to determine the incidence of clinical mastitis, prevalence of sub-clinical mastitis and bacterial aetiology in the West Littoral Region of Uruguay. In samples taken by the owner and frozen at -20°C during a week the incidence rate of clinical mastitis was determined as 1.2 cases per 100 cow-months at risk. Staphylococcus aureus was the most common isolated pathogen in 37.5% of 40 milk samples from clinical cases obtained in 1 month. No bacteria grew in the 32.5% of the total samples. A sub-sample including 1077 dairy cows from randomly selected farms was used to determine the prevalence of sub-clinical mastitis. These samples were taken on one visit to each farm. The prevalence was 52.4% on a cow basis and 26.7% on an udder quarter basis. In 55.1% of the quarters of the selected animals with more than 300 000 cells/ml there was no growth. The isolated pathogens from sub-clinical cases and their relative frequencies were: Staphylococcus aureus 62.8%, Streptococcus agalactiae 11.3%, Enterococcus sp. 8%, coagulase-negative staphylococci 7.4%, Streptococus uberis 6.4%, Streptococcus dysgalactiae 1.8%, Escherichia coli 1.5% and Staphylococcus hyicus coagulase-positive 0.6%. PMID:12831175

  3. Kinematic measures for upper limb motor assessment during robot-mediated training in patients with severe sub-acute stroke.

    PubMed

    Duret, Christophe; Courtial, Ophélie; Grosmaire, Anne Gaelle

    2016-01-01

    Kinematic assessments are increasingly used as motor outcome measures during upper limb robot-assisted training, in addition to clinical scales. However, their relevance has not been evaluated much. Thirty-eight patients with severe sub-acute stroke (age 56 ± 17 [19-87] years; time since stroke, 55 ± 22 days) carried out 16 sessions (average 3/week, 35 ± 15 days) of upper limb robot-assisted training combined with standard therapy. Pre/post motor performance was evaluated using the Fugl-Meyer Assessment scale, Motor Status Scale (MSS) and kinematic measures. Motor outcomes were compared and relationships between clinical and kinematic outcomes were analyzed. All clinical and kinematic outcomes improved after training (p <  0.01). FM score increased from 17.7 ± 10.0 to 28.6 ± 15.4. All baseline kinematic measures were strongly correlated with clinical scores. Correlations between clinical and kinematic changes were moderate (r = -0.65 for change in FM Proximal score and change in accuracy measure). However, smoothness and accuracy indicators were shown to be responsive measures. This study demonstrated that baseline kinematic measures and their pre/post training changes were significantly correlated with clinical motor outcome measures. However, even if kinematic measures are valid for the evaluation of motor impairment we cannot propose to substitute common clinical measures of motor function which also evaluate functional abilities of the upper limb.

  4. [Acute lithium poisoning: epidemiology, clinical characteristics, and treatment].

    PubMed

    Burguera Vion, Víctor; Montes, José Manuel; Del Rey, José Manuel; Rivera-Gorrín, Maite; Rodao, José María; Tenorio, Maite; Saiz-Ruiz, Jerónimo; Liaño, Fernando

    2017-02-01

    Lithium continues to be the treatment of choice for bipolar disorder. Acute lithium poisoning is a potentially serious event. We present a retrospective observational significative study of episodes of acute lithium poisoning during a 52- month period. Poisoning was defined by a blood lithium concentration of 1.5 mEq/L or higher. We analyzed treatment and epidemiologic and clinical characteristics of 70 episodes were identified (incidence density among treated patients, 1.76 per 100 patient-years). The most frequent cause of lithium poisoning was a concurrent medical condition (46%). Most poisonings were mild (74.2%), but neurologic involvement was identified in 40.3%. Electrocardiographic abnormalities were found in 8 cases. Acute renal failure, found in 23 patients (37.1%), was mild in most cases, although 11 patients required hemodialysis. We concluded that acute lithium poisoning is an uncommon complication, but risk needs to be lowered. Patients should be warned to avoid dosage errors and to take special care during concurrent illnesses and while taking other medications.

  5. Counter-regulation of rejection activity against human liver grafts by donor PD-L1 and recipient PD-1 interaction.

    PubMed

    Shi, Xiao-Lei; Mancham, Shanta; Hansen, Bettina E; de Knegt, Robert J; de Jonge, Jeroen; van der Laan, Luc J W; Rivadeneira, Fernando; Metselaar, Herold J; Kwekkeboom, Jaap

    2016-06-01

    Co-inhibitory receptor-ligand interactions fine-tune immune responses by negatively regulating T cell functions. Our aim is to examine the involvement of co-inhibitory receptor-ligand pair PD-1/PD-L1 in regulating rejection after liver transplantation (LT) in humans. PD-L1/PD-1 expression in liver allograft was determined by immunohistochemistry or flow cytometry, and the effect of blockade was studied using graft-infiltrating T cells ex vivo. Five single nucleotide polymorphisms within PD-1 and PD-L1 genes were genotyped in 528 LT recipients and 410 donors, and associations with both early (⩽6months) and late (>6months) acute rejection were analyzed using Cox proportional-hazards regression model. The effect of PD-L1 rs4143815 on PD-L1 expression was analyzed using donor hepatic leukocytes. PD-L1 was expressed by hepatocytes, cholangiocytes and along the sinusoids in post-transplant liver allografts, and PD-1 was abundantly expressed on allograft-infiltrating T cells. PD-L1 blockade enhanced allogeneic proliferative responses of graft-infiltrating T cells. In the genetic association analysis, donor PD-L1 rs4143815 (CC/CG vs. GG; HR=0.230; p=0.002) and recipient PD-1 rs11568821 (AA/AG vs. GG; HR=3.739; p=0.004) were associated with acute rejection late after LT in multivariate analysis. Recipients carrying the PD-1 rs11568821 A allele who were transplanted with liver grafts of PD-L1 rs4143815 GG homozygous donors showed the highest risk for late acute rejection. PD-L1 rs4143815 is associated with differential PD-L1 expression on donor hepatic dendritic cells upon IFN-γ stimulation. Our data suggest that interplay between donor PD-L1 and recipient PD-1 counter-regulates rejection activity against liver grafts in humans. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  6. Cost-effectiveness of manual therapy versus physiotherapy in patients with sub-acute and chronic neck pain: a randomised controlled trial.

    PubMed

    van Dongen, J M; Groeneweg, R; Rubinstein, S M; Bosmans, J E; Oostendorp, R A B; Ostelo, R W J G; van Tulder, M W

    2016-07-01

    To evaluate the cost-effectiveness of manual therapy according to the Utrecht School (MTU) in comparison with physiotherapy (PT) in sub-acute and chronic non-specific neck pain patients from a societal perspective. An economic evaluation was conducted alongside a 52-week randomized controlled trial, in which 90 patients were randomized to the MTU group and 91 to the PT group. Clinical outcomes included perceived recovery (yes/no), functional status (continuous and yes/no), and quality-adjusted life-years (QALYs). Costs were measured from a societal perspective using self-reported questionnaires. Missing data were imputed using multiple imputation. To estimate statistical uncertainty, bootstrapping techniques were used. After 52 weeks, there were no significant between-group differences in clinical outcomes. During follow-up, intervention costs (β:€-32; 95 %CI: -54 to -10) and healthcare costs (β:€-126; 95 %CI: -235 to -32) were significantly lower in the MTU group than in the PT group, whereas unpaid productivity costs were significantly higher (β:€186; 95 %CI:19-557). Societal costs did not significantly differ between groups (β:€-96; 95 %CI:-1975-2022). For QALYs and functional status (yes/no), the maximum probability of MTU being cost-effective in comparison with PT was low (≤0.54). For perceived recovery (yes/no) and functional status (continuous), a large amount of money must be paid per additional unit of effect to reach a reasonable probability of cost-effectiveness. From a societal perspective, MTU was not cost-effective in comparison with PT in patients with sub-acute and chronic non-specific neck pain for perceived recovery, functional status, and QALYs. As no clear total societal cost and effect differences were found between MTU and PT, the decision about what intervention to administer, reimburse, and/or implement can be based on the preferences of the patient and the decision-maker at hand. ClinicalTrials.gov Identifier: NCT00713843.

  7. Why do people reject unintended inequity? Responders' rejection in a truncated ultimatum game.

    PubMed

    Ohmura, Yu; Yamagishi, Toshio

    2005-04-01

    Rejection of an inequitable and yet unintended outcome in a truncated ultimatum game was examined in an experiment with 46 undergraduate students (27 men and 19 women) from a large national university in Japan. In an ultimatum game, one of two players, the proposer, makes an offer to divide a fixed-sum of money. The other player, the responder, decides whether to accept or reject the offer. When the responder rejects the proposer's offer, neither of the two players receives a reward. Previous work examining the behavior of participants in the truncated ultimatum game employed strategy method in their experimental design. We examined whether these previous findings would be replicated in an experimental design that did not use the strategy method and instead used the standard one-shot game. Seven out of 46 responders given an inequitable offer rejected it, replicating prior results with the strategy method. We further found that subjects who rejected an offer that was involuntary and yet inequitable did not over-attribute intentions to the proposer's involuntary behavior more strongly than did acceptors. These findings strongly suggest that aversion to inequity is the explanation for the subjects' rejection of the inequitable offer.

  8. 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.

  9. Clinical and microbiological characteristics of spontaneous acute prostatitis and transrectal prostate biopsy-related acute prostatitis: Is transrectal prostate biopsy-related acute prostatitis a distinct acute prostatitis category?

    PubMed

    Kim, Jong Wook; Oh, Mi Mi; Bae, Jae Hyun; Kang, Seok Ho; Park, Hong Seok; Moon, Du Geon

    2015-06-01

    This study aimed to compare the clinical and microbiological characteristics between acute bacterial prostatitis and transrectal biopsy-related acute prostatitis. We retrospectively reviewed the records of 135 patients hospitalized for acute prostatitis in three urological centers between 2004 and 2013. Acute bacterial prostatitis was diagnosed according to typical symptoms, findings of physical examination, and laboratory test results. Clinical variables, laboratory test results, and anti-microbial susceptibility results were reviewed. Patients were classified into the spontaneous acute prostatitis group (S-ABP) or biopsy-related acute prostatitis (Bx-ABP) for comparison of their clinical, laboratory, and microbiological findings. The mean age of all patients was 61.7 ± 12.9 years. Compared with S-ABP patients, Bx-ABP patients were significantly older, had larger prostate volumes, higher PSA values, higher peak fever temperatures, and higher incidence of septicemia and antibiotic-resistant bacteria. Overall, of the 135 patients, 57.8% had positive bacterial urine and/or blood cultures. Bx-ABP patients had a higher incidence of bacterial (urine and/or blood) positive cultures compared to S-ABP patients (66.7% versus 55.6%). Escherichia coli was the predominant organism in both groups, but it was more common in Bx-ABP (88.9%) than in S-ABP (66.7%). Extended spectrum beta-lactamase -producing bacteria accounted for 64.7% of culture-positive patients in the Bx-ABP group compared to 13.3% in the S-ABP group. Bx-ABP patients showed a higher incidence of septicemia and antibiotic-resistant bacteria than S-ABP patients. These results have important implications for the management and antimicrobial treatment of Bx-ABP, which may well deserve to be considered a distinct prostatitis category. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. Abbreviated AUC monitoring of cyclosporine more adequately identified patients at risk for acute rejection during induction of immunosuppressive therapy after kidney transplantation than recommended C2 concentration values.

    PubMed

    Troncoso, P; Ortiz, A M; Jara, A; Vilches, S

    2009-01-01

    Monitoring of cyclosporine (CsA) is critical during the induction of immunosuppressive therapy. Although most centers have incorporated C2 levels, our unit still uses an abbreviated AUC model which includes concentrations at C1, C2, and C6 post-dose (AUC(1-6)). The objective of this study was to compare both strategies of CsA monitoring during the first 30 days after kidney transplantation. The study included 89 recipients induced with CsA microemulsion and steroids. AUC(1-6) profiles were performed around days 3, 10, and 30 after transplantation with a target of 5500 to 6000 ng*h/mL considered therapeutic. For comparison purposes, a value of C2 >/= 1500 ng/mL was also considered therapeutic. Mean C2 and AUC(1-6) values were low dated with biopsy-proven acute rejection episodes (BPAR) during the study period. Twenty patients received living donor kidneys and overall there were 46 females. During this period, 253 AUC(1-6) were performed including 44 (17.4%) below the therapeutic range. When the analysis included only C2, 171 (67.6%) were below the therapeutic target (P < .001). Five patients experience BPAR and only AUC(1-6) at day 10 discriminated rejectors versus nonrejectors (5645 +/- 1390 and 8221 +/- 2502, respectively; P = .008). C2 was not significantly different at any time in either group. In this study, abbreviated AUC monitoring more adequately identified patients at risk for acute rejection than C2. Recommended C2 concentration levels need to be redefined in our patients.

  11. Rejected applications

    PubMed Central

    2014-01-01

    Objective: To review membership application materials (especially rejected applications) to the American Academy of Neurology (AAN) during its formative years (1947–1953). Methods: Detailed study of materials in the AAN Historical Collection. Results: The author identified 73 rejected applications. Rejected applicants (71 male, 2 female) lived in 25 states. The largest number was for the Associate membership category (49). These were individuals “in related fields who have made and are making contributions to the field of neurology.” By contrast, few applicants to Active membership or Fellowship status were rejected. The largest numbers of rejectees were neuropsychiatrists (19), neurosurgeons (16), and psychiatrists (14). Conclusion: The AAN, established in the late 1940s, was a small and politically vulnerable organization. A defining feature of the fledgling society was its inclusiveness; its membership was less restrictive than that of the older American Neurological Association. At the same time, the society needed to preserve its core as a neurologic society rather than one of psychiatry or neurosurgery. Hence, the balance between inclusiveness and exclusive identity was a difficult one to maintain. The Associate membership category, more than any other, was at the heart of this issue of self-definition. Associate members were largely practitioners of psychiatry or neurosurgery. Their membership was a source of consternation and was to be carefully been held in check during these critical formative years. PMID:24944256

  12. Understanding Rejection between First-and-Second-Grade Elementary Students through Reasons Expressed by Rejecters.

    PubMed

    García Bacete, Francisco J; Carrero Planes, Virginia E; Marande Perrin, Ghislaine; Musitu Ochoa, Gonzalo

    2017-01-01

    Objective: The aim of this research was to obtain the views of young children regarding their reasons for rejecting a peer. Method: To achieve this goal, we conducted a qualitative study in the context of theory building research using an analysis methodology based on Grounded Theory. The collected information was extracted through semi-structured individual interviews from a sample of 853 children aged 6 from 13 urban public schools in Spain. Results: The children provided 3,009 rejection nominations and 2,934 reasons for disliking the rejected peers. Seven reason categories emerged from the analysis. Four categories refer to behaviors of the rejected children that have a cost for individual peers or peer group such as: direct aggression, disturbance of wellbeing, problematic social and school behaviors and dominance behaviors. A further two categories refer to the identities arising from the preferences and choices of rejected and rejecter children and their peers: personal identity expressed through preferences and disliking, and social identity expressed through outgroup prejudices. The "no-behavior or no-choice" reasons were covered by one category, unfamiliarity. In addition, three context categories were found indicating the participants (interpersonal-group), the impact (low-high), and the subjectivity (subjective-objective) of the reason. Conclusion: This study provides researchers and practitioners with a comprehensive taxonomy of reasons for rejection that contributes to enrich the theoretical knowledge and improve interventions for preventing and reducing peer rejection.

  13. Understanding Rejection between First-and-Second-Grade Elementary Students through Reasons Expressed by Rejecters

    PubMed Central

    García Bacete, Francisco J.; Carrero Planes, Virginia E.; Marande Perrin, Ghislaine; Musitu Ochoa, Gonzalo

    2017-01-01

    Objective: The aim of this research was to obtain the views of young children regarding their reasons for rejecting a peer. Method: To achieve this goal, we conducted a qualitative study in the context of theory building research using an analysis methodology based on Grounded Theory. The collected information was extracted through semi-structured individual interviews from a sample of 853 children aged 6 from 13 urban public schools in Spain. Results: The children provided 3,009 rejection nominations and 2,934 reasons for disliking the rejected peers. Seven reason categories emerged from the analysis. Four categories refer to behaviors of the rejected children that have a cost for individual peers or peer group such as: direct aggression, disturbance of wellbeing, problematic social and school behaviors and dominance behaviors. A further two categories refer to the identities arising from the preferences and choices of rejected and rejecter children and their peers: personal identity expressed through preferences and disliking, and social identity expressed through outgroup prejudices. The “no-behavior or no-choice” reasons were covered by one category, unfamiliarity. In addition, three context categories were found indicating the participants (interpersonal–group), the impact (low–high), and the subjectivity (subjective–objective) of the reason. Conclusion: This study provides researchers and practitioners with a comprehensive taxonomy of reasons for rejection that contributes to enrich the theoretical knowledge and improve interventions for preventing and reducing peer rejection. PMID:28421008

  14. Tc-NGA imaging in liver transplantation: preliminary clinical experience

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woodle, E.S.; Ward, R.E.; Stadalnik, R.C.

    1989-03-01

    Technetium-99m galactosyl-neoglycoalbumin (Tc-NGA) is a new liver imaging agent that binds to hepatic-binding protein, a hepatocyte-specific membrane receptor. The purpose of this study was to determine the potential of Tc-NGA imaging in clinical liver transplantation. A total of 25 studies were performed in nine patients. Imaging studies performed in the early posttransplant period in patients with good hepatic allograft function revealed diffuse patchiness in tracer distribution, a manifestation of preservation damage. Left lobar infarction was demonstrated within a few hours of ischemic injury. Right posterior segmental infarction was seen in another patient. Comparison of kinetic, clinical, and biochemical data revealedmore » good correlation between hepatic allograft function and Tc-NGA kinetics. Major kinetic alterations were noted during periods of preservation injury, hepatic infarction, and acute rejection. These studies indicate: (1) major alterations in Tc-NGA kinetics occur during preservation injury, hepatic infarction, and acute rejection, and (2) Tc-NGA kinetic data appear to provide an accurate reflection of hepatic allograft function. Tc-NGA imaging has the advantages of being noninvasive and of utilizing standard nuclear medicine instrumentation, including portable imaging devices. In conclusion, Tc-NGA imaging provides a promising noninvasive approach for evaluation of liver function in patients undergoing hepatic transplantation.« less

  15. Spontaneous swallow frequency compared with clinical screening in the identification of dysphagia in acute stroke.

    PubMed

    Crary, Michael A; Carnaby, Giselle D; Sia, Isaac

    2014-09-01

    The aim of this study was to compare spontaneous swallow frequency analysis (SFA) with clinical screening protocols for identification of dysphagia in acute stroke. In all, 62 patients with acute stroke were evaluated for spontaneous swallow frequency rates using a validated acoustic analysis technique. Independent of SFA, these same patients received a routine nurse-administered clinical dysphagia screening as part of standard stroke care. Both screening tools were compared against a validated clinical assessment of dysphagia for acute stroke. In addition, psychometric properties of SFA were compared against published, validated clinical screening protocols. Spontaneous SFA differentiates patients with versus without dysphagia after acute stroke. Using a previously identified cut point based on swallows per minute, spontaneous SFA demonstrated superior ability to identify dysphagia cases compared with a nurse-administered clinical screening tool. In addition, spontaneous SFA demonstrated equal or superior psychometric properties to 4 validated, published clinical dysphagia screening tools. Spontaneous SFA has high potential to identify dysphagia in acute stroke with psychometric properties equal or superior to clinical screening protocols. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. High frequency of central memory regulatory T cells allows detection of liver recipients at risk of early acute rejection within the first month after transplantation

    PubMed Central

    Boix-Giner, Francisco; Millan, Olga; San Segundo, David; Muñoz-Cacho, Pedro; Mancebo, Esther; Llorente, Santiago; Rafael-Valdivia, Lourdes; Rimola, Antoni; Fábrega, Emilio; Mrowiec, Anna; Allende, Luis; Minguela, Alfredo; Bolarín, Jose M.; Paz-Artal, Estela; López-Hoyos, Marcos; Brunet, Mercé

    2016-01-01

    Several studies have analyzed the potential of T regulatory cells (Treg cells) as biomarkers of acute rejection (AR). The aim of the present multicenter study was to correlate the percentage of peripheral Treg cells in liver graft recipients drawn at baseline up to 12 months after transplantation with the presence of AR. The percentage of central memory (cm) Treg cells (CD4+CD25highCD45RO+CD62L+) was monitored at pre-transplant and at 1 and 2 weeks, and 1, 2, 3 and 6 months and 1 year post-transplantation. The same validation standard operating procedures were used in all participating centers. Fifteen patients developed AR (23.4%). Hepatitis C virus recurrence was observed in 16 recipients, who displayed low peripheral blood cmTreg levels compared with patients who did not. A steady increase of cmTregs was observed during the first month after transplantation with statistically significant differences between AR and non-AR patients. The high frequency of memory Treg cells allowed us to monitor rejection episodes during the first month post-transplantation. On the basis of these data, we developed a prediction model for assessing risk of AR that can provide clinicians with useful information for managing patients individually and customizing immunosuppressive therapies. PMID:26270267

  17. [Secondary cardiovascular prevention after acute coronary syndrome in clinical practice].

    PubMed

    Colivicchi, Furio; Di Roma, Angelo; Uguccioni, Massimo; Scotti, Emilio; Ammirati, Fabrizio; Arcas, Marcello; Avallone, Aniello; Bonaccorso, Orazio; Germanò, Giuseppe; Letizia, Claudio; Manfellotto, Dario; Minardi, Giovanni; Pristipino, Christian; D'Amore, Francesco; Di Veroli, Claudio; Fierro, Aldo; Pastorellio, Ruggero; Tozzi, Quinto; Tubaro, Marco; Santini, Massimo; Angelico, Francesco; Azzolini, Paolo; Bellasi, Antonio; Brocco, Paola; Calò, Leonardo; Cerquetani, Elena; De Biase, Luciano; Di Napoli, Mauro; Galati, Alfonso; Gallieni, Maurizio; Jesi, Anna Patrizia; Lombardo, Antonella; Loricchio, Vincenzo; Menghini, Fabio; Mezzanotte, Roberto; Minutolos, Roberto; Mocini, David; Patti, Giuseppe; Patrizi, Roberto; Pajes, Giuseppe; Pulignano, Giovanni; Ricci, Renato Pietro; Ricci, Roberto; Sardella, Gennaro; Strano, Stefano; Terracina, David; Testa, Marco; Tomai, Fabrizio; Volpes, Roberto; Volterrani, Maurizio

    2010-05-01

    Secondary prevention after acute coronary syndromes should be aimed at reducing the risk of further adverse cardiovascular events, thereby improving quality of life, and lengthening survival. Despite compelling evidence from large randomized controlled trials, secondary prevention is not fully implemented in most cases after hospitalization for acute coronary syndrome. The Lazio Region (Italy) has about 5.3 million inhabitants (9% of the entire Italian population). Every year about 11 000 patients are admitted for acute coronary syndrome in hospitals of the Lazio Region. Most of these patients receive state-of-the art acute medical and interventional care during hospitalization. However, observational data suggest that after discharge acute coronary syndrome patients are neither properly followed nor receive all evidence-based treatments. This consensus document has been developed by 11 Scientific Societies of Cardiovascular and Internal Medicine in order develop a sustainable and effective clinical approach for secondary cardiovascular prevention after acute coronary syndrome in the local scenario of the Lazio Region. An evidence-based simplified decalogue for secondary cardiovascular prevention is proposed as the cornerstone of clinical intervention, taking into account regional laws and relative shortage of resources. The following appropriate interventions should be consistently applied: smoking cessation, blood pressure control (blood pressure < 130/80 mmHg), optimal lipid management (LDL cholesterol < 80 mmHg), weight and diabetes management, promotion of physical activity and rehabilitation, correct use of antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers.

  18. Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats.

    PubMed

    Yuan, Guiping; Dai, Shujun; Yin, Zhongqiong; Lu, Hongke; Jia, Renyong; Xu, Jiao; Song, Xu; Li, Li; Shu, Yang; Zhao, Xinghong

    2014-03-01

    The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD50 value of Pb(NO3)2 and CdCl2 mixture by the oral route was 2696.54mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague-Dawley (SD) rats with dose-response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96mg/(kgbwday) when administered orally for 90 consecutive days. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Multivariate prediction of upper limb prosthesis acceptance or rejection.

    PubMed

    Biddiss, Elaine A; Chau, Tom T

    2008-07-01

    To develop a model for prediction of upper limb prosthesis use or rejection. A questionnaire exploring factors in prosthesis acceptance was distributed internationally to individuals with upper limb absence through community-based support groups and rehabilitation hospitals. A total of 191 participants (59 prosthesis rejecters and 132 prosthesis wearers) were included in this study. A logistic regression model, a C5.0 decision tree, and a radial basis function neural network were developed and compared in terms of sensitivity (prediction of prosthesis rejecters), specificity (prediction of prosthesis wearers), and overall cross-validation accuracy. The logistic regression and neural network provided comparable overall accuracies of approximately 84 +/- 3%, specificity of 93%, and sensitivity of 61%. Fitting time-frame emerged as the predominant predictor. Individuals fitted within two years of birth (congenital) or six months of amputation (acquired) were 16 times more likely to continue prosthesis use. To increase rates of prosthesis acceptance, clinical directives should focus on timely, client-centred fitting strategies and the development of improved prostheses and healthcare for individuals with high-level or bilateral limb absence. Multivariate analyses are useful in determining the relative importance of the many factors involved in prosthesis acceptance and rejection.

  20. A novel measure of reliability in Diffusion Tensor Imaging after data rejections due to subject motion.

    PubMed

    Sairanen, V; Kuusela, L; Sipilä, O; Savolainen, S; Vanhatalo, S

    2017-02-15

    Diffusion Tensor Imaging (DTI) is commonly challenged by subject motion during data acquisition, which often leads to corrupted image data. Currently used procedure in DTI analysis is to correct or completely reject such data before tensor estimations, however assessing the reliability and accuracy of the estimated tensor in such situations has evaded previous studies. This work aims to define the loss of data accuracy with increasing image rejections, and to define a robust method for assessing reliability of the result at voxel level. We carried out simulations of every possible sub-scheme (N=1,073,567,387) of Jones30 gradient scheme, followed by confirming the idea with MRI data from four newborn and three adult subjects. We assessed the relative error of the most commonly used tensor estimates for DTI and tractography studies, fractional anisotropy (FA) and the major orientation vector (V1), respectively. The error was estimated using two measures, the widely used electric potential (EP) criteria as well as the rotationally variant condition number (CN). Our results show that CN and EP are comparable in situations with very few rejections, but CN becomes clearly more sensitive to depicting errors when more gradient vectors and images were rejected. The error in FA and V1 was also found depend on the actual FA level in the given voxel; low actual FA levels were related to high relative errors in the FA and V1 estimates. Finally, the results were confirmed with clinical MRI data. This showed that the errors after rejections are, indeed, inhomogeneous across brain regions. The FA and V1 errors become progressively larger when moving from the thick white matter bundles towards more superficial subcortical structures. Our findings suggest that i) CN is a useful estimator of data reliability at voxel level, and ii) DTI preprocessing with data rejections leads to major challenges when assessing brain tissue with lower FA levels, such as all newborn brain, as well as

  1. 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

  2. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in vivo bioavailability data with an acute pharmacological effect or clinical evidence of safety and...

  3. Clinical case definition for the diagnosis of acute intussusception.

    PubMed

    Bines, Julie E; Ivanoff, Bernard; Justice, Frances; Mulholland, Kim

    2004-11-01

    Because of the reported association between intussusception and a rotavirus vaccine, future clinical trials of rotavirus vaccines will need to include intussusception surveillance in the evaluation of vaccine safety. The aim of this study is to develop and validate a clinical case definition for the diagnosis of acute intussusception. A clinical case definition for the diagnosis of acute intussusception was developed by analysis of an extensive literature review that defined the clinical presentation of intussusception in 70 developed and developing countries. The clinical case definition was then assessed for sensitivity and specificity using a retrospective chart review of hospital admissions. Sensitivity of the clinical case definition was assessed in children diagnosed with intussusception over a 6.5-year period. Specificity was assessed in patients aged <2 years admitted with bowel obstruction and in patients aged <19 years presenting with symptoms that may occur in intussusception. The clinical case definition accurately identified 185 of 191 assessable cases as "probable" intussusception and six cases as "possible" intussusception (sensitivity, 97%). No case of radiologic or surgically proven intussusception failed to be identified by the clinical case definition. The specificity of the definition in correctly identifying patients who did not have intussusception ranged from 87% to 91%. The clinical case definition for intussusception may assist in the prompt identification of patients with intussusception and may provide an important tool for the future trials of enteric vaccines.

  4. Escaping from Rejection

    PubMed Central

    Lynch, Raymond J.; Platt, Jeffrey L.

    2009-01-01

    Summary Those engaged in clinical transplantation and transplantation immunology have always taken as a central objective the elucidation of means to prevent graft rejection by the recipient immune system. Conceptually, such mechanisms stem from the concept of Paul Ehrlich that all organisms can selectively avoid autotoxicity; i.e. they exhibit horror autotoxicus. Some mechanisms of horror autotoxicus now understood. T lymphocytes and B lymphocytes recognize foreign antigens but not some auto-antigens. Clonal deletion generates lacunae in what is otherwise a virtually limitless potential to recognize antigens. We call this mechanism structural tolerance. Where imperfections in structural tolerance allow self-recognition, the full activation of lymphocytes and generation of effector activity depends on delivery of accessory signals generated by infection and/or injury. The absence of accessory signals prevents or even suppresses immunological responses. We call this dichotomy of responsiveness conditional tolerance. When, despite structural and conditional tolerance, effector activity perturbs autologous cells, metabolism changes in ways that protect against injury. We use the term accommodation to refer to this acquired protection against injury. Structural and conditional tolerance and accommodation overlap in such a way that potentially toxic products can be generated to control microorganisms and neutralize toxins without overly damaging adjacent cells. The central challenge in transplantation, then, should be the orchestration of structural and conditional tolerance and accommodation in such a way that toxic products can still be generated for defense while preserving graft function and survival. Since the earliest days of transplantation, immunobiologists have sought means by which to prevent recognition and rejection of foreign tissue. The goal of these strategies is the retention of recipient immune function while selectively avoiding graft injury. While

  5. Self-limiting filters for band-selective interferer rejection or cognitive receiver protection

    DOEpatents

    Nordquist, Christopher; Scott, Sean Michael; Custer, Joyce Olsen; Leonhardt, Darin; Jordan, Tyler Scott; Rodenbeck, Christopher T.; Clem, Paul G.; Hunker, Jeff; Wolfley, Steven L.

    2017-03-07

    The present invention related to self-limiting filters, arrays of such filters, and methods thereof. In particular embodiments, the filters include a metal transition film (e.g., a VO.sub.2 film) capable of undergoing a phase transition that modifies the film's resistivity. Arrays of such filters could allow for band-selective interferer rejection, while permitting transmission of non-interferer signals.

  6. Defensive Physiological Reactions to Rejection

    PubMed Central

    Gyurak, Anett; Ayduk, Özlem

    2014-01-01

    We examined the hypothesis that rejection automatically elicits defensive physiological reactions in people with low self-esteem (SE) but that attentional control moderates this effect. Undergraduates (N = 67) completed questionnaire measures of SE and attentional control. Their eye-blink responses to startle probes were measured while they viewed paintings related to rejection and acceptance themes. The stimuli also included positive-, negative-, and neutral-valence control paintings unrelated to rejection. As predicted, compared with people high in SE, those low in SE showed stronger startle eye-blink responses to paintings related to rejection, but not to negative paintings. Paintings related to acceptance did not attenuate their physiological reactivity. Furthermore, attentional control moderated their sensitivity to rejection, such that low SE was related to greater eye-blink responses to rejection only among individuals who were low in attentional control. Implications of the role of attentional control as a top-down process regulating emotional reactivity in people with low SE are discussed. PMID:17894606

  7. 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.

  8. [Clinical course of acute poisoning with olanzapine].

    PubMed

    Balicka-Slusarczyk, Barbara; Szczeklik, Jerzy; Szpak, Dorota; Groszek, Barbara

    2005-01-01

    Olanzapine is a new atypical antipsychotic drug acting on different receptors. A variety of pharmacologic effects are responsible for toxicity and the variety of clinical symptoms seen in overdose: tachycardia, agitation or aggression, dysarthria, extrapyramidal dystonic effects, sedation or coma, small pupils, blurred vision, respiratory depression, hypotension. A retrospective analysis of clinical course of eight acute olanzapine intoxication treated at the Department of Clinical Toxicology Jagiellonian University Medical College is presented. CNS symptoms manifested in fluctuations between somnolence/coma and agitation/aggression and miosis were observed in most of the patients. Increased CPK activity was stated in the most of patients. All of the patients recovered, poisoning severity according PSS was moderate and severe.

  9. Antibody-mediated rejection of the lung: A consensus report of the International Society for Heart and Lung Transplantation.

    PubMed

    Levine, Deborah J; Glanville, Allan R; Aboyoun, Christina; Belperio, John; Benden, Christian; Berry, Gerald J; Hachem, Ramsey; Hayes, Don; Neil, Desley; Reinsmoen, Nancy L; Snyder, Laurie D; Sweet, Stuart; Tyan, Dolly; Verleden, Geert; Westall, Glen; Yusen, Roger D; Zamora, Martin; Zeevi, Adriana

    2016-04-01

    Antibody-mediated rejection (AMR) is a recognized cause of allograft dysfunction in lung transplant recipients. Unlike AMR in other solid-organ transplant recipients, there are no standardized diagnostic criteria or an agreed-upon definition. Hence, a working group was created by the International Society for Heart and Lung Transplantation with the aim of determining criteria for pulmonary AMR and establishing a definition. Diagnostic criteria and a working consensus definition were established. Key diagnostic criteria include the presence of antibodies directed toward donor human leukocyte antigens and characteristic lung histology with or without evidence of complement 4d within the graft. Exclusion of other causes of allograft dysfunction increases confidence in the diagnosis but is not essential. Pulmonary AMR may be clinical (allograft dysfunction which can be asymptomatic) or sub-clinical (normal allograft function). This consensus definition will have clinical, therapeutic and research implications. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Transient blockade of Delta-like Notch ligands prevents allograft rejection mediated by cellular and humoral mechanisms in a mouse model of heart transplantation

    PubMed Central

    Wood, Sherri; Feng, Jiane; Chung, Jooho; Radojcic, Vedran; Sandy, Ashley R.; Friedman, Ann; Shelton, Amy; Yan, Minhong; Siebel, Christian W.; Bishop, D. Keith; Maillard, Ivan

    2015-01-01

    Rejection remains a major clinical challenge limiting allograft survival after solid organ transplantation. Both cellular and humoral immunity contribute to this complication, with increased recognition of antibody-mediated damage during acute and chronic rejection. Using a mouse model of MHC-mismatched heart transplantation, we report markedly protective effects of Notch inhibition, dampening both T cell and antibody-driven rejection. T cell-specific pan-Notch blockade prolonged heart allograft survival and decreased IFNγ and IL-4 production by alloreactive T cells, especially when combined with depletion of recipient CD8+ T cells. These effects were associated with decreased infiltration by conventional T cells and an increased proportion of regulatory T cells in the graft. Transient administration of neutralizing antibodies specific for Delta-like1/4 (Dll1/4) Notch ligands in the peri-transplant period led to prolonged acceptance of allogeneic hearts, with superior outcome over Notch inhibition only in T cells. Systemic Dll1/4 inhibition decreased T cell cytokines and graft infiltration, but also germinal center B cell and plasmablast numbers as well as production of donor-specific alloantibodies and complement deposition in the transplanted hearts. Dll1 or Dll4 inhibition alone provided partial protection. Thus, pathogenic signals delivered by Dll1/4 Notch ligands early after transplantation promote organ rejection through several complementary mechanisms. Transient interruption of theses signals represents a new attractive therapeutic strategy to enhance long-term allograft survival. PMID:25687759

  11. Behavioral Response Generation and Selection of Rejected-Reactive Aggressive, Rejected-Nonaggressive, and Average Status Children.

    ERIC Educational Resources Information Center

    Wood, C. Nannette; Gross, Alan M.

    2002-01-01

    Examines response decision processes of rejected-reactive aggressive, rejected-nonaggressive and average children in terms of the presence or absence of behavioral response alternatives. Congruent with previous research, rejected-reactive aggressive children made significantly more hostile attributions and generated a higher number of aggressive…

  12. Gene-expression profiling for rejection surveillance after cardiac transplantation.

    PubMed

    Pham, Michael X; Teuteberg, Jeffrey J; Kfoury, Abdallah G; Starling, Randall C; Deng, Mario C; Cappola, Thomas P; Kao, Andrew; Anderson, Allen S; Cotts, William G; Ewald, Gregory A; Baran, David A; Bogaev, Roberta C; Elashoff, Barbara; Baron, Helen; Yee, James; Valantine, Hannah A

    2010-05-20

    Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of gene-expression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; P=0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, P<0.001). Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved gene-expression profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.) 2010 Massachusetts Medical Society

  13. In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

    PubMed

    Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

    2018-04-15

    The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

  14. History of Abuse and Risky Sex among Substance Users: The Role of Rejection Sensitivity and the Need to Belong

    PubMed Central

    Woerner, Jacqueline; Kopetz, Catalina; Lechner, William V.; Lejuez, Carl

    2016-01-01

    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 = .124, SE = .040, p = .002), which was in turn associated with increased risky sex (B = .06, SE = .028, p = .03) (indirect effect = .0075, SE = .0043; 95% CI [.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

  15. Rejection of false saturation data in optical pulse-oximeter

    NASA Astrophysics Data System (ADS)

    Scalise, Lorenzo; Marchionni, Paolo; Carnielli, Virgilio

    2010-04-01

    are not validated by the use of our method (corresponding to a total time of 16 hr, 8min and 40s). The use of the proposed algorithm aiming to "rescue" data from short sequences of rejected data (< 8s) allows to increase the validated data of the 2.5%t(equivalent to 8hr, 40 min and 16s), allowing a percent of usable data of the 95.7%. Once implemented in clinic, it could be used to identify the period of the day in which the percent of rejected data increase or correlate this data to clinical procedure in order to intensify clinicians and nurses attention.

  16. Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

    PubMed Central

    Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients’ dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail. PMID:26858719

  17. Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation.

    PubMed

    Thomson, Angus W; Zahorchak, Alan F; Ezzelarab, Mohamed B; Butterfield, Lisa H; Lakkis, Fadi G; Metes, Diana M

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients' dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.

  18. National data elements for the clinical management of acute coronary syndromes.

    PubMed

    Chew, Derek P B; Allan, Roger M; Aroney, Constantine N; Sheerin, Noella J

    2005-05-02

    Patients with acute coronary syndromes represent a clinically diverse group and their care remains heterogeneous. These patients account for a significant burden of morbidity and mortality in Australia. Optimal patient outcomes depend on rapid diagnosis, accurate risk stratification and the effective implementation of proven therapies, as advocated by clinical guidelines. The challenge is in effectively applying evidence in clinical practice. Objectivity and standardised quantification of clinical practice are essential in understanding the evidence-practice gap. Observational registries are key to understanding the link between evidence-based medicine, clinical practice and patient outcome. Data elements for monitoring clinical management of patients with acute coronary syndromes have been adapted from internationally accepted definitions and incorporated into the National Health Data Dictionary, the national standard for health data definitions in Australia. Widespread use of these data elements will assist in the local development of "quality-of-care" initiatives and performance indicators, facilitate collaboration in cardiovascular outcomes research, and aid in the development of electronic data collection methods.

  19. Immunological and inflammatory mapping of vascularized composite allograft rejection processes in a rat model

    PubMed Central

    Friedman, Or; Carmel, Narin; Sela, Meirav; Abu Jabal, Ameen; Inbal, Amir; Ben Hamou, Moshe; Krelin, Yakov; Gur, Eyal

    2017-01-01

    Background Hand and face vascularized composite allotransplantation (VCA) is an evolving and challenging field with great opportunities. During VCA, massive surgical damage is inflicted on both donor and recipient tissues, which may contribute to the high VCA rejection rates. To segregate between the damage-induced and rejection phase of post-VCA responses, we compared responses occurring up to 5 days following syngeneic versus allogeneic vascularized groin flap transplantations, culminating in transplant acceptance or rejection, respectively. Methods The immune response elicited upon transplantation of a syngeneic versus allogeneic vascularized groin flap was compared at Post-operative days 2 or 5 by histology, immunohistochemistry and by broad-scope gene and protein analyses using quantitative real-time PCR and Multiplex respectively. Results Immune cell infiltration began at the donor-recipient interface and paralleled expression of a large group of wound healing-associated genes in both allografts and syngrafts. By day 5 post-transplantation, cell infiltration spread over the entire allograft but remained confined to the wound site in the syngraft. This shift correlated with upregulation of IL-18, INFg, CXCL9, 10 and 11, CCL2, CCL5, CX3CL1 and IL-10 in the allograft only, suggesting their role in the induction of the anti-alloantigen adaptive immune response. Conclusions High resemblance between the cues governing VCA and solid organ rejection was observed. Despite this high resemblance we describe also, for the first time, a damage induced inflammatory component in VCA rejection as immune cell infiltration into the graft initiated at the surgical damage site spreading to the entire allograft only at late stage rejection. We speculate that the highly inflammatory setting created by the unique surgical damage during VCA may enhance acute allograft rejection. PMID:28746417

  20. 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.

  1. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A.

    PubMed

    Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

    2015-01-01

    Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, P < 0.001), initial lactate dehydrogenase (LDH) (HR = 1.000, P = 0.045) and total cholesterol (HR = 0.978, P < 0.001) were independent factors for s-AH. Serum HAV RNA was detected in 20/20 (100%) patients with s-AH and 22/28 (78.6%) patients with m-AH. In a multivariate analysis of the 48 patients who were tested for HAV RNA, peak ALT (HR = 1.001, P = 0.004) and HAV RNA titer (HR = 2.076, P = 0.012) were independent factors for s-AH. Clinical factors including age, peak creatinine, bilirubin, ALT, initial LDH and total cholesterol were independent factors for s-AH in a multivariate analysis. In particular, HAV load strongly correlated with the severity of hepatitis A.

  2. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A

    PubMed Central

    Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

    2015-01-01

    Background and Aims Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). Methods We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. Results In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, P<0.001), initial lactate dehydrogenase (LDH) (HR = 1.000, P = 0.045) and total cholesterol (HR = 0.978, P<0.001) were independent factors for s-AH. Serum HAV RNA was detected in 20/20 (100%) patients with s-AH and 22/28 (78.6%) patients with m-AH. In a multivariate analysis of the 48 patients who were tested for HAV RNA, peak ALT (HR = 1.001, P = 0.004) and HAV RNA titer (HR = 2.076, P = 0.012) were independent factors for s-AH. Conclusions Clinical factors including age, peak creatinine, bilirubin, ALT, initial LDH and total cholesterol were independent factors for s-AH in a multivariate analysis. In particular, HAV load strongly correlated with the severity of hepatitis A. PMID:26090677

  3. Triple therapy in cadaveric renal transplantation: role of induction cyclosporine and targeted levels to avoid rejection.

    PubMed

    Khauli, R B; Wilson, J M; Baker, S P; Valliere, S A; Lovewell, T D; Stoff, J S

    1995-06-01

    The updated data on 61 consecutive cadaveric transplants performed at our institution from 1987 to 1990 (followup 31 to 82 months, median 54 months) were analyzed with emphasis on cyclosporine monitoring and long-term results. All patients received triple therapy with cyclosporine induction, azathioprine and prednisone regardless of graft function, and they were preferentially placed on the calcium blocker nifedipine. We monitored 12-hour cyclosporine trough levels in whole blood using high performance liquid chromatography and the dose was adjusted to maintain levels at 150 ng./ml. or greater for the first 3 months. In 17 of 61 patients (28%) 22 rejection episodes occurred and 20 nephrotoxicity episodes occurred in 17 of 61 patients (28%). There was no significant difference in the mean cyclosporine levels among 32 rejection, nonrejection, nephrotoxic and nonnephrotoxic cases at any interval. Rejection occurred by 1 month in 13 (76%) and by 3 months in 15 (88%) of 17 patients. Comparisons were made in the first month to define the desirable cyclosporine levels by calculating the mean cyclosporine only within 10 to 14 days of rejection or nephrotoxicity events. The mean cyclosporine level before rejection was significantly lower than that for nephrotoxicity (188 +/- 113 versus 304 +/- 62 ng./ml., p < 0.01). The median cyclosporine level for first month rejection was also significantly lower than that for nonrejection (156 versus 218 ng./ml., p < 0.05) and it was significantly greater for nephrotoxicity versus nonnephrotoxicity (272 versus 218 ng./ml., p < 0.05). Of 13 rejections in the first month 10 (77%) were associated with mean levels of less than 210 ng./ml. Actuarial graft survival at 1, 3 and 5 years was 93.4%, 87.8% and 78.5%, respectively. The 3-year graft survival was significantly worse for patients who experienced acute rejection episodes versus those who did not (68.8% versus 96.7%, p < 0.05) but it was not different for nephrotoxic versus

  4. Rejected by peers-attracted to antisocial media content: rejection-based anger impairs moral judgment among adolescents.

    PubMed

    Plaisier, Xanthe S; Konijn, Elly A

    2013-06-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents to select antisocial media content by tying together developmental research on peer rejection and research on media effects. Assumed underlying mechanisms are rejection-based anger and frustration and the adolescent's moral judgment. A between-participants experimental design manipulated peer rejection versus acceptance in adolescents (Mage = 13.88 years; N = 74) and young adults (Mage = 21.37 years; N = 75), applying the Cyberball paradigm. Measures included the State Anger Inventory (STAXI) to assess feelings of rejection and the newly devised Media, Morals, and Youth Questionnaire (MMaYQue) to assess media preferences and moral judgment of media content. Using bootstrapping analyses, a double mediation was established: Higher levels of state anger in peer-rejected adolescents induced more tolerable moral judgments of antisocial media content, subsequently instigating a preference for antisocial media content. In contrast, the young adult sample showed no relations between peer rejection and antisocial media preference. Results are discussed within a downward spiral framework of combined peer and media influences. PsycINFO Database Record (c) 2013 APA, all rights reserved

  5. [Sequential monitoring of renal transplant with aspiration cytology].

    PubMed

    Manfro, R C; Gonçalves, L F; de Moura, L A

    1998-01-01

    To evaluate the utility of kidney aspiration cytology in the sequential monitorization of acute rejection in renal transplant patients. Thirty patients were submitted to 376 aspirations. The clinical diagnoses were independently established. The representativity of the samples reached 82.7%. The total corrected increment index and the number of immunoactivated cells were higher during acute rejection as compared to normal allograft function, acute tubular necrosis, and cyclosporine nephrotoxicity. The parameters to the diagnosis of acute rejection were sensitivity: 71.8%, specificity: 87.3%, positive predictive value: 50.9%, negative predictive value: 94.9% and accuracy 84.9%. The false positive results were mainly related to cytomegalovirus infection or to the administration of OKT3. In 10 out of 11 false negative results incipient immunoactivation was present alerting to the possibility of acute rejection. Kidney aspiration cytology is a useful tool for the sequential monitorization of acute rejection in renal transplant patients. The best results are reached when the results of aspiration cytology are analyzed with the clinical data.

  6. The 'fine line' of heat rejection.

    PubMed

    Carruthers, Phillip

    2010-09-01

    Selection of heat rejection equipment has traditionally entailed a choice between the higher energy consumption of an air-cooled solution, and the high water consumption of a water-cooled solution. This paper examines advancement in heat rejection technology and the way it can be applied to air conditioning and refrigeration plant in healthcare and other facilities. It also examines field difficulties encountered in pipework design as the knowledge and experience levels of engineers designing systems with remote condensers diminish. With plant larger than 1,000 kW, the only option previously has been water-cooled solutions using an array of cooling towers, or perhaps an evaporative condenser, since air-cooled plant involved massive volumes of chemical refrigerant, which posed a problem ecologically. An additional hurdle was problems associated with limitations on pipe lengths for refrigeration plant. The advent of adiabatically pre-cooled closed circuit coolers and air-cooled condensers has introduced an alternative to cooling towers that offers the potential for "water-cooled performance" from an air-cooled solution with no serious threat of Legionella contamination. However, each application needs to be considered on a case-by-case basis. The paper examines, in detail, the impact of adiabatic pre-cooling, with recent examples of its application in sub-tropical Brisbane providing evidence of the potential performance achievable.

  7. Gene-Based Multiclass Cancer Diagnosis with Class-Selective Rejections

    PubMed Central

    Jrad, Nisrine; Grall-Maës, Edith; Beauseroy, Pierre

    2009-01-01

    Supervised learning of microarray data is receiving much attention in recent years. Multiclass cancer diagnosis, based on selected gene profiles, are used as adjunct of clinical diagnosis. However, supervised diagnosis may hinder patient care, add expense or confound a result. To avoid this misleading, a multiclass cancer diagnosis with class-selective rejection is proposed. It rejects some patients from one, some, or all classes in order to ensure a higher reliability while reducing time and expense costs. Moreover, this classifier takes into account asymmetric penalties dependant on each class and on each wrong or partially correct decision. It is based on ν-1-SVM coupled with its regularization path and minimizes a general loss function defined in the class-selective rejection scheme. The state of art multiclass algorithms can be considered as a particular case of the proposed algorithm where the number of decisions is given by the classes and the loss function is defined by the Bayesian risk. Two experiments are carried out in the Bayesian and the class selective rejection frameworks. Five genes selected datasets are used to assess the performance of the proposed method. Results are discussed and accuracies are compared with those computed by the Naive Bayes, Nearest Neighbor, Linear Perceptron, Multilayer Perceptron, and Support Vector Machines classifiers. PMID:19584932

  8. Individual differences in the rejection-aggression link in the hot sauce paradigm: The case of Rejection Sensitivity

    PubMed Central

    Ayduk, Özlem; Gyurak, Anett; Luerssen, Anna

    2008-01-01

    Prior research shows that social rejection elicits aggression. In this study, we investigated whether this is moderated by individual differences in Rejection Sensitivity (RS) – a processing disposition to anxiously expect, readily perceive and overreact to rejection. Participants (N = 129) took part in a purported web-based social interaction in which they were either rejected or not by a potential partner. Subsequently, they were given the opportunity to allocate hot sauce to the perpetrator, knowing that he/she disliked spicy food. Amount of hot sauce was used as a behavioral index of aggression. Participants in the rejection condition allocated more hot sauce to the perpetrator than those in the control condition. However, RS moderated this effect such that rejection elicited aggression in high but not in low RS people. These results held after controlling for trait neuroticism. Implications of these findings for understanding how and why rejection elicits aggression are discussed. PMID:20228947

  9. Neural mechanisms of the rejection-aggression link.

    PubMed

    Chester, David S; Lynam, Donald R; Milich, Richard; DeWall, C Nathan

    2018-05-01

    Social rejection is a painful event that often increases aggression. However, the neural mechanisms of this rejection-aggression link remain unclear. A potential clue may be that rejected people often recruit the ventrolateral prefrontal cortex's (VLPFC) self-regulatory processes to manage the pain of rejection. Using functional MRI, we replicated previous links between rejection and activity in the brain's mentalizing network, social pain network and VLPFC. VLPFC recruitment during rejection was associated with greater activity in the brain's reward network (i.e. the ventral striatum) when individuals were given an opportunity to retaliate. This retaliation-related striatal response was associated with greater levels of retaliatory aggression. Dispositionally aggressive individuals exhibited less functional connectivity between the ventral striatum and the right VLPFC during aggression. This connectivity exerted a suppressing effect on dispositionally aggressive individuals' greater aggressive responses to rejection. These results help explain how the pain of rejection and reward of revenge motivate rejected people to behave aggressively.

  10. Assessing sub-clinical psychosis phenotypes in the general population--a multidimensional approach.

    PubMed

    Rössler, Wulf; Ajdacic-Gross, Vladeta; Müller, Mario; Rodgers, Stephanie; Haker, Helene; Hengartner, Michael P

    2015-02-01

    Several studies have demonstrated that expression of a psychosis phenotype can be observed below the threshold of its clinical detection. To date, however, no conceptual certainty has been reported for the validity and reliability of sub-clinical psychosis. Our main objectives were to assess the prevalence rates and severity of various psychosis symptoms in a representative community sample. Furthermore, we wanted to analyze which latent factors are depicted by several currently used psychosis questionnaires. We also examined how those latent factors for sub-clinical psychosis are linked to psychosocial factors, normal personality traits, and coping abilities related to chronic stress. Most of the eight subscales from the Paranoia Checklist and the Structured Interview for Assessing Perceptual Anomalies had a very similar type of distribution, i.e., an inverse Gaussian (Wald) distribution. This supported the notion of a continuity of psychotic symptoms, which we would expect to find for continuously distributed symptoms within the general population. Sub-clinical psychosis can be reduced to two different factors - one representing odd beliefs about the world and odd behavior, and the other one representing anomalous perceptions (such as hallucinations). Persons with odd beliefs and behavior are under greater burden and more susceptible to psychosocial risks than are persons with anomalous perceptions. These sub-clinical psychosis syndromes are also related to stable personality traits. In conclusion, we obtained strong support for the notion that there is no natural cut-off separating psychotic illness from good health. Sub-clinical psychosis of any kind is not trivial because it is associated with various types of social disability. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Acute, 28days sub acute and genotoxic profiling of Quercetin-Magnesium complex in Swiss albino mice.

    PubMed

    Ghosh, Nilanjan; Sandur, Rajendra; Ghosh, Deepanwita; Roy, Souvik; Janadri, Suresh

    2017-02-01

    Quercetin-Magnesium complex is one of the youngest alkaline rare earth metal (Magnesium) complexes with flavonoids (Quercetin) in organo-metalic family. Earlier studies describe the details of the complex formation, characterization and antioxidant study of the complex but toxicity profile is still under darkness. The present study was taken up to investigate the oral acute toxicity, 28days repeated oral sub-acute toxicity study and genotoxicity study of Quercetin-Magnesium complex in Swiss albino mice. Quercetin-Magnesium complex showed mortality at a dose of 185mg/kg in the Swiss albino mice. In 28days repeated oral toxicity study, Quercetin-Magnesium complex was administered to both sex of Swiss albino mice at dose levels of 150, 130 and 100mg/kg body weight respectively. Where 150mg/kg dose shows increased levels of white blood cells and changes in total protein, serum creatinine and blood urea nitrogen. Histopathological study of Quercetin-Magnesium complex shows minor structural alteration in kidney at 150mg/kg dose. No observed toxic level found in 130mg/kg or below doses. No genotoxic effect found in any doses of the complex. Therefore 130mg/kg or below dose level could be better for further study. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Acute Chagas outbreaks: molecular and biological features of Trypanosoma cruzi isolates, and clinical aspects of acute cases in Santander, Colombia.

    PubMed

    Díaz, Martha Lucía; Leal, Sandra; Mantilla, Julio César; Molina-Berríos, Alfredo; López-Muñoz, Rodrigo; Solari, Aldo; Escobar, Patricia; González Rugeles, Clara Isabel

    2015-11-26

    Outbreaks of acute Chagas disease associated with oral transmission are easily detected nowadays with trained health personnel in areas of low endemicity, or in which the vector transmission has been interrupted. Given the biological and genetic diversity of Trypanosoma cruzi, the high morbidity, mortality, and the observed therapeutic failure, new characteristics of these outbreaks need to be addressed at different levels, both in Trypanosoma cruzi as in patient response. The aim of this work was to evaluate the patient's features involved in six outbreaks of acute Chagas disease which occurred in Santander, Colombia, and the characteristics of Trypanosoma cruzi clones isolated from these patients, to establish the potential relationship between the etiologic agent features with host behavior. The clinical, pathological and epidemiological aspects of outbreaks were analyzed. In addition, Trypanosoma cruzi clones were biologically characterized both in vitro and in vivo, and the susceptibility to the classical trypanocidal drugs nifurtimox and benznidazole was evaluated. Trypanosoma cruzi clones were genotyped by means of mini-exon intergenic spacer and cytochrome b genes sequencing. All clones were DTU I, and based on the mini-exon intergenic spacer, belong to two genotypes: G2 related with sub-urban, and G11 with rural outbreaks. Girón outbreak clones with higher susceptibility to drugs presented G2 genotype and C/T transition in Cyt b. The outbreaks affected mainly young population (±25.9 years), and the mortality rate was 10 %. The cardiac tissue showed intense inflammatory infiltrate, myocardial necrosis and abundant amastigote nests. However, although the gastrointestinal tissue was congestive, no inflammation or parasites were observed. Although all clones belong to DTU I, two intra-DTU genotypes were found with the sequencing of the mini-exon intergenic spacer, however there is no strict correlation between genetic groups, the cycles of the parasite or

  13. [The role of psychologist in clinic of acute poisonings].

    PubMed

    Marczyńska-Wdówik, Agnieszka M

    2009-01-01

    This paper is a kind of observations' thesis on the role of psychological treatment of patients of the clinic of acute poisonings. Some proposals of affective treatment of potentially suicidal patients are also presented for doctors and other medical advisors.

  14. Metabolic Heat Regenerated Temperature Swing Adsorption for CO(sub 2) and Heat Removal/Rejection in a Martian PLSS

    NASA Technical Reports Server (NTRS)

    Iacomini, Christine; Powers, Aaron; Bowers, Chad; Straub-Lopez, Katie; Anderson, Grant; MacCallum, Taber; Paul, Heather

    2007-01-01

    Two of the fundamental problems facing the development of a Portable Life Support System (PLSS) for use on Mars, are (i) heat rejection (because traditional technologies use sublimation of water, which wastes a scarce resource and contaminates the premises), and (ii) rejection of CO2 in an environment with a ppCO2 of 0.4-0.9 kPa. Patent-pending Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is being developed to address both these challenges. The technology utilizes an adsorbent that when cooled with liquid CO2 to near sublimation temperatures (195K) removes metabolically-produced CO2 in the vent loop. Once fully loaded, the adsorbent is then warmed externally by the vent loop (approx. 300K), rejecting the captured CO2 to Mars ambient. Two beds are used to effect a continuous cycle of CO2 removal/rejection as well as facilitate heat exchange out of the vent loop. Any cryogenic fluid can be used in the application; however, since CO2 is readily available at Mars and can be easily produced and stored on the Martian surface, the solution is rather elegant and less complicated when employing liquid CO2. As some metabolic heat will need to be rejected anyway, finding a practical use for metabolic heat is also an overall benefit to the PLSS. To investigate the feasibility of the technology, a series of experiments was conducted which lead to the selection and partial characterization of an appropriate adsorbent. The adsorbent NaX successfully removed CO2 from a simulated vent loop at the prescribed temperature swing anticipated during PLSS operating conditions on Mars using a cryogenic fluid. Thermal conductivity of the adsorbent was also measured to eventually aid in a demonstrator design of the technology. These results provide no show stoppers to the development of MTSA technology and allow its development to focus on other design challenges as listed in the conclusions.

  15. Clinical and laboratory assessment of dehydration severity in children with acute gastroenteritis.

    PubMed

    Parkin, Patricia C; Macarthur, Colin; Khambalia, Amina; Goldman, Ran D; Friedman, Jeremy N

    2010-03-01

    To evaluate clinical and laboratory assessment of dehydration severity in children, 1 to 36 months, with acute gastroenteritis. Clinical and laboratory measures and weight change following rehydration were collected for enrolled children. Pediatric emergency department. Likelihood ratio (LR+) and 95% confidence interval (CI): for a clinical score of 0, the LR+ was 2.2 (95% CI = 0.9-5.3); for a clinical score of 1 to 4, the LR+ was 1.3 (95% CI = 0.90-1.74); for a clinical score of 5 to 8, the LR+ was 5.2 (95% CI = 2.2-12.8); for a venous pH <7.32, the LR+ was 7.2 (95% CI = 2.4-21.9); and for serum bicarbonate <18 mmol/L, the LR+ was 11.6 (95% CI = 3.5-38.0). Clinicians may find it useful to incorporate the Clinical Dehydration Scale and laboratory measures into clinical decision-making algorithms to assess dehydration severity in children with acute gastroenteritis.

  16. Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement.

    PubMed

    Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

    2012-01-01

    Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). In vivo toxicity studies were performed in male balb 'C' mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement.

  17. Clinical practice guidelines for the management of acute limb compartment syndrome following trauma.

    PubMed

    Wall, Christopher J; Lynch, Joan; Harris, Ian A; Richardson, Martin D; Brand, Caroline; Lowe, Adrian J; Sugrue, Michael

    2010-03-01

    Acute compartment syndrome is a serious and not uncommon complication of limb trauma. The condition is a surgical emergency, and is associated with significant morbidity if not managed appropriately. There is variation in management of acute limb compartment syndrome in Australia. Clinical practice guidelines for the management of acute limb compartment syndrome following trauma were developed in accordance with Australian National Health and Medical Research Council recommendations. The guidelines were based on critically appraised literature evidence and the consensus opinion of a multidisciplinary team involved in trauma management who met in a nominal panel process. Recommendations were developed for key decision nodes in the patient care pathway, including methods of diagnosis in alert and unconscious patients, appropriate assessment of compartment pressure, timing and technique of fasciotomy, fasciotomy wound management, and prevention of compartment syndrome in patients with limb injuries. The recommendations were largely consensus based in the absence of well-designed clinical trial evidence. Clinical practice guidelines for the management of acute limb compartment syndrome following trauma have been developed that will support consistency in management and optimize patient health outcomes.

  18. The Lunch Bunch: an innovative strategy to combat depression and delirium through socialization in elderly sub-acute medicine patients.

    PubMed

    Feyerer, Margot; Kruk, Dawn; Bartlett, Nicole; Rodney, Kathy; McKenzie, Cyndi; Green, Patrice; Keller, Lisa; Adcroft, Pat

    2013-01-01

    Hospitalized sub-acute medicine patients face challenges to their functional and cognitive abilities as they await transfer to long-term care facilities or return home. The Continuous Quality Improvement (CQI) Council, representing a multidisciplinary team of healthcare professionals working in the Sub-Acute Medicine Unit (SAMU), implemented a twice-weekly lunch program called the Lunch Bunch in order to combat depression and delirium in our elderly and cognitively impaired patients. The Lunch Bunch initiative includes chaplains, nurses and physiotherapists who have provided a framework through which essential socialization and exercise for this vulnerable population is facilitated. Providing a means for both mental and physical stimulation also allows patients to open up and discuss hidden feelings of loneliness and isolation, thereby beginning a journey of spiritual and emotional healing.

  19. Limbic Justice—Amygdala Involvement in Immediate Rejection in the Ultimatum Game

    PubMed Central

    Fransson, Peter; Petrovic, Predrag; Johannesson, Magnus; Ingvar, Martin

    2011-01-01

    Imaging studies have revealed a putative neural account of emotional bias in decision making. However, it has been difficult in previous studies to identify the causal role of the different sub-regions involved in decision making. The Ultimatum Game (UG) is a game to study the punishment of norm-violating behavior. In a previous influential paper on UG it was suggested that frontal insular cortex has a pivotal role in the rejection response. This view has not been reconciled with a vast literature that attributes a crucial role in emotional decision making to a subcortical structure (i.e., amygdala). In this study we propose an anatomy-informed model that may join these views. We also present a design that detects the functional anatomical response to unfair proposals in a subcortical network that mediates rapid reactive responses. We used a functional MRI paradigm to study the early components of decision making and challenged our paradigm with the introduction of a pharmacological intervention to perturb the elicited behavioral and neural response. Benzodiazepine treatment decreased the rejection rate (from 37.6% to 19.0%) concomitantly with a diminished amygdala response to unfair proposals, and this in spite of an unchanged feeling of unfairness and unchanged insular response. In the control group, rejection was directly linked to an increase in amygdala activity. These results allow a functional anatomical detection of the early neural components of rejection associated with the initial reactive emotional response. Thus, the act of immediate rejection seems to be mediated by the limbic system and is not solely driven by cortical processes, as previously suggested. Our results also prompt an ethical discussion as we demonstrated that a commonly used drug influences core functions in the human brain that underlie individual autonomy and economic decision making. PMID:21559322

  20. Anti-inflammatory activity and sub-acute toxicity of artemetin.

    PubMed

    Sertié, J A; Basile, A C; Panizza, S; Matida, A K; Zelnik, R

    1990-02-01

    The 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone (artemetin) from Cordia verbenacea DC (Boraginaceae) showed marked anti-inflammatory activity using various experimental models in rats. Artemetin significantly inhibited carrageenin-induced paw edema following oral doses from 30.4 to 153.9 mg.kg-1. The doses of 102.6 and 153.9 mg.kg-1 showed an inhibitory effect similar to that of 50.0 mg.kg-1 of calcium phenylbutazone. The ED50 value of artemetin in rats was estimated to be 67.07 mg.kg-1. Repeated administration of artemetin at doses of 67.07 mg.kg-1 for a 6-day period reduced granuloma formation with a response comparable to that of 20.0 mg.kg-1 of calcium phenylbutazone. This same dose of artemetin also reduced the vascular permeability to intracutaneous histamine. Sub-acute toxicological experiments indicated a very low toxicity.

  1. Clinical features of autoimmune hepatitis with acute presentation: a Japanese nationwide survey.

    PubMed

    Joshita, Satoru; Yoshizawa, Kaname; Umemura, Takeji; Ohira, Hiromasa; Takahashi, Atsushi; Harada, Kenichi; Hiep, Nguyen Canh; Tsuneyama, Koichi; Kage, Masayoshi; Nakano, Masayuki; Kang, Jong-Hon; Koike, Kazuhiko; Zeniya, Mikio; Yasunaka, Tetsuya; Takaki, Akinobu; Torimura, Takuji; Abe, Masanori; Yokosuka, Osamu; Tanaka, Atsushi; Takikawa, Hajime

    2018-02-23

    Autoimmune hepatitis (AIH) is characterized by progressive inflammation and necrosis of hepatocytes and eventually leads to a variety of phenotypes, including acute liver dysfunction, chronic progressive liver disease, and fulminant hepatic failure. Although the precise mechanisms of AIH are unknown, environmental factors may trigger disease onset in genetically predisposed individuals. Patients with the recently established entity of AIH with acute presentation often display atypical clinical features that mimic those of acute hepatitis forms even though AIH is categorized as a chronic liver disease. The aim of this study was to identify the precise clinical features of AIH with acute presentation. Eighty-six AIH patients with acute presentation were retrospectively enrolled from facilities across Japan and analyzed for clinical features, histopathological findings, and disease outcomes. Seventy-five patients were female and 11 were male. Patient age ranged from adolescent to over 80 years old, with a median age of 55 years. Median alanine transaminase (ALT) was 776 U/L and median immunoglobulin G (IgG) was 1671 mg/dL. There were no significant differences between genders in terms of ALT (P = 0.27) or IgG (P = 0.51). The number of patients without and with histopathological fibrosis was 29 and 57, respectively. The patients with fibrosis were significantly older than those without (P = 0.015), but no other differences in clinical or histopathological findings were observed. Moreover, antinuclear antibody (ANA)-positive (defined as × 40, N = 63) and -negative (N = 23) patients showed no significant differences in clinical or histopathological findings or disease outcomes. Twenty-five patients experienced disease relapse and two patients died during the study period. ALP ≥ 500 U/L [odds ratio (OR) 3.20; 95% confidence interval (CI) 1.12-9.10; P < 0.030] and GGT ≥ 200 U/L (OR 2.98; 95% CI 1.01-8.77; P = 0.047) were identified as

  2. Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub-clinical and clinical actinic keratosis during imiquimod treatment.

    PubMed

    Ortonne, Jean-Paul; Gupta, Girish; Ortonne, Nicolas; Duteil, Luc; Queille, Catherine; Mallefet, Pascal

    2010-07-01

    During treatment of actinic keratosis (AK) lesions with imiquimod sub-clinical lesions often become visible. It is, however, unclear whether these sub-clinical lesions would be detectable beforehand. The aim of this pilot study was to compare two techniques, cross polarized light photography (CPL) and fluorescence diagnosis (FD) using methyllevulinic acid and illumination with Wood's lamp for their ability to detect sub-clinical lesions. These findings were also compared with biopsy results taken before and after treatment with imiquimod 5% cream or vehicle. Twelve patients with at least five clinically visible AK lesions in a single contiguous 20 cm(2) area on the head were recruited. Patient eligibility was determined at the screening visit, when they were randomized to treatment. The randomization was 3:1, active to vehicle (nine treated with imiquimod, three with vehicle cream) for a total duration of 24 weeks (six clinic visits). Patients were assessed for baseline AK lesion counts (clinical and sub-clinical) at the screening visit and final counts at week 20. The number of clinically observed AK lesions was significantly lower at week 12 and week 20 compared with baseline following imiquimod treatment versus vehicle. The number of counted lesions were significantly higher using the CPL method compared with clinical counting with imiquimod treatment at baseline (8.3 +/- 3.4 vs 5.8 +/- 1.3; P = 0.027) and week 20 (4.8 +/- 2.4 vs 3.0 +/- 1.7; P = 0.02) but not in the vehicle group. The FD lesion counting method did not show a significant increase in the number of detected lesions compared with clinical analysis in the imiquimod and placebo groups but when comparisons were performed using pooled data (treatments and visits combined) the results were significant. The number of sub-clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using

  3. Update on pathogenesis and clinical management of acute pancreatitis

    PubMed Central

    Cruz-Santamaría, Dulce M; Taxonera, Carlos; Giner, Manuel

    2012-01-01

    Acute pancreatitis (AP), defined as the acute nonbacterial inflammatory condition of the pancreas, is derived from the early activation of digestive enzymes found inside the acinar cells, with variable compromise of the gland itself, nearby tissues and other organs. So, it is an event that begins with pancreatic injury, elicits an acute inflammatory response, encompasses a variety of complications and generally resolves over time. Different conditions are known to induce this disorder, although the innermost mechanisms and how they act to develop the disease are still unknown. We summarize some well established aspects. A phase sequence has been proposed: etiology factors generate other conditions inside acinar cells that favor the AP development with some systemic events; genetic factors could be involved as susceptibility and modifying elements. AP is a disease with extremely different clinical expressions. Most patients suffer a mild and limited disease, but about one fifth of cases develop multi organ failure, accompanied by high mortality. This great variability in presentation, clinical course and complications has given rise to the confusion related to AP related terminology. However, consensus meetings have provided uniform definitions, including the severity of the illness. The clinical management is mainly based on the disease´s severity and must be directed to correct the underlying predisposing factors and control the inflammatory process itself. The first step is to determine if it is mild or severe. We review the principal aspects to be considered in this treatment, as reflected in several clinical practice guidelines. For the last 25 years, there has been a global increase in incidence of AP, along with many advances in diagnosis and treatment. However, progress in knowledge of its pathogenesis is scarce. PMID:22737590

  4. Acute fascioliasis--clinical and epidemiological features of four patients in Chile.

    PubMed

    Fica, A; Dabanch, J; Farias, C; Castro, M; Jercic, M I; Weitzel, T

    2012-01-01

    Because of its infrequent and protean presentation and the lack of clinical data, the management of acute infections with the foodborne trematode Fasciola hepatica is challenging. We report four serologically confirmed cases that illustrate our experience with this parasitic infection in Chile. All patients were adults presenting with upper abdominal pain. Other symptoms included fever, nausea/vomiting, and cutaneous manifestations. In all cases, marked eosinophilia was present. All patients lived in an urban environment, and three reported the consumption of raw watercress. Computed tomography (CT) scans showed hypodense hepatic lesions, whereas ultrasonography findings were unremarkable. One patient suffered portal vein thrombosis, which might be a rare complication of acute fascioliasis. All patients were successfully treated with triclabendazole. Our case series demonstrates that patients with acute fascioliasis typically present with a combination of upper abdominal pain, marked eosinophilia, and hypodense hepatic lesions on CT imaging. Diagnosis should be confirmed by serological investigation. A history of recent consumption of raw watercress is an important finding, but in some patients the source of infection remains obscure. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  5. The delivery of clinical preventive services: acute care intervention.

    PubMed

    Hahn, D L

    1999-10-01

    . Evidence-based clinical preventive services are underutilized. We explored the major factors associated with delivery of these services in a large physician-owned community-based group practice that provided care for both fee-for-service (FFS) and health maintenance organization (HMO) patient populations. We performed a cross-sectional audit of the computerized billing data of all adult outpatients seen at least once by any primary care provider in 1995 (N = 75,621). Delivery of preventive services was stratified by age, sex, visit frequency, insurance status (FFS or HMO), and visit type (acute care only or scheduled preventive visit). Insurance status and visit type were the strongest predictors of clinical preventive service delivery. Patients with FFS coverage received 6% to 13% (absolute difference) fewer of these services than HMO patients. Acute-care-only patients received 9% to 45% fewer services than patients who scheduled preventive visits. The combination of these factors was associated with profound differences. Having insurance to pay for preventive services is an important factor in the delivery of such care. Encouraging all patients to schedule preventive visits has been suggested as a strategy for increasing delivery, but that is not practical in this setting. Assessing the need for preventive services and offering them during acute care visits has equal potential for increasing delivery.

  6. Solar Rejection Filter for Large Telescopes

    NASA Technical Reports Server (NTRS)

    Hemmati, Hamid; Lesh, James

    2009-01-01

    To reject solar radiation photons at the front aperture for large telescopes, a mosaic of large transmission mode filters is placed in front of the telescope or at the aperture of the dome. Filtering options for effective rejection of sunlight include a smaller filter down-path near the focus of the telescope, and a large-diameter filter located in the front of the main aperture. Two types of large filters are viable: reflectance mode and transmittance mode. In the case of reflectance mode, a dielectric coating on a suitable substrate (e.g. a low-thermal-expansion glass) is arranged to reflect only a single, narrow wavelength and to efficiently transmit all other wavelengths. These coatings are commonly referred to as notch filter. In this case, the large mirror located in front of the telescope aperture reflects the received (signal and background) light into the telescope. In the case of transmittance mode, a dielectric coating on a suitable substrate (glass, sapphire, clear plastic, membrane, and the like) is arranged to transmit only a single wavelength and to reject all other wavelengths (visible and near IR) of light. The substrate of the large filter will determine its mass. At first glance, a large optical filter with a diameter of up to 10 m, located in front of the main aperture, would require a significant thickness to avoid sagging. However, a segmented filter supported by a structurally rugged grid can support smaller filters. The obscuration introduced by the grid is minimal because the total area can be made insignificant. This configuration can be detrimental to a diffraction- limited telescope due to diffraction effects at the edges of each sub-panel. However, no discernable degradation would result for a 20 diffraction-limit telescope (a photon bucket). Even the small amount of sagging in each subpanel should have minimal effect in the performance of a non-diffraction limited telescope because the part has no appreciable optical power. If the

  7. Acute porphyrias: clinical spectrum of hospitalized patients.

    PubMed

    Sheerani, Mughis; Urfy, Mian Zainulsajadeen; Hassan, Ali; Islam, Zunaira; Baig, Shahid

    2007-11-01

    To determine characteristics, clinical features and triggers of acute porphyria in hospitalized patients presenting to a tertiary care center in Pakistan. Case series. The Aga Khan University Hospital, Karachi, from 1988 to 2003. Case records of 26 patients hospitalized with diagnosis were identified through computerized hospital patients' data. The diagnosis of acute porphyria was based on pertinent clinical features and laboratory investigations after exclusion of other alternative diagnosis and patients previously diagnosed as porphyric. The data was analyzed through SPSS software version 11.0. Twelve patients (46.2%) were males. Mean age was 21 years. Most common manifestation were gastrointestinal (n=22; 88.5%) followed by neurological symptoms (n=14; 54%). Neurological manifestations included seizures (n=9; 34.6%) and neuropathy (n=6; 23%). One patient presented with depression and insomnia. Family history was positive in (n=8; 30.8%). Eighteen (69%) had history of previous attacks at their presentation to the hospital. Most common precipitating factor was 'eating outside' (n=18; 69%). Porphyrias are uncommon and cryptic group of diseases. This study shows a slightly different gender distribution, earlier onset of symptoms, higher number of neuropsychiatric symptoms (especially seizures), more distal neuropathies and different precipitant in the studied subset of patients than described previously in the western studies.

  8. [Efficacy and tolerance of fenspiride in adult patients with acute respiratory tract infections].

    PubMed

    Płusa, T; Nawacka, D

    1998-12-01

    Fenspiride is an antiinflammatory drug targeted for the respiratory tract. In our study clinical efficacy and tolerance of drug were evaluated in 392 adult patients with acute respiratory tract infections. According to clinical criteria all observed symptoms were classified as mild, moderate and severe. The most of observed patients were included into moderate symptom score. Cough and nose obturation were dominant symptoms. All noticed changes in the upper respiratory tract were decreased after fenspiride therapy in 7 days trial. In 168 observed patients systemic and in 60 local acting antibiotics were successfully applied. Excellent tolerance of fenspiride was documented in 59% and good tolerance --in 34% of patients. Observed adverse reactions were classified as mild and in 20 patients fenspiride was rejected. Authors suggest that fenspiride therapy is save and successful in patient with acute respiratory tract infection. Good results in patients with bronchitis in decreasing of bronchospasm indicate fenspiride as a good tool in bronchial infection.

  9. Segmented Ge detector rejection of internal beta activity produced by neutron irradiation

    NASA Technical Reports Server (NTRS)

    Varnell, L. S.; Callas, J. L.; Mahoney, W. A.; Pehl, R. H.; Landis, D. A.

    1991-01-01

    Future Ge spectrometers flown in space to observe cosmic gamma-ray sources will incorporate segmented detectors to reduce the background from radioactivity produced by energetic particle reactions. To demonstrate the effectiveness of a segmented Ge detector in rejecting background events due to the beta decay of internal radioactivity, a laboratory experiment has been carried out in which radioactivity was produced in the detector by neutron irradiation. A Cf-252 source of neutrons was used to produce, by neutron capture on Ge-74 (36.5 percent of natural Ge) in the detector itself, Ge-75 (t sub 1/2 = 82.78 min), which decays by beta emission with a maximum electron kinetic energy of 1188 keV. By requiring that an ionizing event deposit energy in two or more of the five segments of the detector, each about 1-cm thick, the beta particles, which have a range of about 1-mm, are rejected, while most external gamma rays incident on the detector are counted. Analysis of this experiment indicates that over 85 percent of the beta events from the decay of Ge-75 are rejected, which is in good agreement with Monte Carlo calculations.

  10. Enhanced water transport and salt rejection through hydrophobic zeolite pores.

    PubMed

    Humplik, Thomas; Lee, Jongho; O'Hern, Sean; Laoui, Tahar; Karnik, Rohit; Wang, Evelyn N

    2017-12-15

    The potential of improvements to reverse osmosis (RO) desalination by incorporating porous nanostructured materials such as zeolites into the selective layer in the membrane has spurred substantial research efforts over the past decade. However, because of the lack of methods to probe transport across these materials, it is still unclear which pore size or internal surface chemistry is optimal for maximizing permeability and salt rejection. We developed a platform to measure the transport of water and salt across a single layer of zeolite crystals, elucidating the effects of internal wettability on water and salt transport through the ≈5.5 Å pores of MFI zeolites. MFI zeolites with a more hydrophobic (i.e., less attractive) internal surface chemistry facilitated an approximately order of magnitude increase in water permeability compared to more hydrophilic MFI zeolites, while simultaneously fully rejecting both potassium and chlorine ions. However, our results also demonstrated approximately two orders of magnitude lower permeability compared to molecular simulations. This decreased performance suggests that additional transport resistances (such as surface barriers, pore collapse or blockages due to contamination) may be limiting the performance of experimental nanostructured membranes. Nevertheless, the inclusion of hydrophobic sub-nanometer pores into the active layer of RO membranes should improve both the water permeability and salt rejection of future RO membranes (Fasano et al 2016 Nat. Commun. 7 12762).

  11. Enhanced water transport and salt rejection through hydrophobic zeolite pores

    NASA Astrophysics Data System (ADS)

    Humplik, Thomas; Lee, Jongho; O'Hern, Sean; Laoui, Tahar; Karnik, Rohit; Wang, Evelyn N.

    2017-12-01

    The potential of improvements to reverse osmosis (RO) desalination by incorporating porous nanostructured materials such as zeolites into the selective layer in the membrane has spurred substantial research efforts over the past decade. However, because of the lack of methods to probe transport across these materials, it is still unclear which pore size or internal surface chemistry is optimal for maximizing permeability and salt rejection. We developed a platform to measure the transport of water and salt across a single layer of zeolite crystals, elucidating the effects of internal wettability on water and salt transport through the ≈5.5 Å pores of MFI zeolites. MFI zeolites with a more hydrophobic (i.e., less attractive) internal surface chemistry facilitated an approximately order of magnitude increase in water permeability compared to more hydrophilic MFI zeolites, while simultaneously fully rejecting both potassium and chlorine ions. However, our results also demonstrated approximately two orders of magnitude lower permeability compared to molecular simulations. This decreased performance suggests that additional transport resistances (such as surface barriers, pore collapse or blockages due to contamination) may be limiting the performance of experimental nanostructured membranes. Nevertheless, the inclusion of hydrophobic sub-nanometer pores into the active layer of RO membranes should improve both the water permeability and salt rejection of future RO membranes (Fasano et al 2016 Nat. Commun. 7 12762).

  12. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in...

  13. Revisiting Traditional Risk Factors for Rejection and Graft Loss after Kidney Transplantation

    PubMed Central

    Dunn, TB; Noreen, H; Gillingham, K; Maurer, D; Ozturk, O. Goruroglu; Pruett, TL; Bray, RA; Gebel, HM; Matas, AJ

    2011-01-01

    Single antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and SAB testing of day of transplant serum as 1) unsensitized; PRA=0 (n= 178), 2) 3rd party sensitized; no DSA (n=363), or 3) donor sensitized; with DSA (n=46), and studied rejection rates, death censored graft survival (DCGS), and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p<0.0001), but not with PRA in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p<0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p=0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization. PMID:21812918

  14. Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation

    PubMed Central

    Song, Alice Tung Wan; de Mello, Evandro Sobroza; Alves, Venâncio Avancini Ferreira; Cavalheiro, Norma de Paula; Melo, Carlos Eduardo; Bonazzi, Patricia Rodrigues; Tengan, Fatima Mitiko; Freire, Maristela Pinheiro; Barone, Antonio Alci; D'Albuquerque, Luiz Augusto Carneiro; Abdala, Edson

    2015-01-01

    Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection. PMID:25742264

  15. 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

  16. Subclinical rejection associated with chronic allograft nephropathy in protocol biopsies as a risk factor for late graft loss.

    PubMed

    Moreso, F; Ibernon, M; Gomà, M; Carrera, M; Fulladosa, X; Hueso, M; Gil-Vernet, S; Cruzado, J M; Torras, J; Grinyó, J M; Serón, D

    2006-04-01

    Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death-censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine <300 micromol/L and proteinuria <1 g/day. Biopsies were evaluated according to Banff criteria. Borderline changes and acute rejection were grouped as SCR. CAN was defined as presence of interstitial fibrosis and tubular atrophy. Mean follow-up was 91 +/- 46 months. Sufficient tissue was obtained in 435 transplants. Biopsies were classified as normal (n = 186), SCR (n = 74), CAN (n = 110) and SCR with CAN (n = 65). Presence of SCR with CAN was associated with old donors, percentage of panel reactive antibodies and presence of acute rejection before protocol biopsy. Cox regression analysis showed that SCR with CAN (relative risk [RR]: 1.86, 95% confidence interval [CI]: 1.11-3.12; p = 0.02) and hepatitis C virus (RR: 2.27, 95% CI: 1.38-3.75; p = 0.01) were independent predictors of graft survival. In protocol biopsies, the detrimental effect of interstitial fibrosis/tubular atrophy on long-term graft survival is modulated by SCR.

  17. The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial

    PubMed Central

    Massee, Laura A.; Ried, Karin; Pase, Matthew; Travica, Nikolaj; Yoganathan, Jaesshanth; Scholey, Andrew; Macpherson, Helen; Kennedy, Greg; Sali, Avni; Pipingas, Andrew

    2015-01-01

    Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered. PMID:26042037

  18. The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial.

    PubMed

    Massee, Laura A; Ried, Karin; Pase, Matthew; Travica, Nikolaj; Yoganathan, Jaesshanth; Scholey, Andrew; Macpherson, Helen; Kennedy, Greg; Sali, Avni; Pipingas, Andrew

    2015-01-01

    Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered.

  19. Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

    PubMed

    Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

    2014-11-01

    The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.

  20. Ultrasound molecular imaging of acute cellular cardiac allograft rejection in rat with T-cell-specific nanobubbles.

    PubMed

    Wu, Wei; Zhang, Zhe; Zhuo, Lisha; Zhou, Lina; Liu, Ping; He, Yun; Gao, Yunhua; Li, Rui; Chen, Qinghai; Hua, Xing

    2013-09-01

    Acute rejection (AR) is one of the main obstacles of cardiac transplantation; however, a noninvasive diagnostic method, which reflects its pathologic nature, has not been developed yet. In this study, we prepared a specific nanobubbles targeting to the activated T cells and applied it in the ultrasound molecular imaging of AR in heart transplantation by myocardial contrast echocardiography (MCE). Nanobubbles loading anti-CD25 antibody (NB(specific)) or isotype control antibody (NB(nonspecific)) were prepared and then applied in the ultrasound molecular imaging by MCE in a rat model. MCE was performed in 24 allografts and 18 isografts that were divided into three groups, including days 2, 4, and 6 after transplantation. Confocal laser scanning microscopy was used to evaluate the binding of nanobubbles and T cells in four allografts and four isografts. MCE with NB(specific) in allograft showed a "delayed enhancement," and the time-intensity curve presented a second peak. The intensity and time of second peak were both positively correlated with the transplant time (P<0.01) and the pathologic grade of AR (P<0.01). Confocal laser scanning microscopy demonstrated the binding of nanobubbles and lymphocytes in myocardium post-MCE with NB(specific). Ultrasound molecular imaging of AR after heart transplantation can be achieved by using MCE with the nanobubbles targeted to T cells. The appearance of delayed enhancement indicates the occurrence of AR, and the intensity and time of the second peak in time-intensity curve provide potential quantitative indications for diagnosis and severity of AR.

  1. 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 to...

  2. 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 to...

  3. A single-center retrospective clinicopathologic study of endomyocardial biopsies after heart transplant at Baskent University Hospital in Ankara, 1993-2014.

    PubMed

    Terzi, Ayşen; Sezgin, Atilla; Tunca, Zeynep; Deniz, Ebru; Ayva, Ebru Şebnem; Haberal Reyhan, Nihan; Müderrisoğlu, Haldun; Özdemir, Binnaz Handan

    2015-04-01

    The purpose of this study was to investigate the frequency and prognostic importance of acute cellular rejection after heart transplant. All 84 heart transplant patients at our center from January 1993 to January 2014, including all 576 endomyocardial biopsies, were evaluated with retrospective review of clinical records and endomyocardial biopsies. Routine and clinically indicated endomyocardial biopsies after heart transplant were graded for acute cellular rejection (2005 International Society for Heart and Lung Transplantation Working Formulation). Survival analysis was performed using Kaplan-Meier method. There were 61 male (73%) and 23 female recipients. Median age at heart transplant was 29 years (range, 1-62 y). Posttransplant early mortality rate was 17.9% (15 patients). In the other 69 patients, 23 patients died and 46 patients (66.7%) were alive at mean 69.3 ± 7.2 months after heart transplant. Mean follow-up was 35.4 ± 29.8 months (range, 0.07-117.5 mo). Mean 8.4 ± 4.2 endomyocardial biopsies (range, 1-19 biopsies) were performed per patient. Median first biopsy time was 7 days (range, 1-78 d). The frequency of posttransplant acute cellular rejection was 63.8% (44 of 69 patients) by histopathology; 86% patients experienced the first episode of acute cellular rejection within 6 months after transplant. There were 18 patients with acute cellular rejection ≥ grade 2R on ≥ 1 endomyocardial biopsy in 44 patients with acute cellular rejection. No significant difference was observed between survival rates of patients with grade 1R or ≥ grade 2R acute cellular rejection, or between survival rates of patients with or without diagnosis of any grade of acute cellular rejection. Acute cellular rejection was not related to any prognostic risk factor. Acute cellular rejection had no negative effect on heart recipient long-term survival, but it was a frequent complication after heart transplant, especially within the first 6 months.

  4. [The clinical classification of acute otitis media with special reference to tympanometry].

    PubMed

    Subbotina, M V

    We have developed a new clinical classification of acute otitis media (AOM) based on the previously proposed classifications of V.T. Palchun with co-workers (1997) and J. Jeger (1970) in which the letter near the stage of the pathological process roughly corresponds to the type of the tympanogram as follows: stage I (acute tubootitis): A, B, C; stage II (acute catarrhal otitis media): A, B, C; stage III (acute purulent otitis media, perforation stage); stage IV (acute purulent otitis media, post-perforation stage); stage V (resolution of otitis media): A - convalescence or recovery, B1 - exudate present in the tympanic cavity; B2 - persisting perforation; C - block of the auditory tube, O - the development of complications. This classification implies the necessity of tympanometry at the stage of diagnostics of AOM although it is not mandatory because the detection of exudate as a result of paracentesis at any of the stages of otitis media will allow to designate the stage of otitis either by letter A, B or C. The application of the new classification described in this article permits to more accurately than before determine the character of the pathological process in the middle ear during the course of acute otitis media which is of special importance in the clinical pediatric practice for the timely and adequate treatment of the children.

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

    PubMed

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

    1995-06-15

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

  6. Rejecting salient distractors: Generalization from experience.

    PubMed

    Vatterott, Daniel B; Mozer, Michael C; Vecera, Shaun P

    2018-02-01

    Distraction impairs performance of many important, everyday tasks. Attentional control limits distraction by preferentially selecting important items for limited-capacity cognitive operations. Research in attentional control has typically investigated the degree to which selection of items is stimulus-driven versus goal-driven. Recent work finds that when observers initially learn a task, the selection is based on stimulus-driven factors, but through experience, goal-driven factors have an increasing influence. The modulation of selection by goals has been studied within the paradigm of learned distractor rejection, in which experience over a sequence of trials enables individuals eventually to ignore a perceptually salient distractor. The experiments presented examine whether observers can generalize learned distractor rejection to novel distractors. Observers searched for a target and ignored a salient color-singleton distractor that appeared in half of the trials. In Experiment 1, observers who learned distractor rejection in a variable environment rejected a novel distractor more effectively than observers who learned distractor rejection in a less variable, homogeneous environment, demonstrating that variable, heterogeneous stimulus environments encourage generalizable learned distractor rejection. Experiments 2 and 3 investigated the time course of learned distractor rejection across the experiment and found that after experiencing four color-singleton distractors in different blocks, observers could effectively reject subsequent novel color-singleton distractors. These results suggest that the optimization of attentional control to the task environment can be interpreted as a form of learning, demonstrating experience's critical role in attentional control.

  7. A core outcome set for clinical trials in acute diarrhoea.

    PubMed

    Karas, Jacek; Ashkenazi, Shai; Guarino, Alfredo; Lo Vecchio, Andrea; Shamir, Raanan; Vandenplas, Yvan; Szajewska, Hania

    2015-04-01

    Core outcome sets are the baseline for what should be measured in clinical research and, thus, should serve as a guide for what should be collected and reported. The Consensus Group on Outcome Measures Made in Pediatric Enteral Nutrition Clinical Trials, established in 2012, agreed that consensus on a core set of outcomes with agreed-upon definitions that should be measured and reported in clinical trials was needed. To achieve this goal, six working groups (WGs) were setup, including WG on acute diarrhoea, whose main goal was to develop a core outcome set for trials in acute diarrhoea. The first step identified how published outcomes related to acute diarrhoea were reported. The second focused on the methodology for determining which outcomes to measure in clinical trials. The third employed a two-phase questionnaire study using the Delphi technique to define clinically important outcomes to clinicians and parents. For therapeutic studies, the five most important outcome measures were diarrhoea duration, degree of dehydration, need for hospitalisation (or duration of hospitalisation for inpatients), the proportion of patients recovered by 48 h and adverse effects. The prophylactic core outcome set included prevention of diarrhoea, prevention of dehydration, prevention of hospitalisation and adverse effects. The outcome sets for therapy and prevention can be recommended for use in future trials of patients with gastroenteritis. Their envisioned goal is to decrease study heterogeneity and to ease the comparability of studies. WG's next step is to determine how to measure the outcomes included in the core set. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. An analysis of clinical outcomes and costs of a long term acute care hospital.

    PubMed

    Votto, John J; Scalise, Paul J; Barton, Randall W; Vogel, Cristine A

    2011-01-01

    Compare clinical outcomes and costs in a study group of long-term acute care hospital (LTCH) patients with a control group of LTCH-eligible patients in an acute care hospital. LTCHs were created to provide post-acute care services not available at other post-acute settings. This is based on the premise that these patients would otherwise have stayed at acute care hospitals as high-cost outliers. The LTCH hospital is intended to deliver care to patients more efficiently, however, there are little documented clinical and financial data regarding the comparative clinical outcomes and costs for patients. Retrospective medical and billing record review of patients from the following groups: (1) LTCH study comprising patients admitted directly from an acute care hospital to the study LTCH and discharged from the LTCH from September 2004 through August 2006; (2) a control group of LTCH-eligible, medically complex patients treated and discharged from an acute care hospital in FY 2002. The control group was selected from approximately 500 patients who had at least one of the ten most common principle diagnosis DRGs of the study LTCH with >30-day length of stay at the referring hospital and met NALTH admitting guidelines. Discharge disposition is an important outcome measure of the quality of care of medically complex patients. The in-hospital mortality rate trended lower and home discharge was 3 times higher for the LTCH study group than for the control group. As a possible result, SNF discharge of LTCH patients was approximately half that of the control group. Both mean patient cost per day and mean total cost per patient were significantly higher in the control group than in the LTCH study group. The patients in the LTCH study group had both better clinical outcomes and lower cost of care than the control group.

  9. Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement

    PubMed Central

    Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

    2012-01-01

    Objectives: Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). Materials and Methods: In vivo toxicity studies were performed in male balb ‘C’ mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. Results: No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. Conclusion: The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement. PMID:23087514

  10. Social Rejection and Alcohol Use in Daily Life

    PubMed Central

    Laws, Holly B.; Ellerbeck, Nicole E.; Rodrigues, Alyne S.; Simmons, Jessica A; Ansell, Emily B.

    2017-01-01

    Background Prior studies have found that social rejection is associated with increases in negative affect, distress, and hostility. Fewer studies, however, have examined the impact of social rejection on alcohol use, and no known studies have tested whether the impact of social rejection by close others differs from social rejection by acquaintances in its association with subsequent drinking. Methods Participants completed event-contingent reports of their social interactions and alcohol use for 14 consecutive days on smartphones. Multilevel negative binomial regression models tested whether experiencing more social rejection than usual was associated with increased drinking, and whether this association was stronger when participants were rejected by close others (e.g. friends, spouses, family members) versus strangers or acquaintances. Results Results showed a significant interaction between social rejection and relationship closeness. On days characterized by rejection by close others, the likelihood of drinking significantly increased. On days characterized by rejection by acquaintances, by contrast, there was no increase in the likelihood of drinking. There was no main effect of rejection on likelihood of drinking. Conclusions These results suggest that relationship type is a key factor in whether social rejection translates to potentially harmful behaviors, such as increased alcohol use. This finding is in contrast to many laboratory paradigms of rejection, which emphasize rejection and ostracism by strangers rather than known others. In the more naturalistic setting of measuring social interactions on smartphone in daily life, however, our findings suggest that only social rejection delivered by close others, and not strangers, led to subsequent drinking. PMID:28253539

  11. The Lived Experience of Psoriasis Patients from Social Stigma and Rejection: A Qualitative Study.

    PubMed

    Ghorbanibirgani, Alireza; Fallahi-Khoshknab, Masoud; Zarea, Kourosh; Abedi, Heidarali

    2016-07-01

    Psoriasis is a common, chronic skin disease that causes challenges such as stigma and labeling from both the community and individuals due to its effects on appearance. The objective of this study was to describe and explain the social stigma and rejection experienced by patients with psoriasis. The present research is a qualitative study with a hermeneutic phenomenological approach conducted among psoriasis patients referring to the dermatology clinic and ward of Imam Khomeini hospital in Ahvaz, Iran between June and December 2014. In this study, 15 patients with psoriasis were selected by purposeful sampling, and they were asked to express their experience of stigma and rejection. The data were collected through in-depth semi-structured interviews, and Diekelmann and colleagues' method was used for data analysis. After analysis of interviews, four themes were extracted: lack of social support, unrealistic and inappropriate labeling, rejection and isolation, and feeling of absurdity and futility. These can be indicative of the patients' experience from social stigma and rejection phenomena. Patients' experiences of stigma and rejection phenomena indicated that all aspects of their lives are affected. Moreover, these findings highlight the significance of stigma and rejection concepts in providing better care to these patients.

  12. Reward, addiction, and emotion regulation systems associated with rejection in love.

    PubMed

    Fisher, Helen E; Brown, Lucy L; Aron, Arthur; Strong, Greg; Mashek, Debra

    2010-07-01

    Romantic rejection causes a profound sense of loss and negative affect. It can induce clinical depression and in extreme cases lead to suicide and/or homicide. To begin to identify the neural systems associated with this natural loss state, we used functional magnetic resonance imaging to study 10 women and 5 men who had recently been rejected by a partner but reported they were still intensely "in love." Participants alternately viewed a photograph of their rejecting beloved and a photograph of a familiar, individual, interspersed with a distraction-attention task. Their responses while looking at their rejecter included love, despair, good, and bad memories, and wondering why this happened. Activation specific to the image of the beloved occurred in areas associated with gains and losses, craving and emotion regulation and included the ventral tegmental area (VTA) bilaterally, ventral striatum, medial and lateral orbitofrontal/prefrontal cortex, and cingulate gyrus. Compared with data from happily-in-love individuals, the regional VTA activation suggests that mesolimbic reward/survival systems are involved in romantic passion regardless of whether one is happily or unhappily in love. Forebrain activations associated with motivational relevance, gain/loss, cocaine craving, addiction, and emotion regulation suggest that higher-order systems subject to experience and learning also may mediate the rejection reaction. The results show activation of reward systems, previously identified by monetary stimuli, in a natural, endogenous, negative emotion state. Activation of areas involved in cocaine addiction may help explain the obsessive behaviors associated with rejection in love.

  13. An Evolutionary Perspective on Mate Rejection.

    PubMed

    Kelly, Ashleigh J; Dubbs, Shelli L; Barlow, Fiona Kate

    2016-01-01

    We argue that mate rejection and ex-partner relationships are important, multifaceted topics that have been underresearched in social and evolutionary psychology. Mate rejection and relationship dissolution are ubiquitous and form integral parts of the human experience. Both also carry with them potential risks and benefits to our fitness and survival. Hence, we expect that mate rejection would have given rise to evolved behavioral and psychological adaptations. Herein, we outline some of the many unanswered questions in evolutionary psychology on these topics, at each step presenting novel hypotheses about how men and women should behave when rejecting a mate or potential mate or in response to rejection. We intend these hypotheses and suggestions for future research to be used as a basis for enriching our understanding of human mating from an evolutionary perspective.

  14. Acute care clinical pharmacy practice: unit- versus service-based models.

    PubMed

    Haas, Curtis E; Eckel, Stephen; Arif, Sally; Beringer, Paul M; Blake, Elizabeth W; Lardieri, Allison B; Lobo, Bob L; Mercer, Jessica M; Moye, Pamela; Orlando, Patricia L; Wargo, Kurt

    2012-02-01

    This commentary from the 2010 Task Force on Acute Care Practice Model of the American College of Clinical Pharmacy was developed to compare and contrast the "unit-based" and "service-based" orientation of the clinical pharmacist within an acute care pharmacy practice model and to offer an informed opinion concerning which should be preferred. The clinical pharmacy practice model must facilitate patient-centered care and therefore must position the pharmacist to be an active member of the interprofessional team focused on providing high-quality pharmaceutical care to the patient. Although both models may have advantages and disadvantages, the most important distinction pertains to the patient care role of the clinical pharmacist. The unit-based pharmacist is often in a position of reacting to an established order or decision and frequently is focused on task-oriented clinical services. By definition, the service-based clinical pharmacist functions as a member of the interprofessional team. As a team member, the pharmacist proactively contributes to the decision-making process and the development of patient-centered care plans. The service-based orientation of the pharmacist is consistent with both the practice vision embraced by ACCP and its definition of clinical pharmacy. The task force strongly recommends that institutions pursue a service-based pharmacy practice model to optimally deploy their clinical pharmacists. Those who elect to adopt this recommendation will face challenges in overcoming several resource, technologic, regulatory, and accreditation barriers. However, such challenges must be confronted if clinical pharmacists are to contribute fully to achieving optimal patient outcomes. © 2012 Pharmacotherapy Publications, Inc.

  15. Sex differences in sub-clinical psychosis--results from a community study over 30 years.

    PubMed

    Rössler, Wulf; Hengartner, Michael P; Ajdacic-Gross, Vladeta; Haker, Helene; Angst, Jules

    2012-08-01

    Sex differences in schizophrenia have long been reported. They are found within almost all aspects of the disease, from incidence and prevalence, age of onset, symptomatology, and course to its psycho-social outcome. Many sex-related hypotheses have been developed about the biology, psychology, or sociology of that disease. A further approach to study sex differences would be to examine such differences in sub-clinical psychotic states as well. If factors related to full-blown psychosis were equally meaningful over the entire psychosis continuum, we should expect that "true" sex differences could also be identified in sub-clinical psychosis. Here, we studied sex differences in sub-clinical psychosis within a community cohort in Zurich, Switzerland. This population was followed for over 30 years and included males and females between the ages of 20/21 and 49/50. We applied two different measures of sub-clinical psychosis representing schizotypal signs and schizophrenia nuclear symptoms. Using cross-sectional and longitudinal analyses, we found no significant sex differences in sub-clinical psychosis over time with respect to age of onset, symptomatology, course, or psycho-social outcome. Thus it appears that sex differences in psychosis manifest themselves at the high end of the continuum (full-blown schizophrenia) rather than within the sub-threshold range. Possibly males and females have separate thresholds for certain symptoms because they are differently vulnerable or exposed to various risk factors. Copyright © 2012. Published by Elsevier B.V.

  16. Molecular alterations in acute myeloid leukemia and their clinical and therapeutical implications.

    PubMed

    Infante, María Stefania; Piris, Miguel Ángel; Hernández-Rivas, José Ángel

    2018-06-09

    Acute myeloid leukaemia is the most common form of acute leukaemia, and its incidence increases with age. The disease derives from a transformed multipotent malignant haematopoietic stem cell that acquires consequent genomic alterations. The identification of recurrent cytogenetic anomalies associated with different patterns of acute myeloid leukaemia clinical presentation has led to the incorporation of genetic markers in clinical decision-making. In addition, the observation that these anomalies may mark therapeutic responses and relapse and survival rates have been incorporated into the World Health Organisation's recent molecular classification and stratification and the European Leukaemia Net, with the aim of creating prognostic categories that help rationalise better diagnosis, prognosis, re-evaluation of the disease and the combination of therapeutic protocols in order to increase the survival rate of these patients. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  17. Demand management: an audit of chemical pathology test rejections by an electronic gate-keeping system at an academic hospital in Cape Town.

    PubMed

    Smit, Ida; Zemlin, Annalise E; Erasmus, Rajiv T

    2015-07-01

    Demand management is an area of laboratory activity, which is becoming increasingly important. Within the health-care system, demand management can be defined as the use of health resources to maximise its utility. Tygerberg Hospital has introduced an electronic gate-keeping system. Chemistry tests which generate the highest cost are subjected to this system and may be automatically rejected according to a set of rules. This study aimed: (1) to identify the number of chemistry tests rejected by the eGK; (2) to identify which of these rejected tests were subsequently restored and (3) to assess the impact of rejections on clinical outcome and cost-saving. A retrospective audit was conducted to determine the number of chemistry tests rejected and subsequently restored over a 6-month period. The case-notes of patients for whom requested tests previously rejected had been restored were randomly selected and investigated to assess clinical impact. Any cost-saving was calculated. A total of 68,480 tests were subjected to gate-keeping, and 4605 tests (6.7%) were rejected while 679 (14.7%) of these were restored by the requestor phoning the laboratory after obtaining authorisation. After examining a subset of clinical notes it was found that in most cases (80%), patient care was unaffected. The total cost saved was £ 25,387. The majority of the rejected tests were unnecessary and following rejection, real savings were made. Electronic gate-keeping is a simple, effective and sustainable method of demand management. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. 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. © 2015 by the Society for Personality and Social Psychology, Inc.

  19. Postoperative rebound of antiblood type antibodies and antibody-mediated rejection after ABO-incompatible living-related kidney transplantation.

    PubMed

    Ishida, Hideki; Kondo, Tsunenori; Shimizu, Tomokazu; Nozaki, Taiji; Tanabe, Kazunari

    2015-03-01

    The purpose of this study is to examine whether postoperative antiblood type antibody rebound is attributed to kidney allograft rejection in ABO blood type-incompatible (ABO-I) living-related kidney transplantation (KTx). A total of 191 ABO-I recipients who received ABO-I living-related KTx between 2001 and 2013 were divided into two groups: Group 1 consisted of low rebound [(≦1:32), N = 170] and Group 2 consisted of high rebound [(≧1:64), N = 21], according to the levels of the rebounded antiblood type antibodies within 1 year after transplantation. No prophylactic treatment for rejection was administered for elevated antiblood type antibodies, regardless of the levels of the rebounded antibodies. Within 1 year after transplantation, T-cell-mediated rejection was observed in 13 of 170 recipients (13/170, 8%) in Group 1 and in 2 of 21 recipients (2/21, 10%) in Group 2 (Groups 1 vs. 2, P = 0.432). Antibody-mediated rejection was observed in 15 of 170 recipients (15/170, 9%) and 2 of 21 recipients (2/21, 10%) in Groups 1 and 2, respectively (P = 0.898). In this study, we found no correlation between the postoperative antiblood type antibody rebound and the incidence of acute rejection. We concluded that no treatment is necessary for rebounded antiblood type antibodies. © 2014 Steunstichting ESOT.

  20. Acute and sub-chronic toxicological evaluation of hydro-methanolic extract of Coriandrum sativum L. seeds

    PubMed Central

    Patel, Dipak; Desai, Swati; Devkar, Ranjitsinh; Ramachandran, A.V.

    2012-01-01

    Coriandrum sativum L. (CS) seeds are known to possess therapeutic potentials against a variety of physiological disorders. This study assesses acute and sub-chronic toxicity profile of hydro-methanolic extract of CS seeds using OECD guidelines. In acute toxicity study, mice were once orally administered 1000, 3000 and 5000 mg/kg body weight of CS extract. There were no any behavioral alterations or mortality recorded in CS treated groups. The LD50 value was more than 5000 mg/kg body weight. In the sub-chronic oral toxicity study, the animals were orally administered with CS extract (1000, 2000 and 3000mg/kg body weight) daily for 28 days whereas; vehicle control group received 0.5 % carboxy methyl cellulose. There was significant reduction in food intake, body weight gain and plasma lipid profiles of CS2 and CS3 (2000 and 3000 mg/kg body weight respectively) groups as compared to the control group. However, there were no alterations in haematological profile, relative organ weights, histology and plasma markers of damage of vital organs (heart, liver and kidney). The overall finding of this study indicates that CS extract is non-toxic up to 3000 mg/kg body weight and can be considered as safe for consumption. PMID:27847445

  1. Infections and reduced functioning kidney mass induce chronic rejection in rat kidney allografts.

    PubMed

    Heemann, U W; Azuma, H; Tullius, S G; Schmid, C; Philipp, T; Tilney, N L

    1996-07-01

    The etiology of chronic rejection of kidney allografts is unknown, although hyperfiltration, acute rejection, viral infection and initial graft ischemia have been implicated. To test whether endothelial activation may be the link between these factors and chronic rejection, the endotoxin (lipopolysaccharide-LPS), a potent activator of endothelial cells, was evaluated in an established chronic rejection model. Bilaterally nephrectomized Lewis recipients of orthotopically transplanted Fisher 344 kidneys were treated briefly with low dose cyclosporine (1.5 mg/kg/day x 10). Recipients were given a non-lethal dose of LPS (2 mg) i.p. at 8 weeks and compared to allografted controls treated with vehicle. Urine protein was measured every 4 weeks. Rats in the treated group were sacrificed at 12 and 16 weeks, control animals at 12, 16 and 24 weeks (20/group) and examined histologically. In the chronically rejecting control allografts, progressive interstitial and glomerular sclerosis and vascular intimal proliferation had become apparent by 12 weeks. Infiltration of glomeruli, particularly by macrophages (M phi), and the coincident presence of cytokines were prominent, peaking at 16 weeks. LPS treatment accelerated and intensified these changes; proteinuria was more pronounced (16 weeks: 79 mg/24 h vs. 49 mg/24 h, p < 0.05). Numbers of infiltrating M phi peaked at 12 weeks in LPS treated hosts (69 c/FV vs. 27 c/FV in untreated controls, p < 0.01), accompanied by an increased upregulation of MHC class II and cytokine expression, particularly TNF alpha and PDGF around arteries and areas of infiltration. BY 16 weeks, 35 +/- 3% of glomeruli in LPS treated recipients had become sclerotic vs. 15 +/- 6% (p < 0.05) in controls, again associated with increased expression of cytokines (PDGF, TNF alpha, TGF beta), adhesion molecules (ICAM-1) and extracellular matrix proteins. Overall, the extent of chronic rejection of grafts in LPS treated rats at 16 weeks was similar to that

  2. An update of clinical management of acute intermittent porphyria

    PubMed Central

    Pischik, Elena; Kauppinen, Raili

    2015-01-01

    Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP

  3. Clinical Characteristics, Management, and Outcomes of Suspected Poststroke Acute Coronary Syndrome

    PubMed Central

    De Venecia, Toni Anne; Wongrakpanich, Supakanya; Rodriguez-Ziccardi, Mary; Yadlapati, Sujani; Kishlyansky, Marina; Rammohan, Harish Seetha; Figueredo, Vincent M.

    2017-01-01

    Background Acute coronary syndrome (ACS) can complicate acute ischemic stroke, causing significant morbidity and mortality. To date, literatures that describe poststroke acute coronary syndrome and its morbidity and mortality burden are lacking. Methods This is a single center, retrospective study where clinical characteristics, cardiac evaluation, and management of patients with suspected poststroke ACS were compared and analyzed for their association with inpatient mortality and 1-year all-cause mortality. Results Of the 82 patients, 32% had chest pain and 88% had ischemic ECG changes; mean peak troponin level was 18, and mean ejection fraction was 40%. The medical management group had older individuals (73 versus 67 years, p < 0.05), lower mean peak troponin levels (12 versus 49, p < 0.05), and lower mean length of stay (12 versus 25 days, p < 0.05) compared to those who underwent stent or CABG. Troponin levels were significantly associated with 1-year all-cause mortality. Conclusion Age and troponin level appear to play a role in the current clinical decision making for patient with suspected poststroke ACS. Troponin level appears to significantly correlate with 1-year all-cause mortality. In the management of poststroke acute coronary syndrome, optimal medical therapy had similar inpatient and all-cause mortality compared to PCI and/or CABG. PMID:29130017

  4. Acute Liver Failure in Children: The First 348 Patients in The Pediatric Acute Liver Failure Study Group

    PubMed Central

    Squires, Robert H.; Shneider, Benjamin L.; Bucuvalas, John; Alonso, Estella; Sokol, Ronald J.; Narkewicz, Michael R.; Dhawan, Anil; Rosenthal, Philip; Rodriguez-Baez, Norberto; Murray, Karen F.; Horslen, Simon; Martin, Martin G.; Lopez, M. James; Soriano, Humberto; McGuire, Brendan M.; Jonas, Maureen M.; Yazigi, Nada; Shepherd, Ross W.; Schwarz, Kathleen; Lobritto, Steven; Thomas, Daniel W.; Lavine, Joel E.; Karpen, Saul; Ng, Vicky; Kelly, Deirdre; Simonds, Nancy; Hynan, Linda S.

    2008-01-01

    Objectives To determine short-term outcome for children with acute liver failure (ALF) as it relates to etiology, clinical status, patient demographics and to determine prognostic factors. Study design A prospective, multi-center case study collecting demographic, clinical, laboratory and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and INR remained ≥ 20 seconds and/or >2, respectively, despite vitamin K. Primary outcome measures three weeks after study entry were death, death after transplant, alive with native liver, alive with transplanted organ. Results The etiology of ALF in 348 children included acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-APAP drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non-acetaminophen ALF died or underwent liver transplantation and never developed clinical encephalopathy. Conclusions Etiologies of ALF in children differ from adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation. PMID:16737880

  5. Pretransplant soluble CD30 is a better predictor of posttransplant development of donor-specific antibodies and acute vascular rejection than panel reactive antibodies.

    PubMed

    Vaidya, Smita; Partlow, David; Barnes, Titus; Gugliuzza, Kristine

    2006-12-27

    This study tests a hypothesis that pretransplant concentration of soluble CD30 (sCD30) is a better predictor of posttransplant development of donor-specific HLA antibodies (DSA) and acute vascular rejection (AVR) than panel reactive HLA antibodies (PRA). Pretransplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin-inhibitor based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven AVR episodes within first 6 months of the transplant. Posttransplant sera of patients with or without AVR were tested for the presence of DSA. AVR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared to those patients negative for both tests (36% versus 5%, p = 0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% versus 5%, p = 0.04). Of the 18 patients with AVR, 14 were positive for sCD30, and 13 of them (93%) developed DSA posttransplant (p = 0.001) Nineteen patients without AVR were tested for DSA and sCD30 concentrations. Only two of these 19 patients were positive for sCD30 and DSA. AVR was strongly associated with the patients tested positive for both the tests: DSA and sCD30 (p = 0.00007). Furthermore, patients with AVR are more likely to produce DSA than those without AVR (p = 0.02). These data support our hypothesis that patients positive for sCD30 contents are at high risk the development of DSA and AVR posttransplant regardless of their pretransplant PRA.

  6. Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome.

    PubMed

    Kocer, Belgin; Unal, Tugba; Nazliel, Bijen; Biyikli, Zeynep; Yesilbudak, Zulal; Karakas, Sirel; Irkec, Ceyla

    2008-12-01

    This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.

  7. Revisiting traditional risk factors for rejection and graft loss after kidney transplantation.

    PubMed

    Dunn, T B; Noreen, H; Gillingham, K; Maurer, D; Ozturk, O G; Pruett, T L; Bray, R A; Gebel, H M; Matas, A J

    2011-10-01

    Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single-antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third-party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death-censored graft survival (DCGS) and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  8. Reflections on clinical research in sub-Saharan Africa.

    PubMed

    Kuepfer, Irene; Burri, Christian

    2009-07-15

    The urgent need for new, safe and sustainable interventions against diseases that disproportionally affect the poor is finally receiving global attention and the funding landscape for development projects has significantly improved during the past decade. For the development of new drug and vaccine candidates, clinical trials have become the most important tool to assess their safety and efficacy. Recently, there has been a seismic shift in the number of clinical trials conducted in resource-limited settings. We discuss the current framework of clinical research in sub-Saharan Africa, from building product pipelines to the capacities needed for the conduct of trials according the harmonised Good Clinical Practice (GCP) ICH E6 guideline. We place emphasis on clinical research in neglected tropical diseases which still frequently has to be conducted with limited financial, logistical and human resources. Given those short-comings we recommend minimum standards needed at the local, national and sponsor levels to provide GCP-compliant clinical research.

  9. Case Report: Clinically amyopathic dermatomyositis presenting acutely with isolated facial edema

    PubMed Central

    Pappa, Efthymia; Gkeka, Marina; Protogerou, Asimina; Marinos, Leonidas; Loupa, Chariclia; Christopoulos, Constantinos

    2018-01-01

    A 45-year-old Asian man presented with acute-onset periorbital and facial edema associated with pyrexia. Muscle weakness was absent. Initial laboratory investigations showed an inflammatory reaction, while screening for infections was negative. Serum muscle enzyme levels were normal. He was hospitalized and treated empirically with antibiotics and corticosteroids, pending the result of facial skin and muscle biopsy. He showed a good clinical and laboratory response but an attempt to discontinue corticosteroids led to a prompt relapse of facial edema and pyrexia, associated with rising laboratory indices of inflammation. Biopsy findings were typical of dermatomyositis. Reintroduction of corticosteroid treatment resulted in complete clinical and laboratory remission. Facial edema as the sole clinical manifestation of dermatomyositis is extremely rare. There have been no previous reports of isolated facial edema in the setting of acute, clinically amyopathic dermatomyositis in adults. A high level of suspicion is required to make the diagnosis in the absence of myopathy and the hallmark cutaneous manifestations of the disease (heliotrope rash, Gottron papules). PMID:29707197

  10. Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

    PubMed

    Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C; Dworkin, Robert H; Katz, Nathaniel P; Kehlet, Henrik; Ballantyne, Jane C; Burke, Laurie B; Carragee, Eugene; Cowan, Penney; Croll, Scott; Dionne, Raymond A; Farrar, John T; Gilron, Ian; Gordon, Debra B; Iyengar, Smriti; Jay, Gary W; Kalso, Eija A; Kerns, Robert D; McDermott, Michael P; Raja, Srinivasa N; Rappaport, Bob A; Rauschkolb, Christine; Royal, Mike A; Segerdahl, Märta; Stauffer, Joseph W; Todd, Knox H; Vanhove, Geertrui F; Wallace, Mark S; West, Christine; White, Richard E; Wu, Christopher

    2016-02-01

    This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.

  11. Comparison between massage and routine physical therapy in women with sub acute and chronic nonspecific low back pain.

    PubMed

    Kamali, Fahimeh; Panahi, Fatemeh; Ebrahimi, Samaneh; Abbasi, Leila

    2014-01-01

    The aim of this study was to investigate the comparison of massage therapy and routine physical therapy on patients with sub acute and chronic nonspecific low back pain. Thirty volunteer female subjects with a sub acute or chronic nonspecific low back pain were randomly enrolled in two groups, massage therapy and routine physical therapy. After massage application, the hamstring and paravertebral muscles stretching and also stabilizing exercises were prescribed. In the routine physical therapy group, TENS, US and vibrator were used besides exercises. Pain intensity according to Numerical Rating Scale, functional disability level in accordance to Oswestry Disability Index, and modified Schober test, for measurement of flexion range of motion, before and after ten sessions of treatment were used to evaluate the effectiveness of the treatment. Pain intensity, Oswestry Disability Index and flexion range of motion had shown significant differences before and after intervention in both groups (p<0.001). The statistical analysis revealed that the massage therapy had significantly improved the pain intensity and Oswestry Disability Index compared to routine physical therapy (p=0.015, p=0.013 respectively), but the range of motion changes were not significant between two groups (p=1.00). It can be concluded that both massage therapy and routine physical therapy are useful for sub acute and chronic nonspecific low back pain treatment especially if accompanied with exercise. However, massage is more effective than other electrotherapy modalities, and it can be used alone or with electrotherapy for the treatment of patients with low back pain.

  12. 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

  13. Adenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection

    PubMed Central

    Jiang, Xinguo; Khan, Mohammad A.; Tian, Wen; Beilke, Joshua; Natarajan, Ramesh; Kosek, Jon; Yoder, Mervin C.; Semenza, Gregg L.; Nicolls, Mark R.

    2011-01-01

    Chronic rejection, manifested as small airway fibrosis (obliterative bronchiolitis [OB]), is the main obstacle to long-term survival in lung transplantation. Recent studies demonstrate that the airways involved in a lung transplant are relatively hypoxic at baseline and that OB pathogenesis may be linked to ischemia induced by a transient loss of airway microvasculature. Here, we show that HIF-1α mediates airway microvascular repair in a model of orthotopic tracheal transplantation. Grafts with a conditional knockout of Hif1a demonstrated diminished recruitment of recipient-derived Tie2+ angiogenic cells to the allograft, impaired repair of damaged microvasculature, accelerated loss of microvascular perfusion, and hastened denudation of epithelial cells. In contrast, graft HIF-1α overexpression induced via an adenoviral vector prolonged airway microvascular perfusion, preserved epithelial integrity, extended the time window for the graft to be rescued from chronic rejection, and attenuated airway fibrotic remodeling. HIF-1α overexpression induced the expression of proangiogenic factors such as Sdf1, Plgf, and Vegf, and promoted the recruitment of vasoreparative Tie2+ cells. This study demonstrates that a therapy that enhances vascular integrity during acute rejection may promote graft health and prevent chronic rejection. PMID:21606594

  14. Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion.

    PubMed

    Barbour, Helen R; Plant, Christine D; Harvey, Alan R; Plant, Giles W

    2013-09-27

    It has been shown that olfactory ensheathing glia (OEG) and Schwann cell (SCs) transplantation are beneficial as cellular treatments for spinal cord injury (SCI), especially acute and sub-acute time points. In this study, we transplanted DsRED transduced adult OEG and SCs sub-acutely (14 days) following a T10 moderate spinal cord contusion injury in the rat. Behaviour was measured by open field (BBB) and horizontal ladder walking tests to ascertain improvements in locomotor function. Fluorogold staining was injected into the distal spinal cord to determine the extent of supraspinal and propriospinal axonal sparing/regeneration at 4 months post injection time point. The purpose of this study was to investigate if OEG and SCs cells injected sub acutely (14 days after injury) could: (i) improve behavioral outcomes, (ii) induce sparing/regeneration of propriospinal and supraspinal projections, and (iii) reduce tissue loss. OEG and SCs transplanted rats showed significant increased locomotion when compared to control injury only in the open field tests (BBB). However, the ladder walk test did not show statistically significant differences between treatment and control groups. Fluorogold retrograde tracing showed a statistically significant increase in the number of supraspinal nuclei projecting into the distal spinal cord in both OEG and SCs transplanted rats. These included the raphe, reticular and vestibular systems. Further pairwise multiple comparison tests also showed a statistically significant increase in raphe projecting neurons in OEG transplanted rats when compared to SCs transplanted animals. Immunohistochemistry of spinal cord sections short term (2 weeks) and long term (4 months) showed differences in host glial activity, migration and proteoglycan deposits between the two cell types. Histochemical staining revealed that the volume of tissue remaining at the lesion site had increased in all OEG and SCs treated groups. Significant tissue sparing was

  15. Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis.

    PubMed

    Singh, Shailender; Dallenga, Tobias; Winkler, Anne; Roemer, Shanu; Maruschak, Brigitte; Siebert, Heike; Brück, Wolfgang; Stadelmann, Christine

    2017-03-17

    Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions. Furthermore, we studied the effects of Wallerian degeneration blockage on clinical severity, inflammatory pathology, acute axonal damage, and long-term axonal loss in experimental autoimmune encephalomyelitis using Wallerian degeneration slow (Wld S ) mutant mice. The highest numbers of axons undergoing Wallerian degeneration were found in the perilesional white matter of multiple sclerosis patients early in the disease course and with actively demyelinating lesions. Furthermore, Wallerian degeneration was more abundant in patients harboring chronic active as compared to chronic inactive lesions. No co-localization of neuropeptide Y-Y1 receptor, a bona fide immunohistochemical marker of Wallerian degeneration, with amyloid precursor protein, frequently used as an indicator of acute axonal transport disturbance, was observed in human and mouse tissue, indicating distinct axon-degenerative processes. Experimentally, a delay of Wallerian degeneration, as observed in Wld S mice, did not result in a reduction of clinical disability or acute axonal damage in experimental autoimmune encephalomyelitis, further supporting that acute axonal damage as reflected by axonal transport disturbances does not share common molecular mechanisms with Wallerian degeneration. Furthermore, delaying Wallerian degeneration

  16. Predicting outcome of acute non-variceal upper gastrointestinal haemorrhage without endoscopy using the clinical Rockall Score.

    PubMed

    Tham, T C K; James, C; Kelly, M

    2006-11-01

    The Rockall risk scoring system uses clinical criteria and endoscopy to identify patients at risk of adverse outcomes after acute upper gastrointestinal haemorrhage. A clinical Rockall score obtained using only the clinical criteria may be able to predict outcome without endoscopy. To validate the clinical Rockall Score in predicting outcome after acute non-variceal upper gastrointestinal haemorrhage. A retrospective observational study of consecutive patients who were admitted with non-variceal acute upper gastrointestinal haemorrhage was undertaken. Medical records were abstracted using a standardised form. 102 cases were identified (51 men and 51 women; mean age 59 years). 38 (37%) patients considered to be at low risk of adverse outcomes (clinical Rockall Score 0) had no adverse outcomes and did not require transfusion. Patients with a clinical Rockall Score of 1-3 had no adverse outcomes, although 13 of 45 (29%) patients required blood transfusions. Clinical Rockall Scores >3 (n = 19) were associated with adverse outcomes (rebleeding in 4 (21%), surgery in 1 (5%) and death in 2 (10%)). The clinical Rockall Score without endoscopy may be a useful prognostic indicator in this cohort of patients with acute non-variceal upper gastrointestinal haemorrhage. This score may reduce the need for urgent endoscopy in low-risk patients, which can instead be carried out on a more elective outpatient basis.

  17. Examination of clinical and cognitive insight in acute schizophrenia patients.

    PubMed

    Greenberger, Cheryl; Serper, Mark R

    2010-07-01

    Lack of insight or awareness of illness is a hallmark feature of schizophrenic illness and has become an increasingly important area of investigation. Although clinical insight focuses on awareness of illness factors, the concept of cognitive insight focuses on the cognitive processes involved in correcting erroneous judgments and certainty about mistaken judgments. The present study was aimed at further investigating the clinical utility and the statistical coherence of the Beck Cognitive Insight Scale (BCIS) (Beck et al., 2004) in acute schizoaffective and schizophrenia (SZ) patients. The present study examined the internal consistency of the scale, as well as its discriminative and predictive validity relative to a well-established traditional measure of clinical insight in a sample of 50 DSM-IV diagnosed SZ patients, presenting for acute inpatient treatment. The BCIS was found to be an internally consistent and a coherent measure of cognitive insight. The BCIS was unassociated with clinical insight, indicating the 2 constructs share little empirical overlap. Cognitive insight was found to be inversely associated with patients' severity of autistic preoccupation symptoms such that those individuals with more cognitive insight, exhibited fewer autistic/cognitive symptoms. Patients' clinical insight, however, was found to be inversely associated specifically with patients' severity of depression. Additionally, clinical insight was also found to be more impaired in patients residing in nursing home environments relative to their counterparts living in less restrictive settings when outside the hospital. Results are discussed in terms of the relationship between clinical and cognitive insight constructs to SZ symptom domains.

  18. The Lived Experience of Psoriasis Patients from Social Stigma and Rejection: A Qualitative Study

    PubMed Central

    Ghorbanibirgani, Alireza; Fallahi-Khoshknab, Masoud; Zarea, Kourosh; Abedi, Heidarali

    2016-01-01

    Background Psoriasis is a common, chronic skin disease that causes challenges such as stigma and labeling from both the community and individuals due to its effects on appearance. Objectives The objective of this study was to describe and explain the social stigma and rejection experienced by patients with psoriasis. Patients and Methods The present research is a qualitative study with a hermeneutic phenomenological approach conducted among psoriasis patients referring to the dermatology clinic and ward of Imam Khomeini hospital in Ahvaz, Iran between June and December 2014. In this study, 15 patients with psoriasis were selected by purposeful sampling, and they were asked to express their experience of stigma and rejection. The data were collected through in-depth semi-structured interviews, and Diekelmann and colleagues’ method was used for data analysis. Results After analysis of interviews, four themes were extracted: lack of social support, unrealistic and inappropriate labeling, rejection and isolation, and feeling of absurdity and futility. These can be indicative of the patients’ experience from social stigma and rejection phenomena. Conclusions Patients’ experiences of stigma and rejection phenomena indicated that all aspects of their lives are affected. Moreover, these findings highlight the significance of stigma and rejection concepts in providing better care to these patients. PMID:27656290

  19. Nurse students learning acute care by simulation - Focus on observation and debriefing.

    PubMed

    Abelsson, Anna; Bisholt, Birgitta

    2017-05-01

    Simulation creates the possibility to experience acute situations during nursing education which cannot easily be achieved in clinical settings. To describe how nursing students learn acute care of patients through simulation exercises, based on observation and debriefing. The study was designed as an observational study inspired by an ethnographic approach. Data was collected through observations and interviews. Data was analyzed using an interpretive qualitative content analysis. Nursing students created space for reflection when needed. There was a positive learning situation when suitable patient scenarios were presented. Observations and discussions with peers gave the students opportunities to identify their own need for knowledge, while also identifying existing knowledge. Reflections could confirm or reject their preparedness for clinical practice. The importance of working in a structured manner in acute care situations became apparent. However, negative feedback to peers was avoided, which led to a loss of learning opportunity. High fidelity simulation training as a method plays an important part in the nursing students' learning. The teacher also plays a key role by asking difficult questions and guiding students towards accurate knowledge. This makes it possible for the students to close knowledge gaps, leading to improved patient safety. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Detection of HLA-G in serum and graft biopsy associated with fewer acute rejections following combined liver-kidney transplantation: possible implications for monitoring patients.

    PubMed

    Creput, Caroline; Le Friec, Gaëlle; Bahri, Rajia; Amiot, Laurence; Charpentier, Bernard; Carosella, Edgardo; Rouas-Freiss, Nathalie; Durrbach, Antoine

    2003-11-01

    Human leukocyte antigen G (HLA-G) is a regulatory molecule that is expressed in the cytotrophoblast during implantation and is thought to allow the tolerance and the development of the semiallogeneic embryo. In vitro, HLA-G inhibits natural killer (NK) cell and CD8 T-cell cytotoxicity. HLA-G also decreases CD4 T-cell expansion. This suggests that it participates in the acceptance of allogeneic organ transplants in humans. We here describe the detection of high concentration of HLA-G in serum from liver-kidney transplant patients, but not in kidney transplant patients. This finding is supported by the ectopic expression of HLA-G in graft biopsies. Finally, its association with a low number of acute transplant rejections, especially in liver-kidney transplant patients led us to propose that HLA-G may serve to monitor transplant patients who are likely to accept their allograft and, thus, may benefit of a reduced immunosuppressive treatment.

  1. From Rejected to Accepted: Part 2--Preparing a Rejected Manuscript for a New Journal

    ERIC Educational Resources Information Center

    Stivers, Jan; Cramer, Sharon F.

    2017-01-01

    Manuscript rejection is a fact of life for academics, and should be seen as just one step in a process of revision and resubmission that typically results in publication. This manuscript is the second in a two-part series offering suggestions to help authors take action on their rejected manuscripts, including analyzing reviewer feedback, revising…

  2. Clinical presentation and course of acute hepatitis C infection in HIV-infected patients.

    PubMed

    Luetkemeyer, Annie; Hare, C Bradley; Stansell, John; Tien, Phyllis C; Charlesbois, Edwin; Lum, Paula; Havlir, Diane; Peters, Marion

    2006-01-01

    Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.

  3. Assessing the existence of dissociative PTSD in sub-acute patients of whiplash.

    PubMed

    Hansen, Maj; Hyland, Philip; Armour, Cherie; Andersen, Tonny E

    2018-03-16

    Numerous studies investigating dissociative posttraumatic stress disorder (D-PTSD) have emerged. However, there is a lack of studies investigating D-PTSD following a wider range of traumatic exposure. Thus, the present study investigates D-PTSD using latent class analysis (LCA) in sub-acute patients of whiplash and associated risk factors. The results of LCA showed a three-class solution primarily distributed according to posttraumatic stress disorder (PTSD) symptom severity and thus no indication of D-PTSD. Dissociative symptoms, psychological distress (i.e. anxiety/depression), and pain severity significantly predicted PTSD severity. Combined, the results support the component model of dissociation and PTSD, while still stressing the importance of dissociative symptoms when planning treatment for PTSD.

  4. When Rejection by One Fosters Aggression Against Many: Multiple-Victim Aggression as a Consequence of Social Rejection and Perceived Groupness

    PubMed Central

    Gaertner, Lowell; Iuzzini, Jonathan; O’Mara, Erin M.

    2008-01-01

    Two experiments examined the hypothesis that social rejection and perceived groupness function together to produce multiple-victim incidents of aggression. When a rejecter’s group membership is salient during an act of rejection, the rejectee ostensibly associates the rejecter’s group with rejection and retaliates against the group. Both experiments manipulated whether an aggregate of three persons appeared as separate individuals or members of an entity-like group and whether one of those persons rejected the participant. Consistent with the hypothesis, participants who experienced both rejection and perceived groupness behaved more aggressively against the aggregate (Experiment 1) and evidenced less favorable affective associations toward the aggregate (Experiment 2) than did participants who did not experience both rejection and perceived groupness. PMID:19079568

  5. Clinical and cognitive insight in patients with acute-phase psychosis: Association with treatment and neuropsychological functioning.

    PubMed

    Poyraz, Burç Çağri; Arikan, Mehmet Kemal; Poyraz, Cana Aksoy; Turan, Şenol; Kani, Ayşe Sakalli; Aydin, Eser; İnce, Ezgi

    2016-10-01

    The severity of psychopathology cannot fully explain deficits in the multi-dimensional construct of insight. The aim of this study was to evaluate the correlates and associations of clinical and cognitive insight in patients in an acute phase of psychosis and to analyse the impact of acute treatment on these variables. This study examined 47 inpatients who were recently hospitalized with acute exacerbation of schizophrenia. All subjects were assessed at both admission and discharge with the Positive and Negative Syndrome Scale (PANSS), Schedule for the Assessment of Insight-Expanded Version (SAI-E), Beck Cognitive Insight Scale (BCIS), and a neurocognition battery. Patients with schizophrenia gained clinical insight after treatment. Cognitive insight did not change significantly after treatment. Insight showed significant negative correlations with positive symptoms and general psychopathology, but not with negative symptoms. Clinical insight was not associated with neuropsychological functioning in this cohort. Gaining clinical insight in the acute phase of illness was associated with the remission of positive symptoms, but not with neuropsychological functioning. Some significant correlations between clinical and cognitive insights were detected, which suggests that cognitive insight contributes to clinical insight but is not treatment-dependent. Long-term treatment may be required to understand the contribution of insight to the outcome of patients with schizophrenia.

  6. Endogenous Memory CD8 T Cells Directly Mediate Cardiac Allograft Rejection

    PubMed Central

    Su, C. A.; Iida, S.; Abe, T.; Fairchild, R. L.

    2014-01-01

    Differences in levels of environmentally induced memory T cells that cross-react with donor MHC molecules are postulated to account for the efficacy of allograft tolerance inducing strategies in rodents versus their failure in nonhuman primates and human transplant patients. Strategies to study the impact of donor-reactive memory T cells on allografts in rodents have relied on the pre-transplant induction of memory T cells cross-reactive with donor allogeneic MHC molecules through recipient viral infection, priming directly with donor antigen, or adoptive transfer of donor-antigen primed memory T cells. Each approach accelerates allograft rejection and confers resistance to tolerance induction, but also biases the T cell repertoire to strong donor-reactivity. The ability of endogenous memory T cells within unprimed mice to directly reject an allograft is unknown. Here we show a direct association between increased duration of cold ischemic allograft storage and numbers and enhanced functions of early graft infiltrating endogenous CD8 memory T cells. These T cells directly mediate rejection of allografts subjected to prolonged ischemia and this rejection is resistant to costimulatory blockade. These findings recapitulate the clinically significant impact of endogenous memory T cells with donor reactivity in a mouse transplant model in the absence of prior recipient priming. PMID:24502272

  7. Isolated v-lesion represents a benign phenotype of vascular rejection of the kidney allograft- a retrospective study.

    PubMed

    Novotny, Marek; Hruba, Petra; Vichova, Petra; Maluskova, Jana; Honsova, Eva; Viklicky, Ondrej; Wohlfahrtova, Mariana

    2018-05-31

    While the detrimental impact of the humoral acute vascular rejection (AVR) phenotype is recognized, the prognostic significance of isolated v-lesion (IV) remains unclear. In this retrospective single-centre study, AVR was found in 98 out of 1015 patients (9.7%) who had undergone kidney transplantation in 2010-2014, with donor-specific antibodies (DSA) evaluated in all of them. The outcome of four AVR phenotypes was evaluated during median follow-up of 59 months; in 25 patients with IV, 18 with T cell-mediated vascular rejection (TCMRV), 19 with antibody-mediated vascular rejection (AMRV) and 36 with suspected antibody-mediated rejection (sAMRV). AVR was diagnosed mainly by for-cause biopsy (81%) early after transplantation (median 19 POD) and appeared as mild grade intimal arteritis. IV occurred in low sensitized patients after the first transplantation (96%) in the absence of DSA. IV responded satisfactorily to treatment (88%), showed no persistence of rejection in surveillance biopsy, had stable graft function, minimal proteinuria and excellent DCGS (96%). Contrary to that, Kaplan-Meier estimate of 3-year DCGS of AMRV was 66% (log rank=0.0004). Early IV represents a benign phenotype of AVR with a favourable outcome. This study prompts further research to evaluate the nature of IV before considering any change in the classification and management. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. An acute rat in vivo screening model to predict compounds that alter blood glucose and/or insulin regulation.

    PubMed

    Brott, David A; Diamond, Melody; Campbell, Pam; Zuvich, Andy; Cheatham, Letitia; Bentley, Patricia; Gorko, Mary Ann; Fikes, James; Saye, JoAnne

    2013-01-01

    Drug-induced glucose dysregulation and insulin resistance have been associated with weight gain and potential induction and/or exacerbation of diabetes mellitus in the clinic suggesting they may be safety biomarkers when developing antipsychotics. Glucose and insulin have also been suggested as potential efficacy biomarkers for some oncology compounds. The objective of this study was to qualify a medium throughput rat in vivo acute Intravenous Glucose Tolerance Test (IVGTT) for predicting compounds that will induce altered blood glucose and/or insulin levels. Acute and sub-chronic studies were performed to qualify an acute IVGTT model. Double cannulated male rats (Han-Wistar and Sprague-Dawley) were administered vehicle, olanzapine, aripiprazole or other compounds at t=-44min for acute studies and at time=-44min on the last day of dosing for sub-chronic studies, treated with dextrose (time=0min; i.v.) and blood collected using an automated Culex® system for glucose and insulin analysis (time=-45, -1, 2, 10, 15, 30, 45, 60, 75, 90, 120, 150 and 180min). Olanzapine significantly increased glucose and insulin area under the curve (AUC) values while aripiprazole AUC values were similar to control, in both acute and sub-chronic studies. All atypical antipsychotics evaluated were consistent with literature references of clinical weight gain. As efficacy biomarkers, insulin AUC but not glucose AUC values were increased with a compound known to have insulin growth factor-1 (IGF-1) activity, compared to control treatment. These studies qualified the medium throughput acute IVGTT model to more quickly screen compounds for 1) safety - the potential to elicit glucose dysregulation and/or insulin resistance and 2) efficacy - as a surrogate for compounds affecting the glucose and/or insulin regulatory pathways. These data demonstrate that the same in vivo rat model and assays can be used to predict both clinical safety and efficacy of compounds. © 2013.

  9. Clinical outcomes of lung transplant recipients with telomerase mutations.

    PubMed

    Tokman, Sofya; Singer, Jonathan P; Devine, Megan S; Westall, Glen P; Aubert, John-David; Tamm, Michael; Snell, Gregory I; Lee, Joyce S; Goldberg, Hilary J; Kukreja, Jasleen; Golden, Jeffrey A; Leard, Lorriana E; Garcia, Christine K; Hays, Steven R

    2015-10-01

    Successful lung transplantation for patients with pulmonary fibrosis from telomerase mutations may be limited by systemic complications of telomerase dysfunction, including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes in 14 lung transplant recipients with telomerase mutations. Subjects underwent lung transplantation between February 2005 and April 2014 at 5 transplant centers. Data were abstracted from medical records, focusing on outcomes reflecting post-transplant treatment effects likely to be complicated by telomerase mutations. The median age of subjects was 60.5 years (interquartile range = 52.0-62.0), 64.3% were male, and the mean post-transplant observation time was 3.2 years (SD ± 2.9). A mutation in telomerase reverse transcriptase was present in 11 subjects, a telomerase RNA component mutation was present in 2 subjects, and an uncharacterized mutation was present in 1 subject. After lung transplantation, 10 subjects were leukopenic and 5 did not tolerate lymphocyte anti-proliferative agents. Six subjects developed recurrent lower respiratory tract infections, 7 developed acute cellular rejection (A1), and 4 developed chronic lung allograft dysfunction. Eight subjects developed at least 1 episode of acute renal failure and 10 developed chronic renal insufficiency. In addition, 3 subjects developed cancer. No subjects had cirrhosis. At data censorship, 13 subjects were alive. The clinical course for lung transplant recipients with telomerase mutations is complicated by renal disease, leukopenia with intolerance of lymphocyte anti-proliferative agents, and recurrent lower respiratory tract infections. In contrast, cirrhosis was absent, acute cellular rejection was mild, and development of chronic lung allograft dysfunction was comparable to other lung transplant recipients. Although it poses challenges, lung transplantation may be feasible for patients with pulmonary fibrosis from telomerase mutations. Copyright © 2015

  10. CLINICAL AND THERAPEUTIC CORRELATIONS IN PATIENTS WITH SLIGHT ACUTE PANCREATITIS

    PubMed Central

    MUNHOZ-FILHO, Clewis Henri; BATIGÁLIA, Fernando; FUNES, Hamilton Luiz Xavier

    2015-01-01

    Background Acute pancreatitis is an inflammatory disease of the pancreas due to enzymatic autodigestion which can cause necrosis or multiple organ failure; its pathophysiology is not fully known yet. Aim To evaluate the correlation between clinical and therapeutic data in patients with mild acute pancreatitis. Methods A retrospective study in 55 medical records of patients admitted with acute mild pancreatitis was realized to analyze the association between age, leukocytosis, serum glutamic-oxaloacetic transaminase and lactate dehydrogenase, glucose, antibiotics, time admission and Ranson´s scores. Results There was a positive association between less intensive care (strict hydration, analgesia and monitoring of vital signs), early antibiotic therapy (monotherapy), early return to diet after 48 hours and laboratory control of the serum amylase and lipase (high in the first week and decreasing after 10 days, without any prognostic value). Conclusions Changes in the management of patients with mild acute pancreatitis, such as enteral nutrition, rational use of lower spectrum antibiotics and intensive care, have contributed significantly to the reduction of hospitalization time and mortality. PMID:25861064

  11. [Recent etiology and clinical features of acute viral hepatitis in a single center of Korea].

    PubMed

    Kang, Hyung Min; Jeong, Sook Hyang; Kim, Jin Wook; Lee, Donhun; Choi, Chang Kyu; Park, Young Soo; Hwang, Jin Hyuk; Kim, Nayoung; Lee, Dong Ho

    2007-12-01

    The etiology of acute viral hepatitis in Korea has been dynamically changing during the recent years. The aim of this study was to investigate the recent etiology and the clinical features of acute viral hepatitis in a single center of Korea. We performed a retrospective analysis of a prospective cohort of 55 patients who were diagnosed with acute viral hepatitis A to E during the period from May 2005 to August 2006. In addition to the clinically acute manifestations, the confirmatory serological tests were performed for the diagnosis of acute hepatitis A, B, C and E. The proportion of patients with acute viral hepatitis A, B, C, E and others were 56.4% (n=31), 12.7% (n=7), 18.2% (n=10), 9.1% (n=5) and 3.6% (n=2), respectively. The mean age of the patients with acute hepatitis A, B, C and E were 29.1+/-4.38, 38.7+/-11.72, 45.3+/-17.62 and 32.4+/-6.58 years, respectively. There was no fatal case. All cases of acute hepatitis B and six out of ten cases of acute hepatitis C recovered spontaneously. Four out of the five patients with acute hepatitis E had no history of travel to endemic area. The most common etiology of acute viral hepatitis in Korea is hepatitis A virus, and hepatitis C and B virus were the next most common causes. The sporadic cases of acute hepatitis E were not rare, and coinfection of HAV and HEV was observed. A multicenter, prospective study is warranted in the future.

  12. Feasibility and safety of early lower limb robot-assisted training in sub-acute stroke patients: a pilot study.

    PubMed

    Gandolfi, Marialuisa; Geroin, Christian; Tomelleri, Christopher; Maddalena, Isacco; Kirilova Dimitrova, Eleonora; Picelli, Alessandro; Smania, Nicola; Waldner, Andreas

    2017-12-01

    So far, the development of robotic devices for the early lower limb mobilization in the sub-acute phase after stroke has received limited attention. To explore the feasibility of a newly robotic-stationary gait training in sub-acute stroke patients. To report the training effects on lower limb function and muscle activation. A pilot study. Rehabilitation ward. Two sub-acute stroke inpatients and ten age-matched healthy controls were enrolled. Healthy controls served as normative data. Patients underwent 10 robot-assisted training sessions (20 minutes, 5 days/week) in alternating stepping movements (500 repetitions/session) on a hospital bed in addition to conventional rehabilitation. Feasibility outcome measures were compliance, physiotherapist time, and responses to self-report questionnaires. Efficacy outcomes were bilateral lower limb muscle activation pattern as measured by surface electromyography (sEMG), Motricity Index (MI), Medical Research Council (MRC) grade, and Ashworth Scale (AS) scores before and after training. No adverse events occurred. No significant differences in sEMG activity between patients and healthy controls were observed. Post-training improvement in MI and MRC scores, but no significant changes in AS scores, were recorded. Post-treatment sEMG analysis of muscle activation patterns showed a significant delay in rectus femoris offset (P=0.02) and prolonged duration of biceps femoris (P=0.04) compared to pretreatment. The robot-assisted training with our device was feasible and safe. It induced physiological muscle activations pattern in both stroke patients and healthy controls. Full-scale studies are needed to explore its potential role in post-stroke recovery. This robotic device may enrich early rehabilitation in subacute stroke patients by inducing physiological muscle activation patterns. Future studies are warranted to evaluate its effects on promoting restorative mechanisms involved in lower limb recovery after stroke.

  13. CMV allograft pancreatitis: diagnosis, treatment, and histological features.

    PubMed

    Klassen, D K; Drachenberg, C B; Papadimitriou, J C; Cangro, C B; Fink, J C; Bartlett, S T; Weir, M R

    2000-05-15

    Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.

  14. Adolescent peer-rejection persistently alters pain perception and CB1 receptor expression in female rats.

    PubMed

    Schneider, Peggy; Hannusch, Christin; Schmahl, Christian; Bohus, Martin; Spanagel, Rainer; Schneider, Miriam

    2014-02-01

    Peer-interactions are particularly important during adolescence and teenagers display enhanced sensitivity toward rejection by peers. Social rejection has been shown to induce alterations in pain perception in humans. However, the neurobiological consequences of adolescent social rejection have yet to be extensively characterized, and no appropriate animal model is available. Here, we propose inadequate playful interactions in adolescent rats as a novel animal model for social peer-rejection and examine potential long-term consequences into adulthood. Acute social pairing of female adolescent Wistar rats with an age-matched rat from the less playful Fischer344 strain was found to alter social play and decrease pain reactivity, indicating Fischer rats as inadequate social partners for Wistar animals. Therefore, in a second experiment, adolescent female Wistar rats were either reared with another Wistar rat (adequate social rearing; control) or with a Fischer rat (inadequate social rearing; play-deprived). Beginning on day 50, all Wistar rats were group housed with same-strain partners and tested for behavioral, neurobiological and endocrine differences in adulthood. Playful peer-interactions were decreased during adolescence in play-deprived animals, without affecting social contact behavior. Consequently, adult play-deprived rats showed decreased pain sensitivity and increased startle reactivity compared to controls, but did not differ in activity, anxiety-related behavior or social interaction. Both groups also differed in their endocrine stress-response, and expression levels of the cannabinoid CB1 receptor were increased in the thalamus, whereas FAAH levels were decreased in the amygdala. The present animal model therefore represents a novel approach to assess the long-term consequences of peer-rejection during adolescence. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  15. Operational and Clinical Strategies to Address Drug Cost Containment in the Acute Care Setting.

    PubMed

    McConnell, Karen J; Guzman, Oscar E; Pherwani, Nisha; Spencer, Dustin D; Van Cura, Jennifer D; Shea, Katherine M

    2017-01-01

    To provide clinical and operational strategies to generate drug cost savings in the hospital setting. A search of the PubMed database was performed with no time limit through July 2016. All original prospective and retrospective studies, peer-reviewed guidelines, consensus statements, review articles, and accompanying references were evaluated for inclusion. Only articles published in the English language were included. Investigators reviewed 937 abstracts. The review of the literature showed that acute care hospitals are under increasing financial pressures, and the pharmacy is often responsible for opportunities to manage drug costs. The literature also indicated that cost-containment strategies in the acute care setting range from pharmacy-directed activities to initiatives requiring interdisciplinary collaboration and strategic planning. Hospital pharmacies should consider establishing an interdisciplinary team that is responsible for systematically reviewing drug cost implications and leading any initiatives that are deemed necessary. Acute care settings can use various operational and clinical strategies to lower their expenditures on high-cost drugs. Operational strategies include various activities that pharmacy staff implement related to contracting, purchasing, and inventory management. Clinical strategies utilize clinical pharmacists working with interdisciplinary teams to develop and maintain a formulary, implement established-use criteria for select drugs, use dose optimization, and implement other clinical tactics aimed at cost containment. After initiatives are implemented, assessing the outcomes of the initiatives is important to determine how successful they were at lowering costs safely and effectively. Acute care hospitals can use various operational and clinical strategies to lower overall drug costs. A systematic stepwise approach is recommended to ensure relevant drugs are regularly reviewed and addressed as needed. © 2016 Pharmacotherapy

  16. Japanese quail acute exposure to methamidophos: experimental design, lethal, sub-lethal effects and cholinesterase biochemical and histochemical expression.

    PubMed

    Foudoulakis, Manousos; Balaskas, Christos; Csato, Attila; Szentes, Csaba; Arapis, Gerassimos

    2013-04-15

    We exposed the Japanese quail (Coturnix coturnix japonica) to the organophosphate methamidophos using acute oral test. Mortality and sub-lethal effects were recorded in accordance to internationally accepted protocols. In addition cholinesterases were biochemically estimated in tissues of the quail: brain, liver and plasma. Furthermore, brain, liver and duodenum cryostat sections were processed for cholinesterase histochemistry using various substrates and inhibitors. Mortalities occurred mainly in the first 1-2h following application. Sub-lethal effects, such as ataxia, ruffled feathers, tremor, salivation and reduced or no reaction to external stimuli were observed. Biochemical analysis in the brain, liver and plasma indicates a strong cholinesterase dependent inhibition with respect to mortality and sub-lethal effects of the quail. The histochemical staining also indicated a strong cholinesterase inhibition in the organs examined and the analysis of the stained sections allowed for an estimation and interpretation of the intoxication effects of methamidophos, in combination with tissue morphology visible by Haematoxylin and Eosin staining. We conclude that the use of biochemistry and histochemistry for the biomarker cholinesterase, may constitute a significantly novel approach for understanding the results obtained by the acute oral test employed in order to assess the effects of methamidophos and other chemicals known to inhibit this very important nervous system enzyme. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. 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…

  18. 1,25 Dihydroxyvitamin D circulating levels, calcitriol administration, and incidence of acute rejection, CMV infection, and polyoma virus infection in renal transplant recipients.

    PubMed

    Moscarelli, Luciano; Antognoli, Giulia; Buti, Elisa; Dervishi, Egrina; Fani, Filippo; Caroti, Leonardo; Tsalouchos, Aris; Romoli, Elena; Ghiandai, Giulia; Minetti, Enrico

    2016-10-01

    Observation that 1,25-Dihydroxyvitamin-D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy-proven acute rejection, CMV infection, BKV infection, with 1,25-Dihydroxyvitamin-D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids. During the first year, the incidence of BPAR (4% vs 11%, P=.04), CMV infection (3% vs 9%, P=.04), and BKV infection (6% vs 19%, P=.04) was significantly lower in users compared to controls. By multivariate Cox regression analysis, 1,25-Dihydroxyvitamin-D3 deficiency and no calcitriol exposure were independent risk factors for BPAR (HR=4.30, P<.005 and HR=3.25, P<.05), for CMV infection (HR=2.33, P<.05 and HR=2.31, P=.001), and for BKV infection (HR=2.41, P<.05 and HR=2.45, P=.001). After one year, users had a better renal function: eGFR was 62.5±6.7 mL/min vs 51.4±7.6 mL/min (P<.05). Only one user developed polyomavirus-associated nephropathy vs 15 controls. Two users lost their graft vs 11 controls. 1,25(OH)2-D3 deficiency circulating levels increased the risk of BPAR, CMV infection, BKV infection after kidney transplantation. Administration of calcitriol is a way to obtain adequate 1,25(OH)2-D3 circulating levels. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Incidence and clinical presentation of dysarthria and dysphagia in the acute setting following paediatric traumatic brain injury.

    PubMed

    Morgan, A T; Mageandran, S-D; Mei, C

    2010-01-01

    A lack of data on dysarthria and dysphagia outcomes for children following traumatic brain injury (TBI) limits our clinical evidence base, and poses daily challenges for the speech language pathologist (SLP) managing this group. The present study aimed to examine dysarthria and dysphagia incidence and the clinical presentation of children with these disorders in the acute phase following TBI. Incidence and characteristics were determined via a comprehensive retrospective medical chart review of children consecutively referred to a tertiary paediatric hospital over an 8-year period. Cases (n= 22 dysarthria, n= 72 dysphagia) and matched controls were compared across ancillary variables (e.g. age, severity of TBI, motor impairment). Incidence across the entire cohort was low [i.e. dysarthria (1.2%, 22/1895), dysphagia (3.8%, 72/1895)], but was markedly higher for the sub-category of children with severe TBI [e.g. dysphagia (76%, 63/83)]. Speech deficits were reported across respiration, phonation, resonance, articulation and prosody. Swallowing deficits included reduced lip closure, delayed swallow initiation, wet voice and coughing. Language and swallowing deficits were often co-morbid with dysarthria. Motor impairment was frequently co-morbid with both dysarthria and dysphagia. Cases had longer periods of hospitalization, ventilation and supplementary feeding compared with controls. Despite the low incidence of dysarthria and dysphagia across the entire TBI cohort, this sub-group may place longer-term burden on SLP services, having prolonged periods of ventilation, extended periods of hospitalization and a complex co-morbid clinical presentation compared with controls. The prevalence of co-morbid communication and swallowing impairments suggests a need for integrated rather than single discipline (i.e. dysphagia stream only) SLP services.

  20. Implementation of a recovery-oriented model in a sub-acute Intermediate Stay Mental Health Unit (ISMHU).

    PubMed

    Frost, Barry G; Turrell, Megan; Sly, Ketrina A; Lewin, Terry J; Conrad, Agatha M; Johnston, Suzanne; Tirupati, Srinivasan; Petrovic, Kerry; Rajkumar, Sadanand

    2017-01-03

    An ongoing service evaluation project was initiated following the establishment of a new, purpose-built, 20-bed sub-acute Intermediate Stay Mental Health Unit (ISMHU). This paper: provides an overview of the targeted 6-week program, operating within an Integrated Recovery-oriented Model (IRM); characterises the clients admitted during the first 16 months; and documents their recovery needs and any changes. A brief description of the unit's establishment and programs is initially provided. Client needs and priorities were identified collaboratively using the Mental Health Recovery Star (MHRS) and addressed through a range of in-situ, individual and group interventions. Extracted client and service data were analysed using descriptive statistics, paired t-tests examining change from admission to discharge, and selected correlations. The initial 154 clients (165 admissions, average stay = 47.86 days) were predominately male (72.1%), transferred from acute care (75.3%), with schizophrenia or related disorders (74.0%). Readmission rates within 6-months were 16.2% for acute and 3.2% for sub-acute care. Three MHRS subscales were derived, together with stage-of-change categories. Marked improvements in MHRS Symptom management and functioning were identified (z-change = -1.15), followed by Social-connection (z-change = -0.82) and Self-belief (z-change = -0.76). This was accompanied by a mean reduction of 2.59 in the number of pre-action MHRS items from admission to discharge (z-change = 0.98). Clinician-rated Health of the Nation Outcome Scales (HoNOS) improvements were smaller (z-change = 0.41), indicative of illness chronicity. Staff valued the elements of client choice, the holistic and team approach, program quality, review processes and opportunities for client change. Addressing high-levels of need in the 6-week timeframe was raised as a concern. This paper demonstrates that a recovery-oriented model can be successfully implemented at the

  1. Peer Group Rejection and Children's Outgroup Prejudice

    ERIC Educational Resources Information Center

    Nesdale, Drew; Durkin, Kevin; Maass, Anne; Kiesner, Jeff; Griffiths, Judith; Daly, Josh; McKenzie, David

    2010-01-01

    Two simulation studies examined the effect of peer group rejection on 7 and 9 year old children's outgroup prejudice. In Study 1, children (n = 88) pretended that they were accepted or rejected by their assigned group, prior to competing with a lower status outgroup. Results indicated that rejected versus accepted children showed increased…

  2. An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL).

    PubMed

    Khan, Maliha; Siddiqi, Rabbia; Naqvi, Kiran

    2018-06-01

    Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis, representing only about 2-5% of acute leukemia cases. The blast cells of MPAL express multilineage immunophenotypic markers and may have a shared B/T/myeloid phenotype. Due to historical ambiguity in the diagnosis of MPAL, the genetics and clinical features of this disease remain poorly characterized. Based on the 2008 and 2016 World Health Organization classifications, myeloid lineage is best determined by presence of myeloperoxidase, while B and T lymphoid lineages are demonstrated by CD19 and cytoplasmic CD3 expression. MPAL typically carries a worse prognosis than either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). Given the rarity of MPAL, there is a lack of prospective trial data to guide therapy; treatment generally relies on ALL-like regimens followed by consolidation chemotherapy or hematopoietic stem cell transplant (HSCT). Here, we review the updated classification, biology, clinical features, and treatment approach to MPAL.

  3. Does perceived parental rejection make adolescents sad and mad? The association of perceived parental rejection with adolescent depression and aggression.

    PubMed

    Hale, William W; Van Der Valk, Inge; Engels, Rutger; Meeus, Wim

    2005-06-01

    To research the association of perceived parental rejection to adolescent depression and aggression. This study focused on 1329 Dutch junior high and high school students (47.9% males and 52.1% females; age range 10-19 years) that completed depression, aggression and perceived parental rejection questionnaires. The data were analyzed by structural equation modeling that assumed a relationship between perceived parental rejection and adolescent aggression, as mediated by adolescent depression. Perceived parental rejection, mediated through adolescent depression, explains aggressive behaviors of adolescents, as tested by a mediation model. Additionally, the fit of this mediation model is somewhat enhanced when direct paths from perceived parental rejection to aggression are included. Further analysis demonstrates that these effects are also somewhat dependent on the gender and the age of the adolescents, as would be expected in light of previous studies of these cohorts. The study of perceived parental rejection should receive the same attention in the research of the development of both adolescent depression and aggression, as has been the case for adolescent peer rejection.

  4. Natural history of left ventricular mechanics in transplanted hearts: relationships with clinical variables and genetic expression profiles of allograft rejection.

    PubMed

    Eleid, Mackram F; Caracciolo, Giuseppe; Cho, Eun Joo; Scott, Robert L; Steidley, D Eric; Wilansky, Susan; Arabia, Francisco A; Khandheria, Bijoy K; Sengupta, Partho P

    2010-10-01

    The aim of this study was to explore the temporal evolution of left ventricular (LV) mechanics in relation to clinical variables and genetic expression profiles implicated in cardiac allograft function. Considerable uncertainty exists regarding the range and determinants of variability in LV systolic performance in transplanted hearts (TXH). Fifty-one patients (mean age 53 ± 12 years; 37 men) underwent serial assessment of echocardiograms, cardiac catheterization, gene expression profiles, and endomyocardial biopsy data within 2 weeks and at 3, 6, 12, and 24 months after transplantation. Two-dimensional speckle-tracking data were compared between patients with TXH and 37 controls (including 12 post-coronary artery bypass patients). Post-transplantation mortality and hospitalizations were recorded with a median follow-up period of 944 days. Global longitudinal strain (LS) and radial strain remained attenuated in patients with TXH at all time points (p < 0.001 and p = 0.005), independent of clinical rejection episodes. Failure to improve global LS at 3 months (≥ 1 SD) was associated with higher incidence of death and cardiac events (hazard ratio: 5.92; 95% confidence interval: 1.96 to 17.91; p = 0.049). Multivariate analysis revealed gene expression score as the only independent predictor of global LS (R(2) = 0.53, p = 0.005), with SEMA7A gene expression having the highest correlation with global LS (r = -0.84, p < 0.001). Speckle tracking-derived LV strains are helpful in estimating the burden of LV dysfunction in patients with TXH that evolves independent of biopsy-detected cellular rejection. Failure to improve global LS at 3 months after transplantation is associated with a higher incidence of death and cardiac events. Serial changes in LV mechanics correlate with peripheral blood gene expression profiles and may affect the clinical assessment of long-term prognosis in patients with TXH. Copyright © 2010 American College of Cardiology Foundation. Published by

  5. The challenge of detecting herds sub-clinically infected with Actinobacillus pleuropneumoniae.

    PubMed

    Gottschalk, Marcelo

    2015-10-01

    The introduction into a naïve herd of animals sub-clinically infected with Actinobacillus pleuropneumoniae (App) is frequently the cause of clinical pleuropneumonia and the identification of such infected herds is a priority in the control of disease. Different serological tests for App have been developed and a number of these are routinely used. Some are species-specific whereas others identify more specifically the serotype/serogroup involved which requires updated information about important serotypes recovered from diseased pigs in a given area/country. Serotyping methods based on molecular techniques have been developed lately and are ready to be used by most diagnostic laboratories. When non-conclusive serological results are obtained, direct detection of App from tonsils is sometimes attempted. This review addresses different techniques and approaches used to monitor herds sub-clinically infected by this important pathogen. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Comparison of treatment effect of neuromuscular electrical stimulation and thermal-tactile stimulation on patients with sub-acute dysphagia caused by stroke.

    PubMed

    Byeon, Haewon; Koh, Hyeung Woo

    2016-06-01

    [Purpose] The effectiveness of neuromuscular electrical stimulation in the rehabilitation of swallowing remains controversial. This study compared the effectiveness of neuromuscular electrical stimulation and thermal tactile oral stimulation, a traditional swallowing recovery treatment, in patients with sub-acute dysphagia caused by stroke. [Subjects and Methods] Subjects of the present study were 55 patients diagnosed with dysphagia caused by stroke. This study had a nonequivalent control group pretest-posttest design. [Results] Analysis of pre-post values of videofluoroscopic studies of the neuromuscular electrical stimulation and thermal tactile oral stimulation groups using a paired t-test showed no significant difference between the two groups despite both having decreased mean values of the videofluoroscopic studies after treatment. [Conclusion] This study's findings show that both neuromuscular electrical stimulation and thermal tactile oral stimulation significantly enhanced the swallowing function of patients with sub-acute dysphagia.

  7. Comparison of treatment effect of neuromuscular electrical stimulation and thermal-tactile stimulation on patients with sub-acute dysphagia caused by stroke

    PubMed Central

    Byeon, Haewon; Koh, Hyeung Woo

    2016-01-01

    [Purpose] The effectiveness of neuromuscular electrical stimulation in the rehabilitation of swallowing remains controversial. This study compared the effectiveness of neuromuscular electrical stimulation and thermal tactile oral stimulation, a traditional swallowing recovery treatment, in patients with sub-acute dysphagia caused by stroke. [Subjects and Methods] Subjects of the present study were 55 patients diagnosed with dysphagia caused by stroke. This study had a nonequivalent control group pretest-posttest design. [Results] Analysis of pre-post values of videofluoroscopic studies of the neuromuscular electrical stimulation and thermal tactile oral stimulation groups using a paired t-test showed no significant difference between the two groups despite both having decreased mean values of the videofluoroscopic studies after treatment. [Conclusion] This study’s findings show that both neuromuscular electrical stimulation and thermal tactile oral stimulation significantly enhanced the swallowing function of patients with sub-acute dysphagia. PMID:27390421

  8. On fiber rejection loss in flotation deinking

    Treesearch

    J.Y. Zhu; Freya Tan

    2005-04-01

    Reducing fiber rejection loss in flotation deinking is very important to conserve natural resources and reduce the cost of secondary fibers in paper recycling. This study examined two aspects of the problem, fiber consistency in the rejection stream and rate of Froth (or wet stream) rejection. Flotation experiments were conducted using both nylon and wood fibers in...

  9. Etiology, clinical features and management of acute recurrent pancreatitis.

    PubMed

    Deng, Yi Yun; Wang, Rui; Wu, Hao; Tang, Cheng Wei; Chen, Xin Zu

    2014-10-01

    To study the etiology and clinical features of acute recurrent pancreatitis (ARP) and to determine its optimal management and outcomes. ARP cases among acute pancreatitis patients who were admitted to the West China Hospital, Sichuan University from January 2008 to December 2012 were retrospectively collected. Their etiology, clinical features, treatments and outcomes were analyzed. Of all pancreatitis patients, 8.9% were classified as ARP. The proportions of mild and severe diseases were 85.7% and 14.3%, respectively. The common etiological factors were biliogenic (31.0%), alcohol (26.2%), hyperlipidemia (21.4%) and pancreaticobiliary malformation (15.4%). At first 46 cases were cryptogenic and among them 36 were subsequently confirmed by endoscopic retrograde cholangiopancreatography (ERCP). Among the hyperlipidemic ARP patients, 72.2% failed to routinely monitor and control serum lipids. ERCP was performed in 88 cases, and 48 also required an endoscopic sphincterotomy or calculus removal. Twenty-two patients underwent cholangiopancreatic duct stent placement, and pancreatic necrosectomy was performed on eight severe cases. The overall outcomes indicate that 8.3% of the cases progressed to chronic pancreatitis and 33.3% of the cases receiving etiological treatment were recurrence-free. There were no deaths in this study. The etiological factors of ARP are similar to those of acute pancreatitis at the first attack. The management of ARP should be fully considered based on etiological investigation. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  10. Durable Clinical and Immunologic Advantage of Living Donor Liver Transplantation in Children.

    PubMed

    Przybyszewski, Eric M; Verna, Elizabeth C; Lobritto, Steven J; Martinez, Mercedes; Vittorio, Jennifer M; Fox, Alyson N; Samstein, Benjamin; Kato, Tomoaki; Griesemer, Adam D; Emond, Jean C

    2018-06-01

    Despite high survival in pediatric living donor liver transplantation (LDLT), only 10% of liver transplants in children in the United States are from living donors, reflecting reluctance to embrace this approach. In addition to optimal timing and graft quality, LDLT may offer immunologic benefit because most donors are haploidentical parents. We sought to quantify the benefit of LDLT compared to deceased donor liver transplantation (DDLT) using granular clinical and immunologic outcomes over the long term. A retrospective cohort of children (age <18 years) surviving 1 year or longer posttransplant was evaluated to determine the impact of donor type on graft survival and immunologic outcomes. Two hundred forty-one children (177 DDLT and 64 LDLT) were assessed. In multivariable analysis, LDLT was associated with a lower rate of acute cellular rejection (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.29-0.98; P = 0.04), a lower rate of chronic rejection (HR, 0.12; 95% CI, 0.03-0.56; P = 0.007), better graft survival on monotherapy immunosuppression at 3 years posttransplant (87.7% vs 46.7%; odds ratio, 7.41; 95% CI, 2.80-19.66; P < 0.001), and a lower rate of graft loss (HR, 0.29; 95% CI, 0.10-0.88; P = 0.03). Graft type was not an independent predictor of posttransplant mortality (LDLT HR, 0.57; 95% CI, 0.16-2.01; P = 0.38). Maternal graft LDLT was associated with a lower rate of acute cellular rejection (HR, 0.13; 95% CI, 0.03-0.64; P = 0.01) and posttransplant lymphoproliferative disorder (HR, 0.04; 95% CI, 0.004-0.44; P = 0.008) compared with paternal grafts. This study demonstrates the potential benefit of LDLT, particularly with maternal grafts, for pediatric liver transplant recipients on multiple clinical parameters over long-term follow-up.

  11. Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients

    PubMed Central

    Chang, Jessica; Famulski, Konrad; Hidalgo, Luis G.; Salazar, Israel D.R.; Merino Lopez, Maribel; Matas, Arthur; Picton, Michael; de Freitas, Declan; Bromberg, Jonathan; Serón, Daniel; Sellarés, Joana; Einecke, Gunilla; Reeve, Jeff

    2015-01-01

    The prevalent renal transplant population presents an opportunity to observe the adaptive changes in the alloimmune response over time, but such studies have been limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). To circumvent these limitations, we used microarrays and conventional methods to investigate rejection in 703 unselected biopsies taken 3 days to 35 years post-transplant from North American and European centers. Using conventional methods, we diagnosed rejection in 205 biopsy specimens (28%): 67 pure TCMR, 110 pure ABMR, and 28 mixed (89 designated borderline). Using microarrays, we diagnosed rejection in 228 biopsy specimens (32%): 76 pure TCMR, 124 pure ABMR, and 28 mixed (no borderline). Molecular assessment confirmed most conventional diagnoses (agreement was 90% for TCMR and 83% for ABMR) but revealed some errors, particularly in mixed rejection, and improved prediction of failure. ABMR was strongly associated with increased graft loss, but TCMR was not. ABMR became common in biopsy specimens obtained >1 year post-transplant and continued to appear in all subsequent intervals. TCMR was common early but progressively disappeared over time. In 108 biopsy specimens obtained 10.2–35 years post-transplant, TCMR defined by molecular and conventional features was never observed. We conclude that the main cause of kidney transplant failure is ABMR, which can present even decades after transplantation. In contrast, TCMR disappears by 10 years post-transplant, implying that a state of partial adaptive tolerance emerges over time in the kidney transplant population. PMID:25377077

  12. Acute toxic nephropathies: clinical pathologic correlations.

    PubMed

    Muehrcke, R C; Volini, F I; Morris, A M; Moles, J B; Lawrence, A G

    1976-01-01

    Man's ever increasing exposure to numerous drugs and chemicals, which are the results of medical and industrial progress, produces a by-product of acute toxic nephropathies. These include acute toxic renal failure, drug-induced acute oliguric renal failure, acute hemorrhagic glomerulonephritis, nephrotic syndrome, tubular disturbances and potassium deficiency. In depth information is provided for the previously mentioned disorders.

  13. Clinical characteristics of acute hepatitis A complicated by acute kidney injury.

    PubMed

    Yu, Jung Hwan; Kim, Ja Kyung; Park, Jun Yong; Paik, Yong Han; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon; Lee, Kwan Sik

    2012-02-01

    The incidence of acute viral hepatitis A (AHA) in Korea is increasing rapidly. Additionally, we are encountering more cases with acute kidney injury (AKI), which was once regarded as a rare complication of AHA. Thus, we investigated recent aspects of the incidence and clinical characteristics of AHA complicated by AKI. Patients diagnosed with AHA at 2 referral hospitals in Seoul during the period January 2006 to December 2009 were enrolled. Of 1025 patients, 71 (6.9%) had AKI. The incidence of AKI was 3.1% in 2006, 6.0% in 2007, 8.9% in 2008, and 6.9% in 2009. Patients with AKI were predominantly male, heavy alcohol drinkers, and smokers, and also had a higher rate of underlying hypertension than patients without AKI. At admission, patients with AKI had significantly higher white blood cell counts, prolonged prothrombin times, and elevated liver enzymes, including total and direct bilirubin, gamma-glutamyltransferase, and C-reactive protein. Additionally, patients with AKI had a higher peak total bilirubin level and lower initial serum albumin level than patients without AKI. Although most patients with AHA complicated by AKI recover with conservative treatment, we should pay particular attention to patients who have risk factors for AKI.

  14. Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

    PubMed

    Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

    2017-07-12

    Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  15. Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

    PubMed

    Cozzi, E; Calabrese, F; Schiavon, M; Feltracco, P; Seveso, M; Carollo, C; Loy, M; Cardillo, M; Rea, F

    2017-02-01

    Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ET A R) and the angiotensin II receptor type 1 (AT 1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ET A R and anti-AT 1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. Rejection Sensitivity, Jealousy, and the Relationship to Interpersonal Aggression.

    PubMed

    Murphy, Anna M; Russell, Gemma

    2018-07-01

    The development and maintenance of interpersonal relationships lead individuals to risk rejection in the pursuit of acceptance. Some individuals are predisposed to experience a hypersensitivity to rejection that is hypothesized to be related to jealous and aggressive reactions within interpersonal relationships. The current study used convenience sampling to recruit 247 young adults to evaluate the relationship between rejection sensitivity, jealousy, and aggression. A mediation model was used to test three hypotheses: Higher scores of rejection sensitivity would be positively correlated to higher scores of aggression (Hypothesis 1); higher scores of rejection sensitivity would be positively correlated to higher scores of jealousy (Hypothesis 2); jealousy would mediate the relationship between rejection sensitivity and aggression (Hypothesis 3). Study results suggest a tendency for individuals with high rejection sensitivity to experience higher levels of jealousy, and subsequently have a greater propensity for aggression, than individuals with low rejection sensitivity. Future research that substantiates a link between hypersensitivity to rejection, jealousy, and aggression may provide an avenue for prevention, education, or intervention in reducing aggression within interpersonal relationships.

  17. Validation of a Simple Score to Determine Risk of Early Rejection After Pediatric Heart Transplantation.

    PubMed

    Butts, Ryan J; Savage, Andrew J; Atz, Andrew M; Heal, Elisabeth M; Burnette, Ali L; Kavarana, Minoo M; Bradley, Scott M; Chowdhury, Shahryar M

    2015-09-01

    This study aimed to develop a reliable and feasible score to assess the risk of rejection in pediatric heart transplantation recipients during the first post-transplant year. The first post-transplant year is the most likely time for rejection to occur in pediatric heart transplantation. Rejection during this period is associated with worse outcomes. The United Network for Organ Sharing database was queried for pediatric patients (age <18 years) who underwent isolated orthotopic heart transplantation from January 1, 2000 to December 31, 2012. Transplantations were divided into a derivation cohort (n = 2,686) and a validation (n = 509) cohort. The validation cohort was randomly selected from 20% of transplantations from 2005 to 2012. Covariates found to be associated with rejection (p < 0.2) were included in the initial multivariable logistic regression model. The final model was derived by including only variables independently associated with rejection. A risk score was then developed using relative magnitudes of the covariates' odds ratio. The score was then tested in the validation cohort. A 9-point risk score using 3 variables (age, cardiac diagnosis, and panel reactive antibody) was developed. Mean score in the derivation and validation cohorts were 4.5 ± 2.6 and 4.8 ± 2.7, respectively. A higher score was associated with an increased rate of rejection (score = 0, 10.6% in the validation cohort vs. score = 9, 40%; p < 0.01). In weighted regression analysis, the model-predicted risk of rejection correlated closely with the actual rates of rejection in the validation cohort (R(2) = 0.86; p < 0.01). The rejection score is accurate in determining the risk of early rejection in pediatric heart transplantation recipients. The score has the potential to be used in clinical practice to aid in determining the immunosuppressant regimen and the frequency of rejection surveillance in the first post-transplant year. Copyright © 2015 American College of Cardiology

  18. Rituximab Therapy for Rejection in Pediatric Heart Transplant.

    PubMed

    Erdogan, Ilkay; Varan, Birgul; Sezgin, Atilla; Pirat, Arash; Zeyneloglu, Pinar

    2018-04-01

    Humoral rejection is the B-cell-mediated production of immunoglobulin G antibody against the transplanted heart. Antibody-mediated rejection may be resistant to standard immunosuppressive therapy and is associated with high mortality and graft loss. Rituximab can be used to treat antibody-mediated rejection in heart transplant recipients. This retrospective study describes our experience with rituximab treatment in children with heart transplants. We present 7 pediatric patients with antibody-mediated rejection who were treated with plasma exchange and rituximab therapy. Rituximab was given at a dose of 375 mg/m2 by slow infusion in the intensive care unit after 5 days of plasmapheresis, in addition to a conventional regimen consisting of steroids, mycophenolate mofetil, and tacrolimus. The peripheral blood count and sodium, potassium, serum urea nitrogen, creatinine, aspartate aminotransferase, and alanine aminotransferase levels were measured in all patients before and after treatment. Seven patients were treated with plasma exchange and rituximab. We repeated this therapy in 5 patients because of refractoriness or recurrent rejection. After diagnoses of antibody-mediated rejection, 4 patients died within 6 months (mortality rate of 57.1%). We did not observe any adverse effects or complications related to rituximab. Rituximab can be used in humoral rejection after pediatric heart transplant. However, the success of the treatment is controversial, and further study is needed to find an effective treatment for antibody-mediated rejection and steroid-resistant cellular rejection in children.

  19. Clinical updates in adult acute lymphoblastic leukemia.

    PubMed

    Al Ustwani, Omar; Gupta, Neha; Bakhribah, Hatoon; Griffiths, Elizabeth; Wang, Eunice; Wetzler, Meir

    2016-03-01

    Acute lymphoblastic leukemia (ALL) is a clonal disease characterized by B or T lineage. Here we cover the clinical manifestations, pathophysiology and therapy for ALL. Additionally, we will discuss the evidence for minimal residual disease assessment, novel molecular targets and newly developed targeted therapies. The separation of ALL into Philadelphia chromosome positive and recently into Philadelphia-like disease represents the most exciting developments in this disease. Finally, the advent of new immunotherapeutic approaches led us to predict that in few years, ALL therapy might be based heavily on non-chemotherapeutic approaches. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection.

    PubMed

    Wang, Dong; Wu, Guo-Jun; Wu, Wei-Zhen; Yang, Shun-Liang; Chen, Jin-Hua; Wang, He; Lin, Wen-Hong; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

    2007-06-01

    Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P<0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P<0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.

  1. Survey of clinical pharmacists' knowledge of appropriateness of antimicrobial therapy for upper respiratory infections and acute bronchitis.

    PubMed

    Mainous, A G; MacFarlane, L L; Connor, M K; Green, L A; Fowler, K; Hueston, W J

    1999-04-01

    We conducted a survey to assess clinical pharmacists' recommendation of antibiotics for upper respiratory infections (URIs) and acute bronchitis. A random sample of 752 members of the American College of Clinical Pharmacy were mailed a multiple-choice survey that presented four examples consistent with clinical symptoms of the two disorders. Respondents were asked what treatment they would recommend for each example. The response rate was 59%. Pharmacists recommended antibiotics for the treatment of both URIs and acute bronchitis significantly more if patients' symptoms included discolored discharge or sputum as opposed to clear discharge. Those who were board certified were less likely than nonboard-certified pharmacists to recommend antibiotics for URIs with discolored discharge. Pharmacists who specialized in either ambulatory care or infectious disease were less likely than those in other specialties to recommend antibiotics for acute bronchitis with discolored sputum. Clinical pharmacists are similar to patients and physicians in their belief that antibiotics are appropriate for URIs and acute bronchitis with discolored discharge. Considering the role that pharmacists play as clinical consultants to physicians, greater efforts should be made to educate them regarding appropriate prescription of antibiotics.

  2. Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue

    PubMed Central

    Korutla, Laxminarayana; Habertheuer, Andreas; Yu, Ming; Rostami, Susan; Yuan, Chao-Xing; Reddy, Sanjana; Korutla, Varun; Koeberlein, Brigitte; Trofe-Clark, Jennifer; Rickels, Michael R.; Naji, Ali

    2017-01-01

    In transplantation, there is a critical need for noninvasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor-specific exosomes into recipient circulation and that the quantitation and profiling of donor intra-exosomal cargoes may constitute a biomarker platform for monitoring rejection. Here, we have tested this hypothesis in a human-into-mouse xenogeneic islet transplant model and validated the concept in clinical settings of islet and renal transplantation. In the xenogeneic model, we quantified islet transplant exosomes in recipient blood over long-term follow-up using anti-HLA antibody, which was detectable only in xenoislet recipients of human islets. Transplant islet exosomes were purified using anti-HLA antibody–conjugated beads, and their cargoes contained the islet endocrine hormone markers insulin, glucagon, and somatostatin. Rejection led to a marked decrease in transplant islet exosome signal along with distinct changes in exosomal microRNA and proteomic profiles prior to appearance of hyperglycemia. In the clinical settings of islet and renal transplantation, donor exosomes with respective tissue specificity for islet β cells and renal epithelial cells were reliably characterized in recipient plasma over follow-up periods of up to 5 years. Collectively, these findings demonstrate the biomarker potential of transplant exosome characterization for providing a noninvasive window into the conditional state of transplant tissue. PMID:28319051

  3. Biolimus-A9 polymer-free coated stent in high bleeding risk patients with acute coronary syndrome: a Leaders Free ACS sub-study

    PubMed Central

    Naber, Christoph K.; Urban, Philip; Ong, Paul J.; Valdes-Chavarri, Mariano; Abizaid, Alexandre A.; Pocock, Stuart J.; Fabbiocchi, Franco; Dubois, Christophe; Copt, Samuel; Greene, Samantha; Morice, Marie-Claude

    2017-01-01

    Aims Although a true clinical challenge, high bleeding risk patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have never been specifically studied. Leaders Free ACS, a pre-specified Leaders Free sub-study, determined efficacy, and safety of a combination of 1-month dual anti-platelet therapy (DAPT) with implantation of either a polymer-free Biolimus-A9-coated stent (BA9-DCS) or a bare-metal stent (BMS) in these patients. Methods and results Leaders Free included 2466 patients undergoing PCI who had at least 1 of 13 pre-defined factors for an increased bleeding risk. Of these, 659 ACS patients were included in this analysis (BA9-DCS 330, BMS 329). At 12-month follow-up, treatment with the BA9-DCS was more effective (clinically driven target-lesion revascularization 3.9 vs. 9.0%, P = 0.009) and safer (cumulative incidence of cardiac death, myocardial infarction, or definite or probable stent thrombosis 9.3 vs. 18.5%, P = 0.001), driven by significantly lower rates of cardiac mortality (3.4 vs. 6.9%, P = 0.049) and myocardial infarction (6.9 vs. 13.8%, P = 0.005). Conclusion We believe that the results of this sub-analysis from the Leaders Free trial are likely to significantly impact clinical practice for high bleeding risk patients presenting with an ACS: the use of a BMS can, in our view, no longer be recommended, and, given the paucity of available data for second-generation DES with shortened DAPT in these patients, the BA9-DCS should currently be considered as the device with the strongest evidence to support its use for this indication. PMID:27190095

  4. G-CSF in acute myocardial infarction - experimental and clinical findings.

    PubMed

    Ince, Hüseyin; Petzsch, Michael; Rehders, Tim C; Dunkelmann, Simone; Nienaber, Christoph A

    2006-09-01

    Early data from clinical studies suggest that intracoronary injection of autologous progenitor cells may beneficially affect postinfarction remodeling and perfusion. Beyond intracoronary infusion of autologous bone marrow mononuclear CD34+ cells (MNCCD34+), mobilization of stem cells by G-CSF has recently attracted attention because of various advantages such as the noninvasive nature of MNCCD34+ mobilization by subcutaneous injections. It is the aim of the present work to give an overview about the current experimental and clinical findings of G-CSF treatment in acute myocardial infarction.

  5. Pulmonary thromboembolic disease. Clinical management of acute and chronic disease.

    PubMed

    Torbicki, Adam

    2010-07-01

    Pulmonary thromboembolism falls between the areas of pulmonology and cardiology, internal medicine and intensive care, radiology and nuclear medicine, and hematology and cardiothoracic surgery. Depending on their clinical background, physicians faced with a patient with a pulmonary thromboembolism may speak different languages and adopt different treatment approaches. Now, however, there is an opportunity to end the Tower of Babel surrounding pulmonary thromboembolism. There is a growing acknowledgement that the key clinical problems in both acute pulmonary embolism and chronic thromboembolic pulmonary hypertension are linked to right ventricular pressure overload and right ventricular failure. As a result, cardiologists and cardiac intensive care specialists are taking an increasing interest in understanding and combating these conditions. The European Society of Cardiology was the first to elaborate comprehensive clinical practice guidelines for pulmonary thromboembolism and chronic thromboembolic pulmonary hypertension. The task forces involved in producing these guidelines included radiologists, pulmonologists, hematologists, intensive care physicians and surgeons, which ensured that the final document was universally acceptable. The aim of this article was to provide an overview of the epidemiology, risk factors, diagnosis, treatment, prognosis and prevention of acute pulmonary thromboembolism and chronic thromboembolic pulmonary hypertension, while taking into account European Society of Cardiology guidelines and incorporating new evidence where necessary.

  6. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes

    PubMed Central

    Makris, Konstantinos; Spanou, Loukia

    2016-01-01

    Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI. PMID:28303073

  7. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.

    PubMed

    Makris, Konstantinos; Spanou, Loukia

    2016-05-01

    Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI.

  8. The Good Clinical Practice guideline and its interpretation - perceptions of clinical trial teams in sub-Saharan Africa.

    PubMed

    Vischer, N; Pfeiffer, C; Joller, A; Klingmann, I; Ka, A; Kpormegbe, S K; Burri, C

    2016-08-01

    To explore the advantages and challenges of working with the Good Clinical Practice (GCP)-International Conference of Harmonization (ICH) E6 guideline and its interpretation from the perspective of clinical trial teams based in sub-Saharan Africa. We conducted 60 key informant interviews with clinical trial staff at different levels in clinical research centres in Kenya, Ghana, Burkina Faso and Senegal and thematically analysed the responses. Clinical trial teams perceived working with ICH-GCP as highly advantageous and regarded ICH-GCP as applicable to their setting and efficiently applied. Only for informed consent did some clinical trial staff (one-third) perceive the guideline as insufficiently applicable. Specific challenges included meeting the requirements for written and individual consent, conditions for impartial witnesses for illiterates or legally acceptable representatives for children, guaranteeing voluntary participation and ensuring full understanding of the consent given. It was deemed important to have ICH-GCP compliance monitored by relevant ethics committees and regulatory authorities, without having guidelines applied overcautiously. Clinical trial teams in sub-Saharan Africa perceived GCP as a helpful guideline, despite having been developed by northern organisations and despite the high administrative burden of implementing it. To mitigate consent challenges, we suggest adapting GCP and making use of the flexibility it offers. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  9. Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts.

    PubMed Central

    MacMillan-Crow, L A; Crow, J P; Kerby, J D; Beckman, J S; Thompson, J A

    1996-01-01

    Inflammatory processes in chronic rejection remain a serious clinical problem in organ transplantation. Activated cellular infiltrate produces high levels of both superoxide and nitric oxide. These reactive oxygen species interact to form peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine. We identified enhanced immunostaining for nitrotyrosine localized to tubular epithelium of chronically rejected human renal allografts. Western blot analysis of rejected tissue demonstrated that tyrosine nitration was restricted to a few specific polypeptides. Immunoprecipitation and amino acid sequencing techniques identified manganese superoxide dismutase, the major antioxidant enzyme in mitochondria, as one of the targets of tyrosine nitration. Total manganese superoxide dismutase protein was increased in rejected kidney, particularly in the tubular epithelium; however, enzymatic activity was significantly decreased. Exposure of recombinant human manganese superoxide dismutase to peroxynitrite resulted in a dose-dependent (IC50 = 10 microM) decrease in enzymatic activity and concomitant increase in tyrosine nitration. Collectively, these observations suggest a role for peroxynitrite during development and progression of chronic rejection in human renal allografts. In addition, inactivation of manganese superoxide dismutase by peroxynitrite may represent a general mechanism that progressively increases the production of peroxynitrite, leading to irreversible oxidative injury to mitochondria. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8876227

  10. Post-transplant soluble CD30 levels are associated with early subclinical rejection in kidney transplantation.

    PubMed

    Grenzi, Patricia C; Campos, Érika F; Silva, Hélio T; Felipe, Claudia R; Franco, Marcelo F; Soares, Maria F; Medina-Pestana, José O; Gerbase-DeLima, Maria

    2015-03-01

    Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. The study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels ≥ 61.88 ng/mL (P = 0.004), younger recipient age (P = 0.030) and non-Caucasian ethnicity (P = 0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r = 0.385, P = 0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Prognostic and Pathogenetic Value of Combining Clinical and Biochemical Indices in Patients With Acute Lung Injury

    PubMed Central

    Koyama, Tatsuki; Billheimer, D. Dean; Wu, William; Bernard, Gordon R.; Thompson, B. Taylor; Brower, Roy G.; Standiford, Theodore J.; Martin, Thomas R.; Matthay, Michael A.

    2010-01-01

    Background: No single clinical or biologic marker reliably predicts clinical outcomes in acute lung injury (ALI)/ARDS. We hypothesized that a combination of biologic and clinical markers would be superior to either biomarkers or clinical factors alone in predicting ALI/ARDS mortality and would provide insight into the pathogenesis of clinical ALI/ARDS. Methods: Eight biologic markers that reflect endothelial and epithelial injury, inflammation, and coagulation (von Willebrand factor antigen, surfactant protein D [SP-D]), tumor necrosis factor receptor-1, interleukin [IL]-6, IL-8, intercellular adhesion molecule-1, protein C, plasminogen activator inhibitor-1) were measured in baseline plasma from 549 patients in the ARDSNet trial of low vs high positive end-expiratory pressure. Mortality was modeled with multivariable logistic regression. Predictors were selected using backward elimination. Comparisons between candidate models were based on the receiver operating characteristics (ROC) and tests of integrated discrimination improvement. Results: Clinical predictors (Acute Physiology And Chronic Health Evaluation III [APACHE III], organ failures, age, underlying cause, alveolar-arterial oxygen gradient, plateau pressure) predicted mortality with an area under the ROC curve (AUC) of 0.82; a combination of eight biomarkers and the clinical predictors had an AUC of 0.85. The best performing biomarkers were the neutrophil chemotactic factor, IL-8, and SP-D, a product of alveolar type 2 cells, supporting the concept that acute inflammation and alveolar epithelial injury are important pathogenetic pathways in human ALI/ARDS. Conclusions: A combination of biomarkers and clinical predictors is superior to clinical predictors or biomarkers alone for predicting mortality in ALI/ARDS and may be useful for stratifying patients in clinical trials. From a pathogenesis perspective, the degree of acute inflammation and alveolar epithelial injury are highly associated with the

  12. Rejected by Peers--Attracted to Antisocial Media Content: Rejection-Based Anger Impairs Moral Judgment among Adolescents

    ERIC Educational Resources Information Center

    Plaisier, Xanthe S.; Konijn, Elly A.

    2013-01-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents to select antisocial media content by tying…

  13. Clinical signs of dysphagia in infants with acute viral bronchiolitis☆

    PubMed Central

    Barbosa, Lisiane De Rosa; Gomes, Erissandra; Fischer, Gilberto Bueno

    2014-01-01

    Objective: To determine the occurrence of clinical signs of dysphagia in infants with acute viral bronchiolitis, to compare the respiratory parameters during deglutition, and to ensure the intra- and inter- examiners agreement, as well as to accomplish intra and interexaminators concordance of the clinical evaluation of the deglutition. Methods: This was a cross-sectional study of 42 infants aged 0-12 months. The clinical evaluation was accompanied by measurements of respiratory rate and pulse oximetry. A score of swallowing disorders was designed to establish associations with other studied variables and to ensure the intra- and interrater agreement of clinical feeding assessments. Caregivers also completed a questionnaire about feeding difficulties. Significance was set at p<0.05. Results: Changes in the oral phase (prolonged pauses) and pharyngeal phase (wheezing, coughing and gagging) of swallowing were found. A significant increase in respiratory rate between pre- and post-feeding times was found, and it was determined that almost half of the infants had tachypnea. An association was observed between the swallowing disorder scores and a decrease in oxygen saturation. Infants whose caregivers reported feeding difficulties during hospitalization stated a significantly greater number of changes in the swallowing evaluation. The intra-rater agreement was considered to be very good. Conclusions: Infants with acute viral bronchiolitis displayed swallowing disorders in addition to changes in respiratory rate and measures of oxygen saturation. It is suggested, therefore, that infants displaying these risk factors have a higher probability of dysphagia. PMID:25479843

  14. Immunosuppressive drug therapy for preventing rejection following lung transplantation in cystic fibrosis.

    PubMed

    Saldanha, Ian J; Akinyede, Oluwaseun; Robinson, Karen A

    2018-06-18

    For people with cystic fibrosis and advanced pulmonary damage, lung transplantation is an available and viable option. However, graft rejection is an important potential consequence after lung transplantation. Immunosuppressive therapy is needed to prevent episodes of graft rejection and thus subsequently reduce morbidity and mortality in this population. There are a number of classes of immunosuppressive drugs which act on different components of the immune system. There is considerable variability in the use of immunosuppressive agents after lung transplantation in cystic fibrosis. While much of the research in immunosuppressive drug therapy has focused on the general population of lung transplant recipients, little is known about the comparative effectiveness and safety of these agents in people with cystic fibrosis. This is an update of a previously published review. To assess the effects of individual drugs or combinations of drugs compared to placebo or other individual drugs or combinations of drugs in preventing rejection following lung transplantation in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the potentially eligible study. We also searched the www.clinicaltrials.gov registry and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP) to obtain information on unpublished and ongoing studies.Date of latest search: 29 May 2018. Randomised and quasi-randomised studies. We independently assessed the studies identified from our searches for inclusion in the review. Should eligible studies be identified and included in future updates of the review, we will independently extract data and assess the risk of bias. We will use GRADE to summarize our results through a summary of findings table for each comparison we present in the review. While five studies addressed the interventions of interest, we did not include them in the

  15. 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. © 2016 Steunstichting ESOT.

  16. Differential diagnosis of acute rejection and chronic cyclosporine nephropathy after rat renal transplantation by detection of endothelial microparticles (EMP).

    PubMed

    Cui, Jiewei; Yang, Jing; Cao, Weike; Sun, Yi

    2010-12-01

    Endothelial microparticles (EMP) are small vesicles smaller than 1.0μm, released from endothelial cells (EC) during their activation and (or) apoptosis. The assay of the level of elevated EMP is a new approach to evaluate the dysfunction of endothelial cell. EMP can be classified into several types according to their membrane molecular, and the levels of various types of EMP may be different. As the most cost-effective immunodepressant, cyclosporine A (CsA) has been used widely in organ transplantation. But its dose is hard to control, under-medication may cause the acute rejection (AR) and overdose may cause chronic cyclosporine nephropathy (CCN). The cyclosporine A (CsA) caused CCN and the AR caused renal injury after renal transplantation are both vascular diseases related with endothelial dysfunction, and up to now, there is still no effective method to distinguish the two kinds of diseases. Owing to distinct pathogenesis of the two kinds of vascular diseases, the level of each type of EMP originated from vascular endothelial cells may be different. We hypothesize that maybe we can distinguish them by detecting the different levels of some types of EMP which is also related with vascular disease, and we propose to prove our hypothesis through animal experiment. If our hypothesis is proved, it will be more helpful for clinicians to adjust the dose of CsA promptly according to the differential diagnosis of the two kinds of diseases. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Insulin resistance and clinical outcomes after acute ischemic stroke.

    PubMed

    Ago, Tetsuro; Matsuo, Ryu; Hata, Jun; Wakisaka, Yoshinobu; Kuroda, Junya; Kitazono, Takanari; Kamouchi, Masahiro

    2018-04-24

    In this study, we aimed to determine whether insulin resistance is associated with clinical outcomes after acute ischemic stroke. We enrolled 4,655 patients with acute ischemic stroke (aged 70.3 ± 12.5 years, 63.5% men) who had been independent before admission; were hospitalized in 7 stroke centers in Fukuoka, Japan, from April 2009 to March 2015; and received no insulin therapy during hospitalization. The homeostasis model assessment of insulin resistance (HOMA-IR) score was calculated using fasting blood glucose and insulin levels measured 8.3 ± 7.8 days after onset. Study outcomes were neurologic improvement (≥4-point decrease in NIH Stroke Scale score or 0 at discharge), poor functional outcome (modified Rankin Scale score of ≥3 at 3 months), and 3-month prognosis (stroke recurrence and all-cause mortality). Logistic regression analysis was used to evaluate the association of the HOMA-IR score with clinical outcomes. The HOMA-IR score was associated with neurologic improvement (odds ratio, 0.68 [95% confidence interval, 0.56-0.83], top vs bottom quintile) and with poor functional outcome (2.02 [1.52-2.68], top vs bottom quintile) after adjusting for potential confounding factors, including diabetes and body mass index. HOMA-IR was not associated with stroke recurrence or mortality within 3 months of onset. The associations were maintained in nondiabetic or nonobese patients. No heterogeneity was observed according to age, sex, stroke subtype, or stroke severity. These findings suggest that insulin resistance is independently associated with poor functional outcome after acute ischemic stroke apart from the risk of short-term stroke recurrence or mortality. © 2018 American Academy of Neurology.

  18. Clinical experience with induction therapy in renal transplantation.

    PubMed

    Muntean, Adriana; Lucan, Mihai; Barbos, Adrian; Elec, Alina; Iacob, Gheorghita; Loga, Luminita; Dican, Lucia

    2013-01-01

    Acute rejection (AR) is a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains the improvement seen in the results of transplantation in recent years. To assess the optimal immunosuppression regimen according to the immunological risk of renal transplant patients. We performed a retrospective study of 977 consecutive patients transplanted in our institution between January 2000 and December 2011. Recipients were classified according to the immunological risk (high, intermediate and low) and the type of induction therapy received. We evaluated the incidence of early acute rejection (eAR) and late acute rejection (lAR) and their influence on graft and patients survival in relation to the immunological risk and induction regimen used. The incidence of eAR was 5.4%, 6.4% and 1.4% in relation with the immunological risk, high, intermediate and low respectively. The most commonly used induction immunosuppression was rabbit antithymocyte globulin (ATG), followed by methylprednisolone and basiliximab. No statistical difference was found between the incidence of eAR according to the type of induction therapy and immunological risk. The graft survival was significantly better for the cases without eAR at 1 year (98.6% versus 94.4%, p=0.019), and 3 years (94.9% versus 88.9%, p=0.056). The patients survival was significantly better for those without eAR at 1 year after transplant (95.7% vs. 88.9%, p=0.051), 3 years (93.1% vs. 83.3%, p=0.008) and 5 years (92.2% vs. 79.6%, p=0.001). The incidence of lAR was between 0 and 7.1% according to the induction therapy, lacking any statistical significance (p=0.450). Tailoring the induction immunosuppression according to the immunological risk reduces the incidence of early acute rejection.

  19. Clinical experience with induction therapy in renal transplantation

    PubMed Central

    MUNTEAN, ADRIANA; LUCAN, MIHAI; BARBOS, ADRIAN; ELEC, ALINA; IACOB, GHEORGHITA; LOGA, LUMINITA; DICAN, LUCIA

    2013-01-01

    Introduction Acute rejection (AR) is a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains the improvement seen in the results of transplantation in recent years. Objective To assess the optimal immunosuppression regimen according to the immunological risk of renal transplant patients. Method We performed a retrospective study of 977 consecutive patients transplanted in our institution between January 2000 and December 2011. Recipients were classified according to the immunological risk (high, intermediate and low) and the type of induction therapy received. We evaluated the incidence of early acute rejection (eAR) and late acute rejection (lAR) and their influence on graft and patients survival in relation to the immunological risk and induction regimen used. Results The incidence of eAR was 5.4%, 6.4% and 1.4% in relation with the immunological risk, high, intermediate and low respectively. The most commonly used induction immunosuppression was rabbit antithymocyte globulin (ATG), followed by methylprednisolone and basiliximab. No statistical difference was found between the incidence of eAR according to the type of induction therapy and immunological risk. The graft survival was significantly better for the cases without eAR at 1 year (98.6% versus 94.4%, p=0.019), and 3 years (94.9% versus 88.9%, p=0.056). The patients survival was significantly better for those without eAR at 1 year after transplant (95.7% vs. 88.9%, p=0.051), 3 years (93.1% vs. 83.3%, p=0.008) and 5 years (92.2% vs. 79.6%, p=0.001). The incidence of lAR was between 0 and 7.1% according to the induction therapy, lacking any statistical significance (p=0.450). Conclusion Tailoring the induction immunosuppression according to the immunological risk reduces the incidence of early acute rejection. PMID:26527980

  20. Cytokines in the regulation of allograft rejection.

    PubMed

    Huber, C; Irschick, E

    1988-01-01

    Stimulation of T lymphocytes with alloantigen leads to release of both IL-2 and IFN-gamma. IL-2 enhances clonal expansion of alloantigen-activated T cells. This permits it to overcome acquired allograft tolerance which, at the efferent limb of the cellular immune response, is caused by reduced clone size of donor-specific cytotoxic lymphocyte precursor cells. Cells exhibiting a low constitutive expression of class I MHC antigenes are refractory to lysis by cytotoxic T cells. This second type of tolerance located at the level of the allogeneic target cells can be easily broken by exogenous IFN-gamma, which increases the density of class I MHC antigens. There is suggestive evidence for enhanced endogenous production of lymphokines during rejection of cardiac allografts in mice and men. Rejection episodes are also associated with increased expression of class I and elevated frequency of class II MHC antigen-positive cells in the cardiac transplants. Whereas early immune recognition of histoincompatible grafts is primarily related to the presence of genetic barriers between donor and recipient, the further amplification of alloreactivity is driven by the release of antigen-unspecific lymphokines. Production of endogenous lymphokines can be modified by a variety of means: methylprednisone, ciclosporin and specific antibodies against lymphokines or their receptors represent effective inhibitors of this amplification mechanism which can finally lead to irreversible graft damage. It is well established in clinical experience that infectious complications subsequent to allografting may precipitate rejection or graft-vs.-host disease. Our finding of increased endogenous IFN-gamma levels during infections, in particular in those caused by cytomegalovirus, provides an explanation for this association.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Clinical correlates of acute pulmonary events in children and adolescents with sickle cell disease*

    PubMed Central

    Paul, Rabindra; Minniti, Caterina P.; Nouraie, Mehdi; Luchtman-Jones, Lori; Campbell, Andrew; Rana, Sohail; Onyekwere, Onyinye; Darbari, Deepika S.; Ajayi, Olaid; Arteta, Manuel; Ensing, Gregory; Sable, Craig; Dham, Niti; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Gordeuk, Victor R.

    2013-01-01

    Objectives We aimed to identify risk factors for acute pulmonary events in children and adolescents in the Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study. Methods Patients with hemoglobin SS (n=376) and other sickle cell genotypes (n=127) aged 3-20 years were studied at four centers in a cross-sectional manner. A sub-group (n=293) was followed for a median of 21 months (range 9-35). Results A patient-reported history of one or more acute pulmonary events, either acute chest syndrome (ACS) or pneumonia, was obtained in 195 hemoglobin SS patients (52%) and 51 patients with other genotypes (40%). By logistic regression, history of acute pulmonary events was independently associated with patient-reported history of asthma (p<0.0001), older age (p=0.001), >3 severe pain episodes in the preceding 12 months (p=0.002), higher tricuspid regurgitation velocity (TRV) (p=0.028), and higher white blood cell (WBC) count (p=0.043) among hemoglobin SS patients. History of acute pulmonary events was associated with >3 severe pain episodes (p=0.009) among patients with other genotypes. During follow-up, 43 patients (15%) had at least one new ACS episode including 11 without a baseline history of acute pulmonary events. History of acute pulmonary events (odds ratio 5.4; p<0.0001) and younger age (odds ratio 0.9; p=0.010) were independently associated with developing a new episode during follow-up. Conclusions Asthma history, frequent pain and higher values for TRV and WBC count were independently associated with history of acute pulmonary events in hemoglobin SS patients and frequent pain was associated in those with other genotypes. Measures to reduce pain episodes and control asthma may help to decrease the incidence of acute pulmonary events in SCD. PMID:23560516

  2. Study protocol of cost-effectiveness and cost-utility of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial

    PubMed Central

    2011-01-01

    Background Low back pain (LBP), with high incidence and prevalence rate, is one of the most common reasons to consult the health system and is responsible for a significant amount of sick leave, leading to high health and social costs. The objective of the study is to assess the cost-effectiveness and cost-utility analysis of a multidisciplinary biopsychosocial educational group intervention (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the working population recruited in primary healthcare centres. Methods/design The study design is a cost-effectiveness and cost-utility analysis of a MBEGI in comparison with the usual care of non-specific sub-acute LBP. Measures on effectiveness and costs of both interventions will be obtained from a cluster randomised controlled clinical trial carried out in 38 Catalan primary health care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical treatments, work sick leave (% and duration in days), Roland Morris disability, McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires. Utility measures will be calculated from the SF-12. The analysis will be performed from a social perspective. The temporal horizon is at 3 months (change to chronic LBP) and 12 months (evaluate the outcomes at long term). Assessment of outcomes will be blinded and will follow the intention-to-treat principle. Discussion We hope to demonstrate the cost-effectiveness and cost-utility of MBEGI, see an improvement in the patients' quality of life, achieve a reduction in the duration of episodes and the chronicity of non-specific low back pain, and be able to report a decrease in the social costs. If the intervention is cost-effectiveness and cost-utility, it could be applied to Primary Health Care Centres. Trial registration ISRCTN: ISRCTN58719694 PMID:21859489

  3. Understanding maladaptive responses to rejection: Aggression with an audience.

    PubMed

    DeBono, Amber; Layton, Rebekah L; Freeman, Nicholas; Muraven, Mark

    2017-01-01

    Logically, responding aggressively to rejection is maladaptive because one is unlikely to seek a relationship with an aggressor. We predict that when concealed, the illogical aggressive response to rejection is more likely, whereas when the rejected individuals' aggressive responses are perceived as public, the aggressive acts may be reduced. Participants were rejected by others (Experiment 1) or were either accepted or rejected during an online ball-tossing game (Experiment 2) and were then given an opportunity to aggress publicly or privately. Across experiments, when the opportunity to aggress was made public, rejected participants exhibited less aggressive behavior. When concerned about the perception of their public aggressive responses by others, rejected individuals' aggressive responses diminished compared with those whose actions were private. Crucially, this extended to aggression visible only to neutral others, suggesting that effects cannot solely be due to fear of retribution.

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

    PubMed

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

    2004-12-01

    Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174-5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/group) and one group with anti-VAP-1 2 mg/kg daily (n = 7). On day 7, samples were collected for transplant aspiration cytology, histology, and immunohistochemistry. Lymphocyte infiltration to the graft was clearly affected by VAP-blockade. The total inflammation, mainly the number of active lymphoid cells, in transplant aspiration cytology was significantly decreased in animals treated with anti-VAP-1 (4.7 +/- 1.0 and 2.4 +/- 1.0 corrected increment units, respectively) compared to control (6.6 +/- 1.0) (P < 0.05). In histology, the intensity of portal inflammation was significantly decreased (P < 0.05). The amount of T cells expressing activation markers diminished. This is the first demonstration in any prolonged in vivo model that VAP-1 plays an important role in lymphocyte infiltration to sites of inflammation, and, in particular, liver allograft rejection.

  5. Parental Acceptance-Rejection Theory and the Phylogenetic Model.

    ERIC Educational Resources Information Center

    Rohner, Ronald P.

    Guided by specific theoretical and methodological points of view--the phylogenetic perspective and the universalistic approach respectively--this paper reports on a worldwide study of the antecedents and effects of parental acceptance and rejection. Parental acceptance-rejection theory postulates that rejected children throughout our species share…

  6. Acute right lower abdominal pain in women of reproductive age: Clinical clues

    PubMed Central

    Hatipoglu, Sinan; Hatipoglu, Filiz; Abdullayev, Ruslan

    2014-01-01

    AIM: To study possible gynecological organ pathologies in the differential diagnosis of acute right lower abdominal pain in patients of reproductive age. METHODS: Following Clinical Trials Ethical Committee approval, the retrospective data consisting of physical examination and laboratory findings in 290 patients with sudden onset right lower abdominal pain who used the emergency surgery service between April 2009 and September 2013, and underwent surgery and general anesthesia with a diagnosis of acute appendicitis were collated. RESULTS: Total data on 290 patients were obtained. Two hundred and twenty-four (77.2%) patients had acute appendicitis, whereas 29 (10%) had perforated appendicitis and 37 (12.8%) had gynecological organ pathologies. Of the latter, 21 (7.2%) had ovarian cyst rupture, 12 (4.2%) had corpus hemorrhagicum cyst rupture and 4 (1.4%) had adnexal torsion. Defense, Rovsing’s sign, increased body temperature and increased leukocyte count were found to be statistically significant in the differential diagnosis of acute appendicitis and gynecological organ pathologies. CONCLUSION: Gynecological pathologies in women of reproductive age are misleading in the diagnosis of acute appendicitis. PMID:24744594

  7. The Neural Basis of Recollection Rejection: Increases in Hippocampal-Prefrontal Connectivity in the Absence of a Shared Recall-to-Reject and Target Recollection Network.

    PubMed

    Bowman, Caitlin R; Dennis, Nancy A

    2016-08-01

    Recollection rejection or "recall-to-reject" is a mechanism that has been posited to help maintain accurate memory by preventing the occurrence of false memories. Recollection rejection occurs when the presentation of a new item during recognition triggers recall of an associated target, a mismatch in features between the new and old items is registered, and the lure is correctly rejected. Critically, this characterization of recollection rejection involves a recall signal that is conceptually similar to recollection as elicited by a target. However, previous neuroimaging studies have not evaluated the extent to which recollection rejection and target recollection rely on a common neural signal but have instead focused on recollection rejection as a postretrieval monitoring process. This study utilized a false memory paradigm in conjunction with an adapted remember-know-new response paradigm that separated "new" responses based on recollection rejection from those that were based on a lack of familiarity with the item. This procedure allowed for parallel recollection rejection and target recollection contrasts to be computed. Results revealed that, contrary to predictions from theoretical and behavioral literature, there was virtually no evidence of a common retrieval mechanism supporting recollection rejection and target recollection. Instead of the typical target recollection network, recollection rejection recruited a network of lateral prefrontal and bilateral parietal regions that is consistent with the retrieval monitoring network identified in previous neuroimaging studies of recollection rejection. However, a functional connectivity analysis revealed a component of the frontoparietal rejection network that showed increased coupling with the right hippocampus during recollection rejection responses. As such, we demonstrate a possible link between PFC monitoring network and basic retrieval mechanisms within the hippocampus that was not revealed with

  8. `An observational report of intensive robotic and manual gait training in sub-acute stroke

    PubMed Central

    2012-01-01

    Background The use of automated electromechanical devices for gait training in neurological patients is increasing, yet the functional outcomes of well-defined training programs using these devices and the characteristics of patients that would most benefit are seldom reported in the literature. In an observational study of functional outcomes, we aimed to provide a benchmark for expected change in gait function in early stroke patients, from an intensive inpatient rehabilitation program including both robotic and manual gait training. Methods We followed 103 sub-acute stroke patients who met the clinical inclusion criteria for Body Weight Supported Robotic Gait Training (BWSRGT). Patients completed an intensive 8-week gait-training program comprising robotic gait training (weeks 0-4) followed by manual gait training (weeks 4-8). A change in clinical function was determined by the following assessments taken at 0, 4 and 8 weeks (baseline, mid-point and end-point respectively): Functional Ambulatory Categories (FAC), 10 m Walking Test (10 MWT), and Tinetti Gait and Balance Scales. Results Over half of the patients made a clinically meaningful improvement on the Tinetti Gait Scale (> 3 points) and Tinetti Balance Scale (> 5 points), while over 80% of the patients increased at least 1 point on the FAC scale (0-5) and improved walking speed by more than 0.2 m/s. Patients responded positively in gait function regardless of variables gender, age, aetiology (hemorrhagic/ischemic), and affected hemisphere. The most robust and significant change was observed for patients in the FAC categories two and three. The therapy was well tolerated and no patients withdrew for factors related to the type or intensity of training. Conclusions Eight-weeks of intensive rehabilitation including robotic and manual gait training was well tolerated by early stroke patients, and was associated with significant gains in function. Patients with mid-level gait dysfunction showed the most robust

  9. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is rejected...

  10. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is rejected...

  11. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is rejected...

  12. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is rejected...

  13. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is rejected...

  14. Prevalence and characteristics of foal rejection in Arabian mares.

    PubMed

    Juarbe-Díaz, S V; Houpt, K A; Kusunose, R

    1998-09-01

    Separate surveys of Thoroughbred, Paint, and Arabian mare owners revealed a higher than expected rate of foal rejection in Arabian mares. A behavioural history form was submitted by owners of foal rejecting and nonrejecting Arabian mares, and maternal behaviour and management practices compared. Four generation pedigrees of rejecting and nonrejecting Arabian mares were also examined. Foal rejecting mares were more likely to avoid, threaten, squeal at, chase, bite, and kick their foals post partum than nonrejecting mares. Nonrejecting mares were more likely to lick, nicker and defend their foals post partum than rejecting mares. No statistically significant relationship was found between foal rejection and the type of breeding method (natural vs. artificial insemination), the presence of people at birth, the presence of nearby horses at birth, or assistance of the first nursing bout. The presence at least once of 1 of 2 related sires was statistically higher in the pedigrees of rejecting vs. nonrejecting mares. Inherited and learned or environmental factors are likely to affect the expression of foal rejection behaviour.

  15. Core Domains for Clinical Research in Acute Respiratory Failure Survivors: An International Modified Delphi Consensus Study.

    PubMed

    Turnbull, Alison E; Sepulveda, Kristin A; Dinglas, Victor D; Chessare, Caroline M; Bingham, Clifton O; Needham, Dale M

    2017-06-01

    To identify the "core domains" (i.e., patient outcomes, health-related conditions, or aspects of health) that relevant stakeholders agree are essential to assess in all clinical research studies evaluating the outcomes of acute respiratory failure survivors after hospital discharge. A two-round consensus process, using a modified Delphi methodology, with participants from 16 countries, including patient and caregiver representatives. Prior to voting, participants were asked to review 1) results from surveys of clinical researchers, acute respiratory failure survivors, and caregivers that rated the importance of 19 preliminary outcome domains and 2) results from a qualitative study of acute respiratory failure survivors' outcomes after hospital discharge, as related to the 19 preliminary outcome domains. Participants also were asked to suggest any additional potential domains for evaluation in the first Delphi survey. Web-based surveys of participants representing four stakeholder groups relevant to clinical research evaluating postdischarge outcomes of acute respiratory failure survivors: clinical researchers, clinicians, patients and caregivers, and U.S. federal research funding organizations. None. None. Survey response rates were 97% and 99% in round 1 and round 2, respectively. There were seven domains that met the a priori consensus criteria to be designated as core domains: physical function, cognition, mental health, survival, pulmonary function, pain, and muscle and/or nerve function. This study generated a consensus-based list of core domains that should be assessed in all clinical research studies evaluating acute respiratory failure survivors after hospital discharge. Identifying appropriate measurement instruments to assess these core domains is an important next step toward developing a set of core outcome measures for this field of research.

  16. Stomaching rejection: Self-compassion and self-esteem moderate the impact of daily social rejection on restrictive eating behaviours among college women.

    PubMed

    Beekman, Janine B; Stock, Michelle L; Howe, George W

    2017-11-01

    The present study examined whether having high self-esteem or a self-compassionate perspective help mitigate the impact of daily social rejection on negative affect and restrictive eating behaviours. Following a baseline survey assessing self-esteem and self-compassion, 121 college women completed online daily diaries for one week. Negative affect and restrictive eating behaviours. On days when women reported more rejection, they also reported higher restrictive eating behaviours and greater negative affect. Effects were moderated by self-esteem and self-compassion, such that the lower participants were in self-esteem or self-compassion, the stronger the positive relation between rejection and negative affect and restrictive eating. However, only the common humanity/isolation dimension of self-compassion significantly moderated daily effects of rejection when controlling for self-esteem. Mediated moderation results reveal different mechanisms by which self-esteem and self-compassion buffer against rejections' effects on affect and restrictive eating. Self-compassion and self-esteem influence the complex impact that social rejection has on affect and restrictive eating. More than other dimensions of self-compassion or self-esteem, remembering one's common humanity can result in a healthier response to social rejection.

  17. Longitudinal Associations between Parental Rejection and Bullying/Victimization

    ERIC Educational Resources Information Center

    Stavrinides, Panayiotis; Tantaros, Spyridon; Georgiou, Stelios; Tricha, Loukia

    2018-01-01

    The present study investigated the direction of the relationship between parental rejection and children's engagement in bullying and victimization. Using a cross-lagged design, we examined whether (a) bullying and victimization predict an increase in parental rejection six months later, (b) parental rejection predicts an increase in bullying and…

  18. Symptoms, functioning and quality of life after treatment in a residential sub-acute mental health service in Australia.

    PubMed

    Thomas, Kerry A; Rickwood, Debra J; Brown, Patricia M

    2017-01-01

    The aim of this study was to assess clients' and service providers' perspectives on changes in mental health after an admission to a residential recovery-focused, sub-acute service, in Australia. Clients were either step-up clients, entering the service directly from the community, or step-down clients who were transitioning from an inpatient unit to home. During the 30-month period of data collection (August 2011 to January 2014) all clients (N = 102) were invited to participate in the longitudinal study and 41 clients consented to be involved (38% response rate). At admission and exit, participants completed the Behaviour and Symptom Identification Scale (Basis-32) and service providers completed the Life Skills Profile-16 and Health of the Nations Outcome Scales. Follow-up data 3 months after exit were available for 12 clients, including the Basis-32 and a self-report measure of quality of life (Assessment of Quality of Life 8-dimension). Both client groups reported positive improvements between admission and exit in the areas of relation to self and others, psychosis, daily living and presence of depression or anxiety symptoms. Service providers reported gains for clients in the areas of self-care, level of symptoms and presence of social problems. At 3 months, clients generally reported positive quality of life, although there was no significant change in symptoms and functioning. This study demonstrates that after an admission to a sub-acute service, step-up clients experience an improvement in their symptoms and functioning, have avoided a hospital admission and are well enough to return home. Step-down clients also experience further improvements in their symptoms and functioning, indicating that the service has assisted them in their transition to independent living after a hospital admission. Sub-acute residential units provide a continuation of care for inpatients preparing to return home, and people with a mental health problem living in the

  19. Modular Ankle Robotics Training in Early Sub-Acute Stroke: A Randomized Controlled Pilot Study

    PubMed Central

    Forrester, Larry W.; Roy, Anindo; Krywonis, Amanda; Kehs, Glenn; Krebs, Hermano Igo; Macko, Richard F.

    2014-01-01

    Background Modular lower extremity (LE) robotics may offer a valuable avenue for restoring neuromotor control after hemiparetic stroke. Prior studies show that visually-guided and visually-evoked practice with an ankle robot (anklebot) improves paretic ankle motor control that translates into improved overground walking. Objective Assess the feasibility and efficacy of daily anklebot training during early sub-acute hospitalization post-stroke. Methods Thirty-four inpatients from a stroke unit were randomly assigned to anklebot (N=18) or passive manual stretching (N=16) treatments. All suffered a first stroke with residual hemiparesis (ankle manual muscle test grade 1/5 to 4/5), and at least trace muscle activation in plantar- or dorsiflexion. Anklebot training employed an “assist-as-needed” approach during > 200 volitional targeted paretic ankle movements, with difficulty adjusted to active range of motion and success rate. Stretching included >200 daily mobilizations in these same ranges. All sessions lasted 1 hour and assessments were not blinded. Results Both groups walked faster at discharge, however the robot group improved more in percent change of temporal symmetry (p=0.032) and also of step length symmetry (p=0.038), with longer nonparetic step lengths in the robot (133%) vs. stretching (31%) groups. Paretic ankle control improved in the robot group, with increased peak (p≤ 0.001) and mean (p≤ 0.01) angular speeds, and increased movement smoothness (p≤ 0.01). There were no adverse events. Conclusion Though limited by small sample size and restricted entry criteria, our findings suggest that modular lower extremity robotics during early sub-acute hospitalization is well tolerated and improves ankle motor control and gait patterning. PMID:24515923

  20. Clinical Study on Acute Pancreatitis in Pregnancy in 26 Cases

    PubMed Central

    Qihui, Cheng; Xiping, Zhang; Xianfeng, Ding

    2012-01-01

    Aim. This paper investigated the pathogenesis and treatment strategies of acute pancreatitis (AP) in pregnancy. Methods. We analyzed retrospectively the characteristics, auxiliary diagnosis, treatment strategies, and clinical outcomes of 26 cases of patients with AP in pregnancy. Results. All patients were cured finally. (1) Nine cases of 22 mild acute pancreatitis (MAP) patients selected automatic termination of pregnancy because of the unsatisfied therapeutic efficacy or those patients' requirements. (2) Four cases of all patients were complicated with severe acute pancreatitis (SAP); 2 cases underwent uterine incision delivery while one of them also received cholecystectomy, debridement and drainage of pancreatic necrosis, and percutaneous jejunostomy. One case had a fetal death when complicated with SAP; she had to receive extraction of bile duct stones and drainage of abdominal cavity after induced abortion. The other one case with hyperlipidemic pancreatitis was given induced abortion and hemofiltration. Conclusions. The first choice of MAP in pregnancy is the conventional therapy. Apart from the conventional therapy, we need to terminate pregnancy as early as possible for patients with SAP. Removing biliary calculi and drainage is supposed to be considered for acute biliary pancreatitis. Lowering blood lipids treatment should be applied to hyperlipidemic pancreatitis or given to hemofiltration when necessary. PMID:23213326

  1. Renal Histopathologic Findings Associated With Severity of Clinical Acute Kidney Injury.

    PubMed

    Kudose, Satoru; Hoshi, Masato; Jain, Sanjay; Gaut, Joseph P

    2018-05-01

    Acute kidney injury (AKI) is a significant cause of morbidity and mortality. Acute tubular injury is considered to be the early pathologic manifestation of AKI, however, the underlying pathology is complex, lacks standards for interpretation, and its relationship with AKI often is unclear or inconsistent. To clarify clinicopathologic correlations in AKI, we evaluated 32 histologic findings in 100 kidney biopsies from patients with AKI as a training set to correlate pathologic findings with clinical AKI grades. Kidney Injury Molecule-1 quantitative immunohistochemistry was performed to confirm tubular injury. A separate cohort of 50 biopsies were evaluated blinded to clinical information to validate the findings. Pathologic tubular injury correlated best with Kidney Disease Improving Global Outcomes criteria. Tubular epithelial simplification, tubular epithelial mitosis, and cell sloughing correlated well with clinically severe AKI and were used to construct a tubular injury classification scheme with sensitivity of 0.93 (0.85, 1), specificity of 0.95 (0.83, 1), and area under the receiver-operating characteristic curve of 0.98 (0.98, 1) for grades 2 to 3 AKI. Predictive ability of the model did not improve when Kidney Injury Molecule-1 immunostaining results were added. The results show a strong correlation between pathologic tubular injury and modern clinical definitions of AKI. The proposed classification scheme may aid in development of more precise and clinically meaningful interpretations of pathologic tubular injury in native kidney biopsies and provides simple pathologic criteria without special studies that can easily be adopted globally.

  2. Agreement in Mother and Father Acceptance-Rejection, Warmth, and Hostility/Rejection/Neglect of Children across Nine Countries

    PubMed Central

    Putnick, Diane L.; Bornstein, Marc H.; Lansford, Jennifer E.; Chang, Lei; Deater-Deckard, Kirby; Di Giunta, Laura; Gurdal, Sevtap; Dodge, Kenneth A.; Malone, Patrick S.; Oburu, Paul; Pastorelli, Concetta; Skinner, Ann T.; Sorbring, Emma; Tapanya, Sombat; Uribe Tirado, Liliana Maria; Zelli, Arnaldo; Alampay, Liane Peña; Al-Hassan, Suha M.; Bacchini, Dario; Bombi, Anna Silvia

    2011-01-01

    We assessed whether mothers’ and fathers’ self-reports of acceptance-rejection, warmth, and hostility/rejection/neglect (HRN) of their pre-adolescent children differ cross-nationally and relative to the gender of the parent and child in 10 communities in 9 countries, including China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States (N = 998 families). Mothers and fathers in all countries reported a high degree of acceptance and warmth, and a low degree of HRN, but countries also varied. Mothers reported greater acceptance of children than fathers in China, Italy, Sweden, and the United States, and these effects were accounted for by greater self-reported warmth in mothers than fathers in China, Italy, the Philippines, Sweden, and Thailand and less HRN in mothers than fathers in Sweden. Fathers reported greater warmth than mothers in Kenya. Mother and father acceptance-rejection were moderately correlated. Relative levels of mother and father acceptance and rejection appear to be country specific. PMID:23024576

  3. Prevention and treatment of corneal graft rejection: current practice patterns of the Cornea Society (2011).

    PubMed

    Kharod-Dholakia, Bhairavi; Randleman, J Bradley; Bromley, Jennifer G; Stulting, R Doyle

    2015-06-01

    To analyze current practice patterns in the prevention and treatment of corneal graft rejection for both penetrating keratoplasty (PK) and endothelial keratoplasty (EK) and to compare these patterns with previously reported practices. In 2011, an electronic survey was sent to 670 members of the Cornea Society worldwide addressing the routine postoperative management of corneal transplants at different time points, treatment of various manifestations of corneal graft rejection, and preferred surgical techniques. A total of 204 of 670 surveys (30%) were returned and evaluated. All respondents used topical corticosteroids for routine postoperative management and treatment of endothelial graft rejection. Prednisolone was the topical steroid of choice in all clinical scenarios, similar to previous surveys from 1989 to 2004. Use of subconjunctival and systemic steroids increased for many scenarios of probable and definite graft rejection. Routine use of prednisolone decreased by approximately 10% from previous surveys, whereas difluprednate was used in 13% of high-risk eyes during the first 6 months. Dexamethasone, fluorometholone, and loteprednol use remained stable. Adjunctive topical cyclosporine use increased significantly for PK and EK. EK was the preferred technique for endothelial dysfunction, whereas PK and deep anterior lamellar keratoplasty were both used for keratoconus and anterior scars. Most respondents (75%) felt that graft rejection occurs more frequently after PK than after EK. Prednisolone remains the treatment of choice for management and treatment of graft rejection; however, since the introduction of difluprednate, its use has declined slightly since the introduction of difluprednate. Despite perceived differences in rejection rates, there were no differences in prophylactic steroid treatment for PK and EK.

  4. Laughter as a social rejection cue: Influence of prior explicit experience of social rejection on cardiac signs of "freezing".

    PubMed

    Lackner, Helmut K; Reiter-Scheidl, Katharina; Aydin, Nilüfer; Perchtold, Corinna M; Weiss, Elisabeth M; Papousek, Ilona

    2018-06-01

    The study aimed at investigating the immediate cardiac effect of the sudden perception of other people's laughter after experimentally manipulating healthy participants' proneness to experience laughter as a cue of social threat. We expected that participants would show cardiac signs of freezing (i.e., sustained heart rate deceleration immediately after perception of the laughter) after prior social rejection but not or less so after prior acceptance, due to an increased bias to perceive the ambiguous social signal as a cue of social threat and rejection after rejection had been primed. Contrary to expectations, the perception of other people's laughter elicited a decelerative (freezing) response regardless of whether it was preceded by the experience of social rejection or acceptance. The response was prolonged in participants who had been accepted beforehand compared to those who had been rejected. The findings indicate that, given a relevant social context, other people's laughter can be a powerful cue of social threat and rejection also in healthy individuals. Prolonged heart rate deceleration after an ambiguous social signal may facilitate the processing of significant social information in the socially threatening situation. The study adds to the literature rendering the course of the immediate transient heart rate response a useful tool in social rejection research. Additionally, the findings suggested that in some cases the further progress of transient heart rate changes in more extended time-windows (about 30 s) may provide additional relevant information about the processing of social cues. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. [Study on clinical effectiveness of acupuncture and moxibustion on acute Bell's facial paralysis: randomized controlled clinical observation].

    PubMed

    Wu, Bin; Li, Ning; Liu, Yi; Huang, Chang-qiong; Zhang, Yong-ling

    2006-03-01

    To investigate the adverse effects of acupuncture on the prognosis, and effectiveness of acupuncture combined with far infrared ray in the patient of acute Bell's facial paralysis within 48 h. Clinically randomized controlled trial was used, and the patients were divided into 3 groups: group A (early acupuncture group), group B (acupuncture combined with far infrared ray) and group C (acupuncture after 7 days). The facial nerve functional classification at the attack, 7 days after the attack and after treatment, the clinically cured rate of following-up of 6 months, and the average cured time, the cured time of complete facial paralysis were observed in the 3 groups. There were no significant differences among the 3 groups in the facial nerve functional classification 7 days after the attack, the clinically cured rate of following-up of 6 months and the average cured time (P > 0.05), but the cured time of complete facial paralysis in the group A and the group B were shorter than that in the group C (P < 0.05). The patient of acute Bell's facial paralysis can be treated with acupuncture and moxibustion, and traditional moxibustion can be replaced by far infrared way.

  6. Urine biomarkers informative of human kidney allograft rejection and tolerance.

    PubMed

    Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

    2018-05-01

    We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

  7. New approaches to the prevention of organ allograft rejection and tolerance induction.

    PubMed

    Bagley, Jessamyn; Tian, Chaorui; Iacomini, John

    2007-07-15

    The therapeutic use of organ allograft transplantation is dependent on the discovery and clinical application of immunologic strategies to blunt the immune response and prevent graft rejection. It was the discovery of powerful immunotherapeutics such as cyclosporine A and rapamycin that has allowed for the widespread use of organ transplantation to treat organ failure. However, despite the attainment of impressive survival rates 1 year after organ transplantation, a significant number of organ allografts are lost to immune-mediated chronic rejection. Furthermore, significant morbidity and mortality can be associated with the use of currently available immunosuppressive regimens. Thus, the development of novel approaches to prevent of organ allograft rejection remains extremely important. Here we discuss two promising and novel avenues of research. First, the discovery and characterization of naturally occurring immune inhibitory signals have led to recent research aimed at exploiting these pathways to induce peripheral tolerance to alloantigen. Furthermore, we discuss new approaches to the induction of donor-specific tolerance by induction of molecular chimerism and the transfer of alloantigen-expressing mature T cells.

  8. High-testosterone men reject low ultimatum game offers.

    PubMed

    Burnham, Terence C

    2007-09-22

    The ultimatum game is a simple negotiation with the interesting property that people frequently reject offers of 'free' money. These rejections contradict the standard view of economic rationality. This divergence between economic theory and human behaviour is important and has no broadly accepted cause. This study examines the relationship between ultimatum game rejections and testosterone. In a variety of species, testosterone is associated with male seeking dominance. If low ultimatum game offers are interpreted as challenges, then high-testosterone men may be more likely to reject such offers. In this experiment, men who reject low offers ($5 out of $40) have significantly higher testosterone levels than those who accept. In addition, high testosterone levels are associated with higher ultimatum game offers, but this second finding is not statistically significant.

  9. Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

    PubMed

    Eapen, Alex K; de Cock, Peter; Crincoli, Christine M; Means, Charlotte; Wismer, Tina; Pappas, Christopher

    2017-07-01

    Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 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 months...

  11. Phenotypes of antibody-mediated rejection in organ transplants.

    PubMed

    Mengel, Michael; Husain, Sufia; Hidalgo, Luis; Sis, Banu

    2012-06-01

    Antibody-mediated hyperacute rejection was the first rejection phenotype observed in human organ transplants. This devastating phenotype was eliminated by reliable crossmatch technologies. Since then, the focus was on T-cell-mediated rejection and de novo donor-specific antibodies were considered an epiphenomenon of cognate T-cell activation. The immune theory was that controlling the T-cell response would entail elimination of antibody-mediated rejection (ABMR). With modern immunosuppressive drugs, T-cell-mediated rejection is essentially treatable. However, this did not prevent ABMR from emerging as a significant phenotype in all types of organ transplants. It became obvious that both rejection types require distinct treatment and thus reliable diagnosis. This is the current challenge. ABMR, depending on stage, grade, time course, organ type or prior treatment, can present with a wide spectrum of phenotypes. This review summarizes the current diagnostic consensus for ABMR, describes unmet needs and challenges in diagnostics, and proposes new approaches for consideration. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

  12. [Clinical signs of dysphagia in infants with acute viral bronchiolitis].

    PubMed

    Barbosa, Lisiane De Rosa; Gomes, Erissandra; Fischer, Gilberto Bueno

    2014-09-01

    To determine the occurrence of clinical signs of dysphagia in infants with acute viral bronchiolitis, to compare the respiratory parameters during deglutition, and to ensure the intra- and inter- examiners agreement, as well as to accomplish intra and interexaminators concordance of the clinical evaluation of the deglutition. This was a cross-sectional study of 42 infants aged 0-12 months. The clinical evaluation was accompanied by measurements of respiratory rate and pulse oximetry. A score of swallowing disorders was designed to establish associations with other studied variables and to ensure the intra- and interrater agreement of clinical feeding assessments. Caregivers also completed a questionnaire about feeding difficulties. Significance was set at p<0.05. Changes in the oral phase (prolonged pauses) and pharyngeal phase (wheezing, coughing and gagging) of swallowing were found. A significant increase in respiratory rate between pre- and post-feeding times was found, and it was determined that almost half of the infants had tachypnea. An association was observed between the swallowing disorder scores and a decrease in oxygen saturation. Infants whose caregivers reported feeding difficulties during hospitalization stated a significantly greater number of changes in the swallowing evaluation. The intra-rater agreement was considered to be very good. Infants with acute viral bronchiolitis displayed swallowing disorders in addition to changes in respiratory rate and measures of oxygen saturation. It is suggested, therefore, that infants displaying these risk factors have a higher probability of dysphagia. Copyright © 2014 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  13. [Clinical and cytological differences in adult acute lymphatic and acute undifferentiated leukemia].

    PubMed

    Abbrederis, K; Schmalzl, F

    1976-01-01

    The usefulness for clinical purposes of the distinction of acute undifferentiated (AUL) and acute lymphocytic leukemia (ALL) is suggested by the following observations: 1. Maturation from AUL to ALL has not been observed. Transformation of ALL to AUL has been reported i.e. less of cytoplasmic polysaccharides; however this seems rather to be the effect of cytotoxic therapy and not a real change of the cytological type. 2. Significant differences among ALL and AUL can be noted as far as the therapeutic response is concerned: All of the 9 patients with ALL but only 2 out of 9 patients with AUL went into remission. The mean survival of the cases with ALL amounts to 34, that of AUL only to 4 months. Out of the patients with ALL 4 patients are still alive in persistant first remission after 77, 57, 36 and 28 months. 3. ALL occurs most frequently in young adults (mean age of 21 patients: 31.7 years): AUL is more frequent in elderly patients (Mean age of 18 patients: 57.6 years). 4. In our material ALL did never occur consequent to a typical preluekemic stage, which was followed either by myeloblastic, monocytic, erythroleukemic or undifferentiated leukemias.

  14. Recent early clinical drug development for acute kidney injury.

    PubMed

    Gallagher, Kevin M; O'neill, Stephen; Harrison, Ewen M; Ross, James A; Wigmore, Stephen J; Hughes, Jeremy

    2017-02-01

    Despite significant need and historical trials, there are no effective drugs in use for the prevention or treatment of acute kidney injury (AKI). There are several promising agents in early clinical development for AKI and two trials have recently been terminated. There are also exciting new findings in pre-clinical AKI research. There is a need to take stock of current progress in the field to guide future drug development for AKI. Areas covered: The main clinical trial registries, PubMed and pharmaceutical company website searches were used to extract the most recent clinical trials for sterile, transplant and sepsis-associated AKI. We summarise the development of the agents recently in clinical trial, update on their trial progress, consider reasons for failed efficacy of two agents, and discuss new paradigms in pre-clinical targets for AKI. Agents covered include- QPI-1002, THR-184, BB-3, heme arginate, human recombinant alkaline phosphatase (recAP), ciclosporin A, AB103, levosimendan, AC607 and ABT-719. Expert opinion: Due to the heterogenous nature of AKI, agents with the widest pleiotropic effects on multiple pathophysiological pathways are likely to be most effective. Linking preclinical models to clinical indication and improving AKI definition and diagnosis are key areas for improvement in future clinical trials.

  15. Randomized Clinical Trial of Intraosseous Methylprednisolone Injection for Acute Pulpitis Pain.

    PubMed

    Bane, Khaly; Charpentier, Emmanuel; Bronnec, François; Descroix, Vianney; Gaye-N'diaye, Fatou; Kane, Abdoul Wahabe; Toledo, Rafael; Machtou, Pierre; Azérad, Jean

    2016-01-01

    The present study reports the results of a randomized clinical trial comparing local intraosseous methylprednisolone injection and emergency pulpotomy in the management of acute pulpitis on efficacy, safety, and efficiency end points. After providing prior informed written consent, 94 patients consulting for acute irreversible pulpitis pain at university-affiliated teaching hospital dental clinics in Dakar, Senegal were randomly assigned to either the methylprednisolone treatment group (n = 47) or the pulpotomy treatment group (n = 47). Patients were followed up at 1 week and assessed 6 months later to evaluate the therapeutic outcome of their treatment. At day 7 the patients in the methylprednisolone group reported less intense spontaneous and percussion pain in the day 0-day 7 period than the patients in the pulpotomy group. Methylprednisolone treatment took approximately 7 minutes (4.6-9.3) less to accomplish than pulpotomy (or about half the time). No difference in the therapeutic outcome was found between the 2 treatment groups at 6 months (all credible intervals span 0). This study establishes that methylprednisolone injection for acute pulpitis is relieved by a minimally invasive pharmacologic approach more effectively than by the reference pulpotomy and conserves scarce dental resources (ie, endodontic equipment and supplies, dental surgeon's time). Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  16. Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Da-Gang

    The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl{sub 4})-induced acute liver injury. Mice were intraperitoneally injected with CCl{sub 4} (0.15 ml/kg). In CCl{sub 4} + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl{sub 4}. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl{sub 4}-induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatmentmore » inhibited CCl{sub 4}-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl{sub 4}-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl{sub 4}-induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl{sub 4}-induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl{sub 4}-induced acute liver injury. These results suggest that OCA protects against CCl{sub 4}-induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl{sub 4}-induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl{sub 4}-induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.« less

  17. [The specific microbiological and clinical features of acute otitis media].

    PubMed

    Gurov, A V; Levina, Yu V; Guseva, A L; Elchueva, Z G; Efimova, S P; Gordienko, M V

    The objective of the present study was to elucidate the specific features of the clinical course of acute otitis media as well as the peculiarities of the vestibular function and the microbial paysage associated with this pathological condition under the present-day conditions. The study included 135 patients presenting with acute otitis media (AOM) at different stages of the disease. The discharge obtained from the tympanic cavity of all the patients was examined with the use of polymerase chain reaction in real time, audiological and vestibulogical methods. The distinctive features of acute otitis medium associated with Streptococcus pneumoniae infection were found to be the intense pain syndrome with the symptoms of intoxication, well apparent inflammatory changes in the tympanic membrane as revealed by otoscopy, the increased frequency of sensorineural impairment of hearing, and the characteristic type B tympanometric curve. Typical of AOM associated with Haemophilus influenza infection are the mild pain syndrome, weak changes in the tympanic membrane as revealed by otoscopy, conductive hearing loss, and the type C tympanometric curve.

  18. Identification of acute self-limited hepatitis B among patients presenting with hepatitis B virus-related acute hepatitis: a hospital-based epidemiological and clinical study.

    PubMed

    Han, Y-N

    2009-01-01

    This study aimed to identify acute self-limited hepatitis B (ASL-HB) among patients presenting with hepatitis B virus (HBV)-related acute hepatitis. Data were available for 220 patients diagnosed with HBV-related acute hepatitis, of whom 164 had acute hepatitis B (AHB). Of these, 160 were confirmed as ASL-HB: three (1.9%) evolved to chronic hepatitis B and one (0.6%) developed fulminant hepatitis and died. Comparisons were also made between AHB and acute infections with hepatitis A (HA) and hepatitis E (HE) viruses. During the study period, the number of patients with AHB exceeded the sum of those with acute HA and acute HE infections. There was no distinct seasonal peak for AHB infection, whereas both acute HA and acute HE infections occurred more frequently in the spring. Clinical symptoms and physical signs were similar for all three types of hepatitis, but significant differences were seen in some biochemical parameters. In conclusion, this study suggests that symptomatic AHB is not rare in China but it seldom evolves to chronic hepatitis B.

  19. Neural Responses to Partner Rejection Cues

    PubMed Central

    Zayas, Vivian; Shoda, Yuichi; Mischel, Walter; Osterhout, Lee; Takahashi, Melissa

    2009-01-01

    Little is known about neural responses in the early automatic-stage processing of rejection cues from a partner. Event-related potentials (ERPs) offer a window to study processes that may be difficult to detect via behavioral methods. We focused on the N400 ERP component, which reflects the amount of semantic processing prompted by a target. When participants were primed by attachment-related contexts (“If I need help from my partner, my partner will be …”), rejection-related words (e.g., dismissing) elicited greater N400 amplitudes than acceptance-related words (e.g., supporting). Analyses of results for nonattachment primes suggest that these findings were not simply caused by target valence; the brain responds differentially to cues of partner rejection versus acceptance in under 300 ms. Moreover, these early-stage neurophysiological responses were heightened or dampened as a function of individuals’ adult attachment; women characterized by high anxiety and low avoidance showed the greatest N400 responses to cues of partner rejection (vs. acceptance). PMID:19493321

  20. Lack of Association between Interleukin-10 Gene Polymorphisms and Graft Rejection Risk in Kidney Transplantation Recipients: A Meta-Analysis

    PubMed Central

    Xiong, Jiachuan; Wang, Yiqin; Zhang, Ying; Nie, Ling; Wang, Daihong; Huang, Yunjian; Feng, Bing; Zhang, Jingbo; Zhao, Jinghong

    2015-01-01

    Background Interleukin-10 (IL-10) is an important immunomodulatory cytokine. Several studies focused the association between IL-10 promoter gene polymorphisms and graft rejection risk in kidney transplantation recipients. However, the results of these studies remain inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations. Methods The PubMed, Embase, and Ovid Medline databases were searched. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity. Results A total of 16 studies including 595 rejection patients and 1239 stable graft patients were included in order to study the IL-10 -1082 (rs1800896 G/A), -819 (rs1800871 C/T), -592 (rs1800872 C/A) and IL-10 (-1082,-819,-592) polymorphisms. The -1082 G/A polymorphism was not associated with an increased graft rejection risk (OR = 1.03; 95%CI, 0.85–1.25, P = 0.74 for GA+AA vs. GG model). Moreover, all of the -819 C/T (OR = 1.06, 95%CI, 0.79–1.42, P = 0.70 for TA+TT vs. CC model), -592 C/A (OR = 1.10, 95% CI, 0.85–1.42, P = 0.47 for AC+AA vs. CC model) and IL-10 (-1082,-819,-592) polymorphisms (OR = 1.00, 95%CI, 0.79–1.27, P = 0.98 for I+L vs. H model) did not increase the graft rejection risk. In addition, we also performed subgroup analysis by ethnic group (mainly in Europeans or Asians) and rejection type (acute or chronic). There was also lack of evidence of a significant association between the IL-10 gene polymorphism and graft rejection risk. The present meta-analysis indicated that the IL-10 gene polymorphism was not associated with graft rejection risk in kidney transplantation recipients. Conclusion This meta-analysis found evidence that the IL-10 polymorphism does not increase the risk of graft rejection in kidney transplantation recipients. Further chronic rejection and other ethnic population studies are needed

  1. 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.

  2. Redefining late acute graft pancreatitis: clinical presentation, radiologic findings, principles of management, and prognosis.

    PubMed

    Small, Risa M; Shetzigovski, Ilanit; Blachar, Arye; Sosna, Jacob; Klausner, Joseph M; Nakache, Richard; Ben-Haim, Menahem

    2008-06-01

    To define the incidence, clinical presentation, radiologic findings and principles of diagnosis, and management of acute graft pancreatitis occurring more than 3 months after transplantation. Acute graft pancreatitis is a frequent late complication after simultaneous pancreas-kidney transplantation (SPKT) with enteric drainage that is not well understood. We performed a retrospective analysis of data from patients who underwent SPKT with enteric drainage at our institution. All recipients who experienced episodes that met the clinical criteria for late graft pancreatitis were included. We excluded events proven to be anastomotic or duodenal stump leaks. Clinical presentation, laboratory findings, radiologic imaging, course of management, and graft and patient outcome were evaluated and analyzed. Of 79 SPKTs (1995-2007), 11 (14%) recipients experienced 31 episodes of late graft pancreatitis (average number per patient, 3; range, 1-13), occurring an average of 28 months after transplantation (range, 3 months to 8 years). All patients presented with right lower quadrant abdominal peritonitis, fever, and findings compatible with pancreas graft inflammation on computed tomography or ultrasound imaging. Mild hyperamylasemia (>110 IU/L) was found in 82% of cases. Treatment was conservative, including bowel rest, antibiotics, and percutaneous sampling and drainage of abscesses as necessary. Excellent graft and patient survival were achieved. The diagnosis of late acute graft pancreatitis is clinical, with confirmatory computed tomography or ultrasound imaging. Conservative treatment yields excellent graft and patient survival.

  3. Emotion Dysregulation Mediates the Relation between Mindfulness and Rejection Sensitivity.

    PubMed

    Velotti, Patrizia; Garofalo, Carlo; Bizzi, Fabiola

    2015-09-01

    The role of rejection sensitivity (RS; the tendency to anxiously expect, readily perceive, and overreact to implied or overt interpersonal rejection) in psychopathology has mainly been studied with regard to borderline personality disorder (BPD). In the present study, we first sought to extend previous evidence of heightened RS in a clinical group with psychiatric disorders other than BPD, when compared with a community sample. Then, we tested whether emotion dysregulation and mindfulness were associated with RS in both sample, further hypothesizing that emotion dysregulation would mediate the relation between mindfulness deficits and RS. We adopted a cross-sectional design involving 191 psychiatric patients and 277 community participants (total N=468). All participants completed the Rejection Sensitivity Questionnaire, the Five Facet Mindfulness Questionnaire, and the Difficulties in Emotion Regulation Scale. Our hypotheses were supported, with psychiatric patients reporting greater levels of rejection sensitivity and emotion dysregulation, and lower level of mindfulness. Mindfulness deficits and emotion dysregulation explained a significant amount of variance in RS, in both samples. Finally, bootstrap analyses revealed that mindfulness deficits played an indirect effect on RS through the mediating role of emotion dysregulation. In particular, two different patterns emerged. Among psychiatric patients, an impairment in the ability to assume a non-judgmental stance towards own thoughts and feelings was related to RS through the mediation of limited access to emotion regulation strategies. Conversely, in the community sample, overall emotion dysregulation mediated the effect of lack of attention and awareness for present activities and experience on RS. Longitudinal studies could help in delineating etiological models of RS, and the joint role of deficits in mindfulness and emotion regulation should inform treatment programs.

  4. Clinical Significance of A Waves in Acute Inflammatory Demyelinating Polyradiculoneuropathy.

    PubMed

    Lakshminarasimhan, Sindhuja; Venkatraman, Chandramouleeswaran; Vellaichamy, Kannan; Ranganathan, Lakshminarasimhan

    2018-05-25

    A wave is a late response recognized during recording of F waves. Though they might be seen in healthy subjects, their presence assumes significance in a patient presenting with polyradiculoneuropathy. In this prospective study, 75 patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) were enrolled. They were divided into two groups based on the presence or absence of A waves. Clinical features, electrophysiological parameters and extent of clinical recovery in short-term follow-up were analyzed. A waves were present in 49 out of 75 patients (65%). Most common pattern observed was multiple A waves. Prevalence of A waves was more in lower limb nerves than upper limb nerves. Occurrence of A waves correlated with the presence of conduction block. Patients with A waves had higher Hughes grade (P = 0.003) and lower Medical Research Council sum score at 6 weeks of follow-up (P = 0.04) as compared to patients without A waves. A waves are common in acute inflammatory demyelinating polyradiculoneuropathy form of Guillain Barre syndrome and are considered as a marker of demyelination. Long-term follow-up studies are required to ascertain their significance in prognostication and assessing recovery.

  5. Clinical Features of Pregnancy-associated Retinal and Choroidal Diseases Causing Acute Visual Disturbance.

    PubMed

    Park, Young Joo; Park, Kyu Hyung; Woo, Se Joon

    2017-08-01

    To report clinical features of patients with retinal and choroidal diseases presenting with acute visual disturbance during pregnancy. In this retrospective case series, patients who developed acute visual loss during pregnancy (including puerperium) and visited a tertiary hospital from July 2007 to June 2015, were recruited by searching electronic medical records. Patients were categorized according to the cause of visual loss. Clinical features and required diagnostic modalities were analyzed in the retinal and choroidal disease group. Acute visual loss occurred in 147 patients; 49 (38.9%) were classified into the retinal and choroidal group. The diagnoses included central serous chorioretinopathy (22.4%), hypertensive retinopathy with or without pre-eclampsia (22.4%), retinal tear with or without retinal detachment (18.4%), diabetic retinopathy progression (10.2%), Vogt-Koyanagi-Harada disease (4.1%), retinal artery occlusion (4.1%), multiple evanescent white dot syndrome (4.1%), and others (14.3%). Visual symptoms first appeared at gestational age 25.9 ± 10.3 weeks. The initial best-corrected visual acuity (BCVA) was 0.27 ± 0.39 logarithm of the minimum angle of resolution (logMAR); the final BCVA after delivery improved to 0.13 ± 0.35 logMAR. Serious visual deterioration (BCVA worth than 20 / 200) developed in two patients. Differential diagnoses were established with characteristic fundus and spectral-domain optical coherence tomography findings in all cases. In pregnant women with acute visual loss, retinal and choroidal diseases are common and could be vision threatening. Physicians should be aware of pregnancy-associated retinal and choroidal diseases and their clinical features. The differential diagnosis can be established with non-invasive techniques. © 2017 The Korean Ophthalmological Society

  6. Clinical Risk Factors for In-Hospital Adverse Cardiovascular Events After Acute Drug Overdose

    PubMed Central

    Manini, Alex F.; Hoffman, Robert S.; Stimmel, Barry; Vlahov, David

    2015-01-01

    Objectives It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. Methods This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. Results There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] 27.6), bicarbonate < 20 mEql/L (5.4% prevalence, OR 4.4), and prior cardiac disease (7.1% prevalence, OR 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value; while presence of two or more risk factors had 90.9% positive predictive value. Conclusions The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings. PMID:25903997

  7. Soluble donor HLA class I and beta 2m-free heavy chain in serum of lung transplant recipients: steady-state levels and increases in patients with recurrent CMV infection, acute rejection episodes, and poor outcome.

    PubMed

    DeVito-Haynes, L D; Jankowska-Gan, E; Meyer, K C; Cornwell, R D; Zeevi, A; Griffith, B; Dauber, J; Iacono, A; Burlingham, W J; Love, R B

    2000-12-01

    We determined the concentration of donor sHLA/beta(2)m and total beta(2)m-free heavy chain (HC) in the serum of lung transplant recipients with ELISA assays. While we were unable to detect specific donor beta(2)m-free HCs due to a lack of available antibodies, we could determine if events that led to an increase in the release of beta(2)m-free HC also led to an increase in the release of donor sHLA/beta(2)m, particularly the 36 kDa, proteolytically cleaved form. We found that lung transplants constituitively release donor sHLA/beta(2)m at ng/ml levels. The levels (both of donor sHLA/beta(2)m and total beta(2)m-free HC) were significantly increased in CMV-sero-negative recipients (but not in CMV-sero-positive recipients) at the onset of post-transplant CMV disease. Acute rejection episodes were also associated with an increased release of donor sHLA/beta(2)m, but not of beta(2)m-free HC. However, in patients with particularly poor outcome (i.e., graft loss within 1 year) there was a significant release of beta(2)m-free HC. Analysis of one such patient showed a predominance of 36 kDa forms of donor-sHLA/beta(2)m. Our data are consistent with the hypothesis that the metalloproteinase that cleaves beta(2)m-free HC is active during uncontrolled CMV infection and acute rejection. However, recall responses to CMV and controlled immune responses to donor may result in little or no activation of sHLA class I release.

  8. Clinical Variables Associated with Hydration Status in Acute Ischemic Stroke Patients with Dysphagia.

    PubMed

    Crary, Michael A; Carnaby, Giselle D; Shabbir, Yasmeen; Miller, Leslie; Silliman, Scott

    2016-02-01

    Acute stroke patients with dysphagia are at increased risk for poor hydration. Dysphagia management practices may directly impact hydration status. This study examined clinical factors that might impact hydration status in acute ischemic stroke patients with dysphagia. A retrospective chart review was completed on 67 ischemic stroke patients who participated in a prior study of nutrition and hydration status during acute care. Prior results indicated that patients with dysphagia demonstrated elevated BUN/Cr compared to non-dysphagia cases during acute care and that BUN/Cr increased selectively in dysphagic patients. This chart review evaluated clinical variables potentially impacting hydration status: diuretics, parenteral fluids, tube feeding, oral diet, and nonoral (NPO) status. Exposure to any variable and number of days of exposure to each variable were examined. Dysphagia cases demonstrated significantly more NPO days, tube fed days, and parenteral fluid days, but not oral fed days, or days on diuretics. BUN/Cr values at discharge were not associated with NPO days, parenteral fluid days, oral fed days, or days on diuretics. Patients on modified solid diets had significantly higher mean BUN/Cr values at discharge (27.12 vs. 17.23) as did tube fed patients (28.94 vs. 18.66). No difference was noted between these subgroups at baseline (regular diet vs. modified solids diets). Any modification of solid diets (31.11 vs. 17.23) or thickened liquids (28.50 vs. 17.81) resulted in significantly elevated BUN/Cr values at discharge. Liquid or diet modifications prescribed for acute stroke patients with dysphagia may impair hydration status in these patients.

  9. Clinical Presentation of Acute Gastroenteritis in Children With Functional Abdominal Pain Disorders.

    PubMed

    Saps, Miguel; Mintjens, Stijn; Pusatcioglu, Cenk K; Cohen, Daniel M; Sternberg, Petra

    2017-08-01

    Visceral hypersensitivity and abnormal coping are common in children with functional abdominal pain disorders (FAPDs). Thus, it would be expected that children with visceral hypersensitivity would report more pain if their gut is acutely inflamed. The aim of the study was to compare clinical symptoms and somatization of children with and without FAPDs at time of an episode of acute gastroenteritis. Seventy children with acute gastroenteritis and their parents completed the Rome III Diagnostic Questionnaire for Pediatric Functional GI Disorders and the Children's Somatization Inventory. Twenty-one percent of children were diagnosed with an FAPD. Children with FAPDs showed significantly more nongastrointestinal somatic symptoms than children without FAPDs. There were no significant differences in abdominal pain, nausea, vomiting, or school absenteeism between both groups at time of consultation.

  10. Clinical and Genetic Risk Factors for Acute Pancreatitis in Patients With Acute Lymphoblastic Leukemia

    PubMed Central

    Liu, Chengcheng; Yang, Wenjian; Devidas, Meenakshi; Cheng, Cheng; Pei, Deqing; Smith, Colton; Carroll, William L.; Raetz, Elizabeth A.; Bowman, W. Paul; Larsen, Eric C.; Maloney, Kelly W.; Martin, Paul L.; Mattano, Leonard A.; Winick, Naomi J.; Mardis, Elaine R.; Fulton, Robert S.; Bhojwani, Deepa; Howard, Scott C.; Jeha, Sima; Pui, Ching-Hon; Hunger, Stephen P.; Evans, William E.; Loh, Mignon L.

    2016-01-01

    Purpose Acute pancreatitis is one of the common causes of asparaginase intolerance. The mechanism is unknown, and genetic predisposition to asparaginase-induced pancreatitis has not been previously identified. Methods To determine clinical risk factors for asparaginase-induced pancreatitis, we studied a cohort of 5,185 children and young adults with acute lymphoblastic leukemia, including 117 (2.3%) who were diagnosed with at least one episode of acute pancreatitis during therapy. A genome-wide association study was performed in the cohort and in an independent case-control group of 213 patients to identify genetic risk factors. Results Risk factors associated with pancreatitis included genetically defined Native American ancestry (P < .001), older age (P < .001), and higher cumulative dose of asparaginase (P < .001). No common variants reached genome-wide significance in the genome-wide association study, but a rare nonsense variant rs199695765 in CPA2, encoding carboxypeptidase A2, was highly associated with pancreatitis (hazard ratio, 587; 95% CI, 66.8 to 5166; P = 9.0 × 10−9). A gene-level analysis showed an excess of additional CPA2 variants in patients who did versus those who did not develop pancreatitis (P = .001). Sixteen CPA2 single-nucleotide polymorphisms were associated (P < .05) with pancreatitis, and 13 of 24 patients who carried at least one of these variants developed pancreatitis. Biologic functions that were overrepresented by common variants modestly associated with pancreatitis included purine metabolism and cytoskeleton regulation. Conclusion Older age, higher exposure to asparaginase, and higher Native American ancestry were independent risk factors for pancreatitis in patients with acute lymphoblastic leukemia. Those who inherit a nonsense rare variant in the CPA2 gene had a markedly increased risk of asparaginase-induced pancreatitis. PMID:27114598

  11. 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. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  12. Sub-clinical Alcohol Consumption and Gambling Disorder.

    PubMed

    Harries, Michael D; Redden, Sarah A; Leppink, Eric W; Chamberlain, Samuel R; Grant, Jon E

    2017-06-01

    While it is well established that gambling disorder is associated with alcohol use disorder, less is known regarding whether sub-clinical alcohol consumption increases gambling behavior. This study examined the effects of varying levels of alcohol consumption on clinical and cognitive measures. The sample consisted of 572 non-treatment seeking gamblers age 18-29 who were divided into three groups: non-current drinkers, current drinkers who did not qualify for an alcohol use disorder, and those with an alcohol use disorder (AUD). All subjects were assessed on gambling pathology, severity and impulsivity using the Structured Clinical Interview for Gambling Disorder, Yale Brown Obsessive Compulsive Scale for Pathologic Gambling and the Barratt Impulsive Scale-11 and select cognitive tests. In all of the clinical measures, controlling for age, gender and education, the AUD group was significantly more likely than the non-current and current drinkers to be a pathologic gambler and to be impulsive, compulsive and depressed. On cognitive tasks, controlling for age, gender and education, the AUD group had significantly worse strategy use on a spatial working memory task than both other groups. This study suggests that the relationship between alcohol and gambling may only exist when pathology in both alcohol consumption and gambling behavior is present. Examining this relationship with alcohol consumption as a continuous variable would provide additional insight into the potential effects alcohol consumption has on gambling behavior.

  13. Clinical characteristics of acute hepatitis A outbreak in Taiwan, 2015-2016: observations from a tertiary medical center.

    PubMed

    Chen, Nan-Yu; Liu, Zhuo-Hao; Shie, Shian-Sen; Chen, Tsung-Hsing; Wu, Ting-Shu

    2017-06-20

    Acute hepatitis A is a fecal-oral transmitted disease related to inadequate sanitary conditions. In addition to its traditional classification, several outbreaks in the men who have sex with men (MSM) population have resulted in acute hepatitis A being recognized as a sexually transmitted disease. However, few studies have clarified the clinical manifestations in these outbreaks involving the MSM population. Beginning in June 2015, there was an outbreak of acute hepatitis A involving the MSM population in Northern Taiwan. We conducted a 15-year retrospective study by recruiting 207 patients with the diagnosis of acute hepatitis A that included the pre-outbreak (January 2001 to May 2015) and outbreak (June 2015 to August 2016) periods in a tertiary medical center in Northern Taiwan. Using risk factors, comorbidities, presenting symptoms, laboratory test results and imaging data, we aimed to evaluate the clinical significance of acute hepatitis A in the MSM population, where human immunodeficiency virus (HIV) coinfection is common. There was a higher prevalence of reported MSM (p < 0.001), HIV (p < 0.001) and recent syphilis (p < 0.05) coinfection with acute hepatitis A during the outbreak period. The outbreak population had more prominent systemic symptoms, was more icteric with a higher total bilirubin level (p < 0.05) and had a 7-times higher tendency (p < 0.05) to have a hepatitis A relapse. The clinical course of acute hepatitis A during an outbreak involving the MSM and HIV-positive population is more symptomatic and protracted than in the general population.

  14. The Parental "Acceptance-Rejection Syndrome": Universal Correlates of Perceived Rejection

    ERIC Educational Resources Information Center

    Rohner, Ronald P.

    2004-01-01

    This article reviews theory, methods, and evidence supporting the concept of a relational diagnosis here called the parental acceptance-rejection syndrome. This syndrome is composed of 2 complementary sets of factors. First, 4 classes of behaviors appear universally to convey the symbolic message that "my parent (or other attachment…

  15. Clinical use of MRI for the evaluation of acute appendicitis during pregnancy.

    PubMed

    Patel, Darshan; Fingard, Jordan; Winters, Sean; Low, Gavin

    2017-07-01

    The purpose of this study was to determine the diagnostic accuracy of MRI for detecting acute appendicitis in pregnancy in a multi-institution study involving general body MR readers with no specific expertise in MR imaging of the pregnant patient. Retrospective review of MRI examinations on PACS in 42 pregnant patients was evaluated for acute right lower quadrant pain. Three fellowship-trained general body radiologists analyzed the MRI examinations in consensus and attempted to localize the appendix, assess for features of appendicitis, and exclude alternative etiologies for the right lower quadrant pain. Of the 42 MRI examinations, the readers noted 6 cases of acute appendicitis, 16 cases of a normal appendix, and 20 cases involving non-visualization of the appendix but where there were no secondary features of acute appendicitis. Based on the surgical data and clinical follow-up, there were 3 true-positive cases, 3 false-positive cases, 34 true-negative cases, and 2 false-negative cases of acute appendicitis on MRI. This yielded an accuracy of 88.1%, sensitivity of 60%, specificity of 91.9%, positive predictive value of 50%, and negative predictive value of 94.4% for the detection of acute appendicitis in the pregnant patient on MRI. Alternative etiologies for the right lower quadrant pain on MRI included torsion of an ovarian dermoid in 1 case and pyelonephritis in 1 case. MRI is an excellent modality for excluding acute appendicitis in pregnant patients presenting with right lower quadrant pain.

  16. Diagnosis of Acute Cellular Rejection Using Probe-Based Confocal Laser Endomicroscopy in Lung Transplant Recipients: a Prospective, Multicenter Trial.

    PubMed

    Keller, Cesar A; Khoor, Andras; Arenberg, Douglas A; Smith, Michael A; Islam, Shaheen U

    2018-05-29

    Acute cellular rejection (ACR) in lung transplant recipients requires demonstration of perivascular lymphocytic infiltration in alveolar tissue samples from transbronchial biopsies (TBBs). Probe-based confocal laser endomicroscopy (pCLE) allows in vivo observation of alveolar, vascular, and cellular microstructures in the lung with potential to identify ACR. The objective of our prospective, blinded, multicenter observational study was to identify pCLE findings in patients with ACR diagnosed histopathologically by TBB. Lung transplant recipients undergoing diagnostic bronchoscopies within 1 year posttransplant for suspected ACR had pCLE video imaging obtained immediately prior to tissue sampling via TBB. Findings of 2 pCLE criteria, abundant alveolar cellularity and perivascular cellularity (PVC), were assessed by 4 investigators familiar with pCLE and compared to histopathologic criteria of ACR to derive sensitivity, specificity, area under the receiver operating characteristic curve, and accuracy. Interobserver agreement was assessed by calculating intraclass coefficient and Fleiss κ. Findings were analyzed before and after a consensus meeting of investigators on interpreting images. Thirty pCLE procedures were performed on 24 patients, 8 showing ACR in TBB. Diagnostic performance and interobserver agreement using pCLE to identify PVC were significantly higher than those of abundant alveolar cellularity (P<.01). The number of blood vessels identified with PVC on pCLE was significantly correlated with histopathologic activity grading of ACR (P<.01). PVC agreement among investigators significantly improved after consensus meeting (P<.01) CONCLUSIONS: When found on pCLE, PVC is a feasible and reproducible criterion for assessment of ACR in vivo, but there is a learning curve for image interpretation.

  17. Clinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure.

    PubMed

    Matsue, Yuya; Ter Maaten, Jozine M; Struck, Joachim; Metra, Marco; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; van Veldhuisen, Dirk J; van der Meer, Peter; Damman, Kevin; Voors, Adriaan A

    2017-03-01

    Proenkephalin (pro-ENK) has emerged as a novel biomarker associated with both renal function and cardiac function. However, its clinical and prognostic value have not been well evaluated in symptomatic patients with heart failure. The association between pro-ENK and markers of renal function was evaluated in 95 patients with chronic heart failure who underwent renal hemodynamic measurements, including renal blood flow (RBF) and glomerular filtration rate (GFR) with the use of 131 I-Hippuran and 125 I-iothalamate clearances, respectively. The association between pro-ENK and clinical outcome in acute heart failure was assessed in another 1589 patients. Pro-ENK was strongly correlated with both RBF (P < .001) and GFR (P < .001), but not with renal tubular markers. In the acute heart failure cohort, pro-ENK was a predictor of death through 180 days, heart failure rehospitalization through 60 days, and death or cardiovascular or renal rehospitalization through day 60 in univariable analyses, but its predictive value was lost in a multivariable model when other renal markers were entered in the model. In patients with chronic and acute heart failure, pro-ENK is strongly associated with glomerular function, but not with tubular damage. Pro-ENK provides limited prognostic information in patients with acute heart failure on top of established renal markers. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Rejection of Bromide and Bromate Ions by a Ceramic Membrane.

    PubMed

    Moslemi, Mohammadreza; Davies, Simon H; Masten, Susan J

    2012-12-01

    Effects of pH and the addition of calcium chloride (CaCl(2)) on bromate (BrO(3) (-)) and bromide (Br(-)) rejection by a ceramic membrane were investigated. Rejection of both ions increased with pH. At pH 8, the rejection of BrO(3) (-) and Br(-) was 68% and 63%, respectively. Donnan exclusion appears to play an important role in determining rejection of BrO(3) (-) and Br(-). In the presence of CaCl(2), rejection of BrO(3) (-) and Br(-) ions was greatly reduced, confirming the importance of electrostatic interactions in determining rejection of BrO(3) (-) and Br(-). The effect of Ca(2+) is so pronounced that in most natural waters, rejection of both BrO(3) (-) and Br(-) by the membrane would be extremely small.

  19. Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.

    PubMed

    Garg, Amit X; Kurz, Andrea; Sessler, Daniel I; Cuerden, Meaghan; Robinson, Andrea; Mrkobrada, Marko; Parikh, Chirag R; Mizera, Richard; Jones, Philip M; Tiboni, Maria; Font, Adrià; Cegarra, Virginia; Gomez, Maria Fernanda Rojas; Meyhoff, Christian S; VanHelder, Tomas; Chan, Matthew T V; Torres, David; Parlow, Joel; Clanchet, Miriam de Nadal; Amir, Mohammed; Bidgoli, Seyed Javad; Pasin, Laura; Martinsen, Kristian; Malaga, German; Myles, Paul; Acedillo, Rey; Roshanov, Pavel S; Walsh, Michael; Dresser, George; Kumar, Priya; Fleischmann, Edith; Villar, Juan Carlos; Painter, Thomas; Biccard, Bruce; Bergese, Sergio; Srinathan, Sadeesh; Cata, Juan P; Chan, Vincent; Mehra, Bhupendra; Wijeysundera, Duminda N; Leslie, Kate; Forget, Patrice; Whitlock, Richard; Yusuf, Salim; Devereaux, P J

    2014-12-03

    Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm. To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery. Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery. Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine

  20. Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials.

    PubMed

    Serebruany, Victor L; Glassman, Alexander H; Malinin, Alex I; Sane, David C; Finkel, Mitchell S; Krishnan, Ranga R; Atar, Dan; Lekht, Vladimir; O'Connor, Christopher M

    2003-09-01

    Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective