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Sample records for acute rejection episode

  1. Imaging-based diagnosis of acute renal allograft rejection

    PubMed Central

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

    2016-01-01

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

  2. Renal graft irradiation in acute rejection

    SciTech Connect

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

    1983-03-01

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

  3. The biology of acute transplant rejection.

    PubMed Central

    Tilney, N L; Kupiec-Weglinski, J W

    1991-01-01

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

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

    PubMed Central

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

    2014-01-01

    Molecular imaging techniques such as single photon emission computed tomography (SPECT) or positron emission tomography are promising tools for noninvasive diagnosis of acute allograft rejection (AR). Given the importance of renal transplantation and the limitation of available donors, detailed analysis of factors that affect transplant survival is important. Episodes of acute allograft rejection are a negative prognostic factor for long-term graft survival. Invasive core needle biopsies are still the “goldstandard” in rejection diagnostics. Nevertheless, they are cumbersome to the patient and carry the risk of significant graft injury. Notably, they cannot be performed on patients taking anticoagulant drugs. Therefore, a noninvasive tool assessing the whole organ for specific and fast detection of acute allograft rejection is desirable. We herein review SPECT- and PET-based approaches for noninvasive molecular imaging-based diagnostics of acute transplant rejection. PMID:24804257

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

    PubMed Central

    NACIF, Lucas Souto; PINHEIRO, Rafael Soares; PÉCORA, Rafael Antônio de Arruda; DUCATTI, Liliana; ROCHA-SANTOS, Vinicius; ANDRAUS, Wellington; D'ALBUQUERQUE, Luiz Carneiro

    2015-01-01

    Introduction: Late acute rejection leads to worse patient and graft survival after liver transplantation. Aim: To analyze the reported results published in recent years by leading transplant centers in evaluating late acute rejection and update the clinical manifestations, diagnosis and treatment of liver transplantation. Method: Systematic literature review through Medline-PubMed database with headings related to late acute rejection in articles published until November 2013 was done. Were analyzed demographics, immunosuppression, rejection, infection and graft and patient survival rates. Results: Late acute rejection in liver transplantation showed poor results mainly regarding patient and graft survival. Almost all of these cohort studies were retrospective and descriptive. The incidence of late acute rejection varied from 7-40% in these studies. Late acute rejection was one cause for graft loss and resulted in different outcomes with worse patient and graft survival after liver transplant. Late acute rejection has been variably defined and may be a cause of chronic rejection with worse prognosis. Late acute rejection occurs during a period in which the goal is to maintain lower immunosuppression after liver transplantation. Conclusion: The current articles show the importance of late acute rejection. The real benefit is based on early diagnosis and adequate treatment at the onset until late follow up after liver transplantation. PMID:26537150

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

    PubMed Central

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

    2011-01-01

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

  7. Anabolic steroids and acute schizophrenic episode.

    PubMed

    Annitto, W J; Layman, W A

    1980-04-01

    The use of anabolic steroids by athletes to increase physical performance has vastly increased over the last 10 years. A case is described which temporally relates the use of these organic compounds with the development of an acute schizophreniform illness. The dearth of literature on this particular "side-effect" is noted, as are the diagnostic implications vis-a-vis anabolic steroids and the anamnestic interview in an athlete who presents with an acute schizophrenic mental status examination. Recommendation is made to consider this "side-effect" in differential diagnosis of schizophrenic episode. PMID:7364737

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1996-05-27

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

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

    PubMed Central

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

    1991-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  13. Early diagnosis of acute postoperative renal transplant rejection

    SciTech Connect

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

    1985-05-01

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

  14. Recollection rejection of new items in individuals with first-episode psychosis.

    PubMed

    Guimond, Synthia; Lepage, Martin; Benoit, Audrey; Charbonneau, Geneviève; Hawco, Colin; Malla, Ashok K; Joober, Ridha; Brodeur, Mathieu B

    2016-01-01

    Many objects seen for the first time look familiar because they resemble known objects. To overcome this feeling of familiarity and detect novelty, memories of known objects must be recollected and compared to new objects. This experiment examines whether recollection performed when perceiving new items (i.e., recollection rejection) is abnormal in people who experienced a first episode of psychosis (FEP). Recollection of old items is impaired in this clinical population but it has not yet been demonstrated that this impairment influences the processing of new items. Eighteen FEP participants and 19 healthy controls completed an episodic memory task consisting of a study phase and a recognition phase. All the new objects looked familiar because they resembled the studied objects. Brain activity underlying false recognition and correct rejection of new objects was measured with functional resonance magnetic imaging and compared across groups. Behavioral responses to new items were not significantly different between the 2 groups. However, the between-groups analysis revealed significant differences in brain activity in the left middle frontal gyrus, the left inferior parietal lobule, the right superior parietal lobule, and the right temporal fusiform gyrus during the correct rejection of new items. This activity seems related to recollection rejection and suggests that FEP patients do not normally recollect information of past events when they process new items. PMID:26726818

  15. Respiratory symptoms and acute painful episodes in sickle cell disease.

    PubMed

    Jacob, Eufemia; Sockrider, Marianna M; Dinu, Marlen; Acosta, Monica; Mueller, Brigitta U

    2010-01-01

    The authors examined the prevalence of respiratory symptoms and determined whether respiratory symptoms were associated with prevalence of chest pain and number of acute painful episodes in children and adolescents with sickle cell disease. Participants (N = 93; 44 females, 49 males; mean age 9.8 +/- 4.3 years) reported coughing in the morning (21.5%), at night (31.2%), and during exercise (30.1%). Wheezing occurred both when they had a cold or infection (29.0%) and when they did not have (23.7%) a cold or infection. Sleep was disturbed by wheezing in 20.4%. Among the 76 patients who were school-age (>5 years), 19.7% of patients missed more than 4 days of school because of respiratory symptoms. The majority of patients reported having acute painful episodes (82.8%), and most (66.7%) reported having chest pain during acute painful episodes in the previous 12 months. Participants with acute pain episodes greater than 3 during the previous 12 months had significantly higher reports of breathing difficulties (P = .01) and chest pain (P = .002). The high number of respiratory symptoms (cough and wheeze) among patients with sickle cell disease may trigger acute painful episodes. Early screening and recognition, ongoing monitoring, and proactive management of respiratory symptoms may minimize the number of acute painful episodes. PMID:20038672

  16. Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection.

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. 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

  19. Pycnogenol treatment of acute hemorrhoidal episodes.

    PubMed

    Belcaro, Gianni; Cesarone, Maria Rosaria; Errichi, Bruno; Di Renzo, Andrea; Grossi, Maria Giovanna; Ricci, Andrea; Dugall, Mark; Cornelli, Umberto; Cacchio, Marisa; Rohdewald, Peter

    2010-03-01

    We investigated the efficacy of orally and topically applied Pycnogenol for the management of acute hemorrhoidal attacks in a controlled, randomized study with 84 subjects. Within less than 48 h of onset of an acute attack, patients were enrolled and signs and symptoms were scored. This evaluation was repeated after seven days' treatment and again seven days following treatment cessation. The decrease in scores was significantly more pronounced in the Pycnogenol-treated groups than in the control group given placebo (p < 0.05), showing the efficacy of Pycnogenol for relieving signs and symptoms of acute external hemorrhoids. In a group of patients given topical (0.5%) Pycnogenol in addition to oral Pycnogenol the improvement in symptoms set in significantly faster and was more pronounced. The most prominent symptom, hemorrhoidal bleeding, was completely absent in all patients treated with Pycnogenol for seven days and also at the 14 days follow-up. In contrast, bleedings were still observed in the control group during the two weeks follow-up. This study indicates that Pycnogenol, both in oral and in topical form, is effective for controlling this common, disabling health problem. The application of Pycnogenol eases the management of acute hemorrhoidal attacks and help avoid bleedings. PMID:20041428

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

    PubMed Central

    2012-01-01

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

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

    PubMed

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

    2015-08-01

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

  2. Meteorological parameters and severity of acute pulmonary embolism episodes.

    PubMed

    Staśkiewicz, Grzegorz; Czekajska-Chehab, Elżbieta; Przegaliński, Jerzy; Maciejewski, Marcin; Pachowicz, Marcin; Drop, Andrzej

    2011-01-01

    Frequency of acute pulmonary embolism episodes has been previously shown to correlate significantly with meteorological factors in the period preceding their occurrence. The purpose of the study was to analyze the relation of meteorological factors and the severity of acute pulmonary embolism, expressed by the CT-based pulmonary obstruction score. A retrospective analysis of medical data of 182 consecutive patients with acute pulmonary embolism diagnosed with CT pulmonary angiography was performed. Severity of pulmonary obstruction was assessed by analysis of CT pulmonary angiography examinations, and defined with pulmonary obstruction score by Qanadli et al. The study group was divided into low (L group, 95 patients) and high PE severity (H group, 87 patients), with a cutoff value of 50% of maximum pulmonary obstruction score. Meteorological data collected for the relevant time period were: air temperature, humidity, atmospheric pressure, visibility, wind speed and precipitation. No significant differences in seasonal distribution of pulmonary embolism episodes were observed. Episodes of more severe pulmonary embolism were preceded by periods of lower atmospheric pressure (1,016.35 hPA for group H, vs. 1,016.35 hPa for group L, p = 0.022). No significant relations between other meteorological factors and severity of PE were observed. The reported finding shows the need of further research on the nature of meteorological factors influence on the course of pulmonary embolism, which should be analyzed not ony regarding the frequency, but also severity of PE episodes. PMID:21736277

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

    PubMed Central

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

    1997-01-01

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

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

  4. Macrolides for Acute Wheezing Episodes in Preschool Children

    PubMed Central

    Blake, Kathryn

    2016-01-01

    The National Asthma Education and Prevention Program's Expert Panel Report 3, Guidelines for the Diagnosis and Management of Asthma does not recommend antibiotics for the management of acute episodes of asthma exacerbation. Macrolides seem to have some potential effect beyond or in addition to their antibacterial effect. It has been reported that macrolides may potentially benefit patients with chronic inflammatory airway diseases due to their antibacterial, antiviral, and/or anti-inflammatory effects. This review presents recent data on use of azithromycin in prevention and management of acute exacerbation of respiratory symptoms in infants and young children. PMID:27458539

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    SciTech Connect

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

    2010-01-04

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

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

    PubMed

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

    2014-05-01

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

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

    PubMed Central

    Zakrzewicz, Anna; Atanasova, Srebrena; Padberg, Winfried

    2015-01-01

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

  10. The effects of an acute psychosocial stressor on episodic memory

    PubMed Central

    Stawski, Robert S.; Sliwinski, Martin J.; Smyth, Joshua M.

    2009-01-01

    Although stressors are believed to impair memory, experimental studies with humans have provided inconsistent support for this conclusion. The current study was designed to examine the effect of an acute psychosocial stressor, and subsequent reactivity, on episodic memory. One hundred participants completed a list-recall task before and after random assignment into a stressor or nonstressor condition. Participants assigned to the stressor condition exhibited both impaired delayed and immediate recall, and also exhibited increasesin the commission of intrusions and perseverations. The experience of off-task thoughts and intentional suppression of such thoughts, were associated with greater impairment of immediate recall. Changes in state anxiety, negative mood, and heart rate were unrelated to changes in memory. These data indicate that exposure to a stressor impaired the recall of previously learned information, and compromised the recall of newly acquired information. Furthermore, cognitive interference is an important factor regarding stress-related impairments of episodic memory. memory. PMID:19727439

  11. Cognitive deficits in bipolar disorder: from acute episode to remission.

    PubMed

    Volkert, J; Schiele, M A; Kazmaier, Julia; Glaser, Friederike; Zierhut, K C; Kopf, J; Kittel-Schneider, S; Reif, A

    2016-04-01

    Considerable evidence demonstrates that neuropsychological deficits are prevalent in bipolar disorder during both acute episodes and euthymia. However, it is less clear whether these cognitive disturbances are state- or trait-related. We here present the first longitudinal study employing a within-subject pre- and post-testing examining acutely admitted bipolar patients (BP) in depression or mania and during euthymia, aiming to identify cognitive performance from acute illness to remission. Cognitive performance was measured during acute episodes and repeated after at least 3 months of remission. To do so, 55 BP (35 depressed, 20 hypo-/manic) and 55 healthy controls (HC) were tested with a neuropsychological test battery (attention, working memory, verbal memory, executive functioning). The results showed global impairments in acutely ill BP compared to HC: depressed patients showed a characteristic psychomotor slowing, while manic patients had severe deficits in executive functioning. Twenty-nine remitted BP could be measured in the follow-up (dropout rate 48 %), whose cognitive functions partially recovered, whereas working memory and verbal memory were still impaired. However, we found that subthreshold depressive symptoms and persisting sleep disturbances in euthymic BP were associated with reduced speed, deficits in attention and verbal memory, while working memory was correlated with psychotic symptoms (lifetime). This result indicates working memory as trait related for a subgroup of BP with psychotic symptoms. In contrast, attention and verbal memory are negatively influenced by state factors like residual symptoms, which should be more considered as possible confounders in the search of cognitive endophenotypes in remitted BP. PMID:26611783

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

    PubMed

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

    2011-10-01

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

  13. The acute and preventative treatment of episodic migraine

    PubMed Central

    Miller, Sarah

    2012-01-01

    Episodic migraine is a common debilitating condition with significant worldwide impact. An effective management plan must include acute treatment to relieve the pain and potential disability associated with the attacks and may also include preventative treatments with an aim of decreasing attack frequency and severity in the longer term. Acute treatments must be limited to a maximum of 2-3 days a week to prevent medication overuse headache and focus on simple analgesia, non-steroidal anti-inflammatory drugs and triptans. Preventative treatments are numerous and should be considered when migraine attacks are frequent and or disabling, acute medication is failing, in special circumstances such as hemiplegic migraines or if the patient requests them. All preventative medications must be given at therapeutic doses for at least 6-8 weeks before an adequate trial can be judged ineffective. The most important factor in choosing drugs is the patient and the clinical features of their attack and treatment should be tailored to these. Relative co-morbidities will influence drug choice, as will the side effect profile and the efficacy of the drug. First line preventative drugs include ß-blockers, amitriptyline and anti-epileptic drugs such as topiramate and valproate. Drugs with lower efficacy or poorer side effect profiles include selective serotonin reuptake inhibitors (SSRIs), calcium channel antagonists, gabapentin and herbal medicines. PMID:23024562

  14. 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.

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

    PubMed

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

    2008-04-01

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

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

    SciTech Connect

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

    1988-11-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Pieper, Galen M.; Roza, Allan M.

    2008-01-01

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

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

    PubMed

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

    2010-03-01

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

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

    PubMed

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

    2008-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2001-06-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    1988-01-01

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

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

    PubMed

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

    2012-03-01

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

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

    PubMed

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

    2014-01-01

    Acute skin rejection in vascularized composite allotransplantation (VCA) is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection. PMID:24926998

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    1995-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. 19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells.

    PubMed

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

    2011-04-01

    Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure.We have previously shown that cellular magnetic resonance imaging (MRI) of iron-oxide labeled immune-cell infiltration can provide a noninvasive measure of rejection status by detecting areas of hypointensity on T 2*-weighted images. In this study, we tested the feasibility of using a fluorine-based cellular tracer agent to detect macrophage accumulation in rodent models of acute allograft rejection by fluorine-19 ((19) F) MRI and magnetic resonance spectroscopy. This study used two rat models of acute rejection, including abdominal heterotopic cardiac transplant and orthotopic kidney transplant models. Following in vivo labeling of monocytes and macrophages with a commercially available agent containing perfluoro-15-crown-5-ether, we observed (19) F-signal intensity in the organs experiencing rejection by (19) F MRI, and conventional (1) H MRI was used for anatomical context. Immunofluorescence and histology confirmed macrophage labeling. These results are consistent with our previous studies and show the complementary nature of the two cellular imaging techniques. With no background signal, (19) F MRI/magnetic resonance spectroscopy can provide unambiguous detection of fluorine labeled cells, and may be a useful technique for detecting and quantifying rejection grade in patients. PMID:21305593

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. Acute Hepatic Phenotype of Wilson Disease: Clinical Features of Acute Episodes and Chronic Lesions Remaining in Survivors

    PubMed Central

    Hayashi, Hisao; Tatsumi, Yasuaki; Yahata, Shinsuke; Hayashi, Hiroki; Momose, Kenji; Isaji, Ryohei; Sasaki, Youji; Hayashi, Kazuhiko; Wakusawa, Shinya; Goto, Hidemi

    2015-01-01

    Background and Aims: Wilson disease (WD) is an inherited disorder of copper metabolism, and an international group for the study of WD (IGSW) has proposed three phenotypes for its initial presentation: acute hepatic, chronic hepatic, and neurologic phenotypes. Characterization of the acute hepatic phenotype may improve our understanding of the disease. Methods: Clinical features of 10 WD patients with the acute hepatic phenotype and characteristics of chronic lesions remaining in survivors were assessed by the European Association for the Study of the Liver (EASL) guidelines. Results: All six patients younger than 30 years had survived an acute episode of hemolytic anemia with residual liver disease of cirrhosis or chronic hepatitis. The acute episode was self-limiting in two of the four patients over the age of 30 years and progressed to acute liver failure in the other two patients. One of the two survivors had residual liver disease of chronic hepatitis, while the other had chronic hepatitis and neurologic disease. Neurologic disease remained in a patient who successfully received a liver transplantation. During acute episodes, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) changed rapidly along with anemia. Liver-specific ALT levels were age-dependently correlated with hemoglobin (Hb) concentrations. Enzyme reduction was milder for AST than ALT, which resulted in a high AST/ALT ratio in the anemic stage. The anemic stage in two patients transformed to acute liver failure. Conclusions: All survivors of an acute episode of the acute hepatic phenotype had residual liver disease or both liver and neurologic diseases. The rapid changes in liver enzymes during the acute episode and the liver and neurologic diseases remaining in survivors may provide a better understanding of WD. PMID:26807378

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. Psychosocial Acute Treatment in Early-Episode Schizophrenia Disorders

    ERIC Educational Resources Information Center

    Bola, John R.

    2006-01-01

    Objective: This article reviews evidence on the treatment of early episode schizophrenia spectrum disorders that contradicts, in some cases, the American Psychiatric Association's generic recommendation of antipsychotic medication treatment for at least a year. Method: Evidence on lack of diagnostic validity, absence of demonstrated long-term…

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

    PubMed

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

    2009-01-01

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

  2. Creating learning momentum through overt teaching interactions during real acute care episodes.

    PubMed

    Piquette, Dominique; Moulton, Carol-Anne; LeBlanc, Vicki R

    2015-10-01

    Clinical supervisors fulfill a dual responsibility towards patient care and learning during clinical activities. Assuming such roles in today's clinical environments may be challenging. Acute care environments present unique learning opportunities for medical trainees, as well as specific challenges. The goal of this paper was to better understand the specific contexts in which overt teaching interactions occurred in acute care environments. We conducted a naturalistic observational study based on constructivist grounded theory methodology. Using participant observation, we collected data on the teaching interactions occurring between clinical supervisors and medical trainees during 74 acute care episodes in the critical care unit of two academic centers, in Toronto, Canada. Three themes contributed to a better understanding of the conditions in which overt teaching interactions among trainees and clinical supervisors occurred during acute care episodes: seizing emergent learning opportunities, coming up against challenging conditions, and creating learning momentum. Our findings illustrate how overt learning opportunities emerged from certain clinical situations and how clinical supervisors and trainees could purposefully modify unfavorable learning conditions. None of the acute care episodes encountered in the critical care environment represented ideal conditions for learning. Yet, clinical supervisors and trainees succeeded in engaging in overt teaching interactions during many episodes. The educational value of these overt teaching interactions should be further explored, as well as the impact of interventions aimed at increasing their use in acute care environments. PMID:25476262

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Wang, Jun; Al-Lamki, Rafia S.

    2013-01-01

    Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein and one of the two receptors that orchestrate the complex biological functions of tumor necrosis factor (TNF, also designed TNF-α). Accumulating experimental evidence suggests that TNFR2 plays an important role in renal disorders associated with acute cellular rejection and clear cell renal carcinoma but its exact role in these settings is still not completely understood. This papers reviews the factors that may mediate TNFR2 induction in acute cellular rejection and clear cell renal carcinoma and its contribution to these conditions and discusses its therapeutic implications. A greater understanding of the function of TNFR2 may lead to the development of new anti-TNF drugs. PMID:24350291

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    2005-01-01

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

  8. Acute effects of a winter air pollution episode on pulmonary function and respiratory symptoms of children

    SciTech Connect

    Hoek, G.; Brunekreef, B. )

    1993-09-01

    The acute respiratory effects of a wintertime air pollution episode were studied in a general population sample of 112 children who were 7-12 y of age and who lived in a nonurban community. Spirometry was performed on 6 d, with a fixed interval of 3 wk between successive tests. During an air pollution episode, an additional pulmonary function test was made. Acute respiratory symptoms of the children were noted in a diary. Ambient concentrations of sulfur dioxide, black smoke, particulate matter with an aerodynamic diameter less than 10 microns, and nitrogen dioxide were considered as exposure variables. The association of air pollution with pulmonary function and prevalence of acute respiratory symptoms was assessed by individual linear regression analysis and time series analysis, respectively. In February 1991, an air pollution episode occurred during which daily average sulfur dioxide concentrations were slightly above 100 micrograms/m3, and particulate matter (with an aerodynamic diameter of less than 10 microns) concentrations reached 174 micrograms/m3. During the episode, forced vital capacity, forced expiratory volume in 1 s, and maximal mid-expiratory flow were lower than on baseline tests. Significant negative associations were found between the concentration of sulfur dioxide, black smoke, and particulate matter with an aerodynamic diameter of less than 10 microns. No association between prevalence of acute respiratory symptoms and the concentration of these compounds was found.

  9. Two episodes of acute illness in a machine shop

    SciTech Connect

    Sinks, T.; Kerndt, P.R.; Wallingford, K.M.

    1989-08-01

    Following an explosion in a machine shop and temporary plant closure, on the day the plant returned to full operations a degreaser malfunctioned. Workers in the assembly room were exposed to trichloroethylene levels later estimated to have exceeded 220 ppm (OSHA PEL 100 ppm). The plant was evacuated and the degreaser taken out of operation. Blood testing for carbon monoxide (CO) on five employees found carboxyhemoglobin levels in excess of normal. The plant reopened the following morning. Over the next two weeks, 15 employees were seen by the plant nurses for similar complaints; although all returned to work, their carboxyhemoglobin levels, later found to be inaccurate, were reported by a local medical clinic to range from 13.7 to 20.0 percent. At the end of the second week, another outbreak of illness occurred, but carboxyhemoglobin, trichloroethylene, fluorocarbons, and methylene chloride were not elevated in all 17 persons tested; plant-wide monitoring for CO found no elevated levels. During the first outbreak of illness, cases were 2.26 times as likely to have entered the assembly room as noncases. During the second outbreak, cases were no more likely than noncases to have entered the assembly room. We believe the explosion, earlier toxic exposures and illness, and the misleading blood test results led to plant-wide anxiety which culminated in a collective stress reaction and the second outbreak. An open meeting with all employees, informing them of our findings, provided reassurance and no further episodes of illness occurred in this workforce.

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

    PubMed Central

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

    2015-01-01

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

  11. Renal allograft rejection: sonography and scintigraphy

    SciTech Connect

    Singh, A.; Cohen, W.N.

    1980-07-01

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

  12. 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

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

    SciTech Connect

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

    1985-05-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    1986-08-01

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

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

    SciTech Connect

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

    2015-04-10

    Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, and chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.

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

    PubMed

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

    2016-05-01

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

  18. Acute fatty liver of pregnancy: a clinical study of 12 episodes in 11 patients.

    PubMed Central

    Reyes, H; Sandoval, L; Wainstein, A; Ribalta, J; Donoso, S; Smok, G; Rosenberg, H; Meneses, M

    1994-01-01

    Twelve episodes of acute fatty liver of pregnancy (AFLP) were diagnosed in 11 patients during the past 18 years in a general hospital in Santiago, Chile, with a prevalence of 1 per 15,900 deliveries. Acute fatty liver of pregnancy started between the 31st and 38th weeks of pregnancy, with malaise, vomiting, jaundice, and lethargy as the main clinical manifestations. Polydipsia (in nine episodes) and skin pruritus (in seven episodes) were unusual clinical findings. In two patients, pruritus started two and four weeks before AFLP, suggesting that an intrahepatic cholestasis of pregnancy preceded AFLP in those patients. Considering the current prevalence of both diseases in Chile, their association should be considered fortuitous. In another patient, two consecutive pregnancies were affected by AFLP, raising to three the number of reported patients with recurrent AFLP. In 11 episodes, liver biopsies supported the diagnosis of AFLP by showing small and midsized vacuolar cytoplasmic transformation as the most prominent histopathological feature. Positive intracellular fat staining was found in the four samples analysed. Studies by electron microscopy showed megamitochondria with paracrystalline inclusions in four samples. All the mothers survived, but fetal mortality was 58.3%. Several extrahepatic complications delayed maternal recovery for up to four weeks after delivery. This study confirms an improvement in maternal prognosis in AFLP, discusses the possibility of an epidemiological association with intrahepatic cholestasis of pregnancy, and increases the number of patients reported with recurrent AFLP. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8307428

  19. Sudden psychotic episode probably due to meningoencephalitis and Chlamydia pneumoniae acute infection

    PubMed Central

    2005-01-01

    Background Since 9% to 20% of all cases of acute psychosis presenting to an Emergency Department (ED) are due to a general medical condition, cautious medical workup should be mandatory in such patients. Differential diagnosis must consider conditions as diverse as renal failure or CNS infection. Acute Chlamydia pneumoniae infection usually causes a self-limited respiratory syndrome. Rarely, acute neurological complications occur, with acute meningoencephalitis most frequently reported. Diagnosis requires a high level of suspicion and is difficult to confirm. Case report We describe a 22 year-old female Caucasian who, three days after a mild pharingitis, developed an acute psychosis with exuberant symptoms interspersed with periods of lucidity, in a background of normal consciousness and orientation. Initial medical and imagiological workup were inconclusive. After 20 days of unsuccessful treatment with antipsychotics she developed a high fever and was re-evaluated medically. Lumbar puncture revealed an inflammatory cerebrospinal fluid. MRI showed irregular thickening and nodularity of the lateral ventricles' lining. An anti-Chlamydia pneumoniae IgM antibody titter of 85 IU/ml was detected. All symptoms cleared after treatment with antibiotics and corticosteroids. Conclusion This is, to our knowledge, the first reported case of acute CP-associated meningoencephalitis manifesting as an acute psychotic episode. It illustrates the principle that non-organic psychiatric syndromes must remain a diagnosis of exclusion in first-time acute psychosis. PMID:16164756

  20. Acute stress and episodic memory retrieval: neurobiological mechanisms and behavioral consequences.

    PubMed

    Gagnon, Stephanie A; Wagner, Anthony D

    2016-04-01

    Episodic retrieval allows people to access memories from the past to guide current thoughts and decisions. In many real-world situations, retrieval occurs under conditions of acute stress, either elicited by the retrieval task or driven by other, unrelated concerns. Memory under such conditions may be hindered, as acute stress initiates a cascade of neuromodulatory changes that can impair episodic retrieval. Here, we review emerging evidence showing that dissociable stress systems interact over time, influencing neural function. In addition to the adverse effects of stress on hippocampal-dependent retrieval, we consider how stress biases attention and prefrontal cortical function, which could further affect controlled retrieval processes. Finally, we consider recent data indicating that stress at retrieval increases activity in a network of brain regions that enable reflexive, rapid responding to upcoming threats, while transiently taking offline regions supporting flexible, goal-directed thinking. Given the ubiquity of episodic memory retrieval in everyday life, it is critical to understand the theoretical and applied implications of acute stress. The present review highlights the progress that has been made, along with important open questions. PMID:26799371

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2008-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-08-01

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

  8. Effect of HIV infection on time to recovery from an acute manic episode

    PubMed Central

    Nakimuli-Mpungu, E; Mutamba, B; Nshemerirwe, S; Kiwuwa, MS; Musisi, S

    2010-01-01

    Introduction Understanding factors affecting the time to recovery from acute mania is critical in the management of manic syndromes. The aim of this study was to determine the effect of HIV infection on time to recovery from acute mania. Methods We performed a retrospective study in which medical charts of individuals who were treated for acute mania were reviewed. Survival analysis with Cox regression models were used to compare time to recovery from an acute manic episode between human immunodeficiency virus (HIV)-positive individuals and HIV-negative individuals. Results Median survival time was one week for HIV-positive individuals and more than four weeks for HIV-negative individuals (χ2 = 18.4, P value = 0.000). HIV infection was the only marginally significant independent predictor of survival probability on the acute admission ward (hazards ratio 2.87, P = 0.06). Conclusion Acute mania in HIV-infected persons responds faster to psychotropic drugs compared with that in HIV-negative persons. PMID:22096397

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

    PubMed

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

    2006-12-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Wojciechowski, David; Vincenti, Flavio

    2012-01-01

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

  13. Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

    PubMed Central

    Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

    2014-01-01

    Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

  16. Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine

    PubMed Central

    Lipton, Richard B.; Fanning, Kristina M.; Serrano, Daniel; Reed, Michael L.; Cady, Roger

    2015-01-01

    Objective: To test the hypothesis that ineffective acute treatment of episodic migraine (EM) is associated with an increased risk for the subsequent onset of chronic migraine (CM). Methods: In the American Migraine Prevalence and Prevention Study, respondents with EM in 2006 who completed the Migraine Treatment Optimization Questionnaire (mTOQ-4) and provided outcome data in 2007 were eligible for analyses. The mTOQ-4 is a validated questionnaire that assesses treatment efficacy based on 4 aspects of response to acute treatment. Total mTOQ-4 scores were used to define categories of acute treatment response: very poor, poor, moderate, and maximum treatment efficacy. Logistic regression models were used to examine the dichotomous outcome of transition from EM in 2006 to CM in 2007 as a function of mTOQ-4 category, adjusting for covariates. Results: Among 5,681 eligible study respondents with EM in 2006, 3.1% progressed to CM in 2007. Only 1.9% of the group with maximum treatment efficacy developed CM. Rates of new-onset CM increased in the moderate treatment efficacy (2.7%), poor treatment efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. In the fully adjusted model, the very poor treatment efficacy group had a more than 2-fold increased risk of new-onset CM (odds ratio = 2.55, 95% confidence interval 1.42–4.61) compared to the maximum treatment efficacy group. Conclusion: Inadequate acute treatment efficacy was associated with an increased risk of new-onset CM over the course of 1 year. Improving acute treatment outcomes might prevent new-onset CM, although reverse causality cannot be excluded. PMID:25609757

  17. Influence of acute tryptophan depletion on verbal declarative episodic memory in young adult females.

    PubMed

    Helmbold, K; Bubenzer, S; Dahmen, B; Eisert, A; Gaber, T J; Habel, U; Konrad, K; Herpertz-Dahlmann, B; Zepf, F D

    2013-11-01

    Diminished synthesis of the neurotransmitter serotonin (5-HT) in the brain has been linked to disturbed memory processes. The present study investigated the effects of diminished central nervous 5-HT synthesis as achieved by an acute dietary tryptophan depletion (ATD) on verbal declarative episodic memory in young women while controlling for the effects of female sex hormones. Eighteen healthy females (aged 20-31 years) participated in a within-subject repeated measures study, with two separate days of assessment spaced at least one individual menstrual cycle apart. On one day, participants were subjected to ATD, thus lowering central nervous 5-HT synthesis. The other day participants received a tryptophan-balanced amino acid load (BAL = control condition). The study was randomized, counterbalanced and double blind in terms of ATD/BAL administration. Measurements took place in the early follicular phase of the participants' menstrual cycle. Estrogen, FSH and LH levels were assessed at baseline. Verbal declarative episodic memory was assessed using a structured word-learning task. Short-term memory, as indexed by immediate recall, was reduced after ATD intake, whereas delayed recall and recognition after a 25-min delay did not show any differences after intake of ATD or BAL. In young women, verbal short-term memory function was more vulnerable to ATD than consolidation processes. In light of the possible interplay between female sex hormones and 5-HT, further studies comparing different menstrual cycle phases are needed. PMID:24072504

  18. Diagnostic pitfalls in a young Romanian ranger with an acute psychotic episode

    PubMed Central

    Nagy, Előd Ernő; Rácz, Attila; Urbán, Edit; Terhes, Gabriella; Berki, Timea; Horváth, Emőke; Georgescu, Anca M; Zaharia-Kézdi, Iringó E

    2016-01-01

    basis of the putative occupational risk, acute psychotic episode, and the success of antibiotic therapy, we registered this case as a late neuroborreliosis with atypical appearance. PMID:27217753

  19. Diagnostic pitfalls in a young Romanian ranger with an acute psychotic episode.

    PubMed

    Nagy, Előd Ernő; Rácz, Attila; Urbán, Edit; Terhes, Gabriella; Berki, Timea; Horváth, Emőke; Georgescu, Anca M; Zaharia-Kézdi, Iringó E

    2016-01-01

    of the putative occupational risk, acute psychotic episode, and the success of antibiotic therapy, we registered this case as a late neuroborreliosis with atypical appearance. PMID:27217753

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2008-02-01

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

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

    PubMed

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

    2010-08-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2013-01-01

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

  5. Changes in sleep, food intake, and activity levels during acute painful episodes in children with sickle cell disease.

    PubMed

    Jacob, Eufemia; Miaskowski, Christine; Savedra, Marilyn; Beyer, Judith E; Treadwell, Marsha; Styles, Lori

    2006-02-01

    As part of a larger study that examined pain experience, pain management, and pain outcomes among children with sickle cell disease, functional status (sleep, food intake, and activity levels) was examined during hospitalization for acute painful episodes. Children were asked to rate the amount of pain they experienced as well as the amount of time they slept, the amount of food they ate, and the amount of activity they had everyday. Children reported high levels of pain, which showed only a small decrease throughout hospitalization, and had disrupted sleep and wake patterns, decreased food intake, and decreased activity levels. Nurses need to routinely monitor functional status during acute painful episodes so that strategies to promote adequate sleep, food intake, and activity may be incorporated to minimize long-term negative outcomes in children with sickle cell disease. PMID:16428011

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Pan, Xudong; Sun, Lizhong

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-07-01

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

  10. Corneal Allograft Rejection: Immunopathogenesis to Therapeutics

    PubMed Central

    Qazi, Yureeda; Hamrah, Pedram

    2014-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Aetiology of Acute Febrile Episodes in Children Attending Korogwe District Hospital in North-Eastern Tanzania

    PubMed Central

    Mahende, Coline; Ngasala, Billy; Lusingu, John; Butichi, Allvan; Lushino, Paminus; Lemnge, Martha; Premji, Zul

    2014-01-01

    Introduction Although the burden of malaria in many parts of Tanzania has declined, the proportion of children with fever has not changed. This situation underscores the need to explore the possible causes of febrile episodes in patients presenting with symptoms at the Korogwe District Hospital (KDH). Methods A hospital based cross-sectional study was conducted at KDH, north-eastern Tanzania. Patients aged 2 to 59 months presenting at the outpatient department with an acute medical condition and fever (measured axillary temperature ≥37.5°C) were enrolled. Blood samples were examined for malaria parasites, human immunodeficiency virus (HIV) and bacterial infections. A urine culture was performed in selected cases to test for bacterial infection and a chest radiograph was requested if pneumonia was suspected. Diagnosis was based on both clinical and laboratory investigations. Results A total of 867 patients with a median age of 15.1 months (Interquartile range 8.6–29.9) were enrolled from January 2013 to October 2013. Respiratory tract infections were the leading clinical diagnosis with 406/867 (46.8%) of patients diagnosed with upper respiratory tract infection and 130/867 (15.0%) with pneumonia. Gastroenteritis was diagnosed in 184/867 (21.2%) of patients. Malaria infection was confirmed in 72/867 (8.3%) of patients. Bacterial infection in blood and urine accounted for 26/808 (3.2%) infections in the former, and 66/373 (17.7%) infections in the latter. HIV infection was confirmed in 10/824 (1.2%) of patients. Respiratory tract infections and gastroenteritis were frequent in patients under 36 months of age (87.3% and 91.3% respectively). Co-infections were seen in 221/867 (25.5%) of patients. The cause of fever was not identified in 65/867 (7.5%) of these patients. Conclusions The different proportions of infections found among febrile children reflect the causes of fever in the study area. These findings indicate the need to optimise patient management by

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

    PubMed

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

    2016-08-01

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

  16. 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

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

    PubMed

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

    2016-01-15

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

  18. Effects of antipsychotics on insight in schizophrenia: results from independent samples of first-episode and acutely relapsed patients.

    PubMed

    Misiak, Błażej; Frydecka, Dorota; Beszłej, Jan A; Moustafa, Ahmed A; Tybura, Piotr; Kucharska-Mazur, Jolanta; Samochowiec, Agnieszka; Bieńkowski, Przemysław; Samochowiec, Jerzy

    2016-07-01

    We aimed to investigate whether antipsychotics differentially impact insight and whether these effects appear because of improvement in psychopathological manifestation in 132 first-episode schizophrenia patients and 201 acutely relapsed schizophrenic patients, who were followed up for 12 weeks. Olanzapine and risperidone were administered to first-episode schizophrenia patients, whereas acutely relapsed schizophrenic patients were treated with olanzapine, perazine and ziprasidone. The Positive And Negative Syndrome Scale (PANSS) was used to assess psychopathology. Insight was assessed using the G12 item of PANSS. Unadjusted mixed-model regression analysis indicated a significant improvement in the PANSS G12 item score in both groups. There were no significant differences between distinct treatment subgroups of patients in terms of improvement in the PANSS G12 item score. After adjustment for the trajectories of changes in symptom dimensions, a decrease in the PANSS G12 item score was because of an improvement in positive, negative and excitement symptoms. A decrease in the PANSS G12 item score was also related to an increase in the severity of depressive symptomatology. Our results indicate that antipsychotics exert similar effects on insight in acute psychosis. These effects are likely because of an improvement in psychopathological manifestation. The improvement in insight might be related to the development of depressive symptoms. PMID:26836264

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

    PubMed

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

    2016-05-01

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

  20. Acute haemolytic episodes & fava bean consumption in G6PD deficient Iraqis.

    PubMed

    Yahya, H I; al-Allawi, N A

    1993-12-01

    The relation between fava bean ingestion and the occurrence of a haemolytic episode was studied in 102 glucose-6-phosphate dehydrogenate (G6PD) deficient Iraqi patients. None of the patients (mean age 12.8 yr) had a documented similar illness earlier, although all of them gave history of reported regular fava bean ingestion in the past. Further, none of the three patients who were rechallenged (2-3 months later) by the beans developed any clinical or laboratory evidence of haemolysis. The incidence of the haemolytic episodes was found to peak in April, while the fava bean season extends from February to June. This study thus does not support a causal relation between the bean ingestion and the haemolytic episodes in G6PD deficient Iraqis. Possibly, some other factor such as a viral infection may be involved. PMID:8132232

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2011-12-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2012-02-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2016-04-01

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

  9. Creating Learning Momentum through Overt Teaching Interactions during Real Acute Care Episodes

    ERIC Educational Resources Information Center

    Piquette, Dominique; Moulton, Carol-Anne; LeBlanc, Vicki R.

    2015-01-01

    Clinical supervisors fulfill a dual responsibility towards patient care and learning during clinical activities. Assuming such roles in today's clinical environments may be challenging. Acute care environments present unique learning opportunities for medical trainees, as well as specific challenges. The goal of this paper was to better understand…

  10. [Post-infectious functional gastrointestinal disorders: from the acute episode to chronicity].

    PubMed

    Mearin, Fermín; Balboa, Agustín

    2011-01-01

    Functional gastrointestinal disorders (FGID) form a major part of gastroenterology practice. Several studies have reported the development of post-infectious irritable bowel syndrome (PI-IBS) after acute gastroenteritis (AGE). Non-gastrointestinal (GI) infections may increase the risk of developing IBS. There are also data showing that a GI infection may trigger functional dyspepsia (PI-FD). The possible development of PI-IBS or PI-FD depends on factors related to both the infection and the host. Microinflammation has been found in patients with post-infectious FGID. Studies performed in animal models show that infection and acute inflammation permanently change gastrointestinal motility and sensitivity. The role of AGE in the development of FGID is important not only because this entity provides an excellent natural model for pathogenic study but also because it provides an opportunity for preventive action. PMID:21641686

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

    PubMed Central

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

    2011-01-01

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

  12. Age-related differences in pulmonary effects of acute and subchronic episodic ozone exposures in Brown Norway rats.

    PubMed

    Snow, Samantha J; Gordon, Christopher J; Bass, Virginia L; Schladweiler, Mette C; Ledbetter, Allen D; Jarema, Kimberly A; Phillips, Pamela M; Johnstone, Andrew F; Kodavanti, Urmila P

    2016-06-01

    Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25 and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects. Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers of pulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that adolescent and young adult animals are more susceptible to changes in ventilation and pulmonary injury/inflammation caused by acute and episodic O3 exposure. PMID:27097751

  13. Increased risk of severe vaso-occlusive episodes after initial acute chest syndrome in children with sickle cell anemia less than 4 years old: Sleep and asthma cohort.

    PubMed

    Vance, Leah D; Rodeghier, Mark; Cohen, Robyn T; Rosen, Carol L; Kirkham, Fenella J; Strunk, Robert C; DeBaun, Michael R

    2015-05-01

    Previous studies have shown that the highest incidence of acute chest syndrome (ACS) in sickle cell disease occurs in children <4 years old, and a history of ACS at this age is a risk factor for future ACS episodes. However, the interval associated with the highest risk of subsequent ACS or severe pain is not known. Through this mixed retrospective-prospective observational study, the Sleep and Asthma Cohort, we sought to determine the interval after an initial ACS episode during which the majority of children <4 years old are rehospitalized for ACS or severe pain. The cumulative prevalence of rehospitalization for ACS or severe pain within 6 months, 1 years, and 2 years was calculated for children with an initial ACS episode <4 years old and compared to children with an initial ACS episode ≥4 years old. A total of 44.8% and 55.2% of participants had an initial ACS episode <4 years and ≥4 years old (Range: 4-17.7 years), respectively. At 1 year following the initial ACS episode, children <4 years old had a significantly higher cumulative prevalence of rehospitalizations for ACS or pain as compared to children ≥4 years of age, 62.5 and 39.1%, respectively (P = 0.009). After initial ACS episodes, the majority of children <4 years old will be rehospitalized for ACS or severe pain within one year, suggesting the need for a therapeutic intervention for this high-risk group. PMID:25619382

  14. Parasite Specific Antibody Increase Induced by an Episode of Acute P. falciparum Uncomplicated Malaria

    PubMed Central

    Kaddumukasa, Mark; Lwanira, Catherine; Lugaajju, Allan; Katabira, Elly; Persson, Kristina E. M.; Wahlgren, Mats; Kironde, Fred

    2015-01-01

    Introduction There is no approved vaccine for malaria, and precisely how human antibody responses to malaria parasite components and potential vaccine molecules are developed and maintained remains poorly defined. In this study, antibody anamnestic or memory response elicited by a single episode of P. falciparum infection was investigated. Methods This study involved 362 malaria patients aged between 6 months to 60 years, of whom 19% were early-diagnosed people living with HIV/AIDS (PLWHA). On the day malaria was diagnosed and 42 days later, blood specimens were collected. Parasite density, CD4+ cells, and antibodies specific to synthetic peptides representing antigenic regions of the P. falciparum proteins GLURP, MSP3 and HRPII were measured. Results On the day of malaria diagnosis, Immunoglobulin (IgG) antibodies against GLURP, MSP3 and HRP II peptides were present in the blood of 75%, 41% and 60% of patients, respectively. 42 days later, the majority of patients had boosted their serum IgG antibody more than 1.2 fold. The increase in level of IgG antibody against the peptides was not affected by parasite density at diagnosis. The median CD4+ cell counts of PLWHAs and HIV negative individuals were not statistically different, and median post-infection increases in anti-peptide IgG were similar in both groups of patients. Conclusion In the majority (70%) of individuals, an infection of P. falciparum elicits at least 20% increase in level of anti-parasite IgG. This boost in anti-P. falciparum IgG is not affected by parasite density on the day of malaria diagnosis, or by HIV status. PMID:25906165

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

    PubMed Central

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

    1995-01-01

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

  16. A Pilot Study of Citalopram Treatment in Preventing Relapse of Depressive Episode after Acute Treatment

    PubMed Central

    Cheung, Amy; Levitt, Anthony; Cheng, Michael; Santor, Darcy; Kutcher, Stan; Dubo, Elyse; Jane Garland, E.; Weiss, Margaret; Kiss, Alex

    2016-01-01

    Purpose: To examine the benefit of continuation treatment with citalopram in adolescents 13 to 18 years of age with major depression using a multi-site randomized placebo controlled discontinuation design. Methods: Subjects with depression who responded to open label treatment with citalopram in 12-week acute phase were randomized to continued treatment with citalopram or placebo for 24 weeks. Results: Twenty five subjects were randomized to either continued treatment with citalopram (n = 12) versus placebo (n = 13). Seventy-five percent of subjects on citalopram (75%) remained well as compared to placebo (62%). Time to relapse was compared between groups using the log rank test and was not found to be significantly different (χ2(1) = 0.35, P = 0.55). A Cox proportional hazards model including drug assignment (hazard ratio (HR = 0.51, 95% CI 0.11 to 2.36, P = 0.39), gender (HR = 0.58, 95% CI 0.14 to 2.37, P = 0.44), or HAM-score at entry to continuation phase (HR = 1.33, 95% CI 0.90 to 1.95, P = 0.95) was not significant. Conclusion: Although we did not find statistically significant differences between citalopram and placebo, the findings suggest a possible benefit of continued treatment with citalopram over placebo. A larger clinical trial with adequate power is required to confirm or disconfirm these findings. PMID:27047552

  17. Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

    PubMed Central

    Manzanares, J; Julian, MD; Carrascosa, A

    2006-01-01

    Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances. Preclinical and clinical studies have suggested that they may result useful to treat diverse diseases, including those related with acute or chronic pain. The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains, conditions that are often refractory to therapy. Although the psychoactive effects of these substances have limited clinical progress to study cannabinoid actions in pain mechanisms, preclinical research is progressing rapidly. For example, CB1mediated suppression of mast cell activation responses, CB2-mediated indirect stimulation of opioid receptors located in primary afferent pathways, and the discovery of inhibitors for either the transporters or the enzymes degrading endocannabinoids, are recent findings that suggest new therapeutic approaches to avoid central nervous system side effects. In this review, we will examine promising indications of cannabinoid receptor agonists to alleviate acute and chronic pain episodes. Recently, Cannabis sativa extracts, containing known doses of tetrahydrocannabinol and cannabidiol, have granted approval in Canada for the relief of neuropathic pain in multiple sclerosis. Further double-blind placebo-controlled clinical trials are needed to evaluate the potential therapeutic effectiveness of various cannabinoid agonists-based medications for controlling different types of pain. PMID:18615144

  18. Episode of Familial Mediterranean Fever-Related Peritonitis in the Second Trimester of Pregnancy Followed by Acute Cholecystitis: Dilemmas and Pitfalls

    PubMed Central

    Kosmidis, Christophoros; Anthimidis, Georgios; Varsamis, Nikolaos; Makedou, Fotini; Georgakoudi, Eleni; Efthimiadis, Christophoros

    2016-01-01

    Patient: Female, 33 Final Diagnosis: Acute cholecystitis after Familial Mediterranean Fever-related peritonitis Symptoms: Acute abdomen • fever Medication: Colchicine Clinical Procedure: Laparoscopic cholecystectomy and adhesiolysis in the second trimester of pregnancy Specialty: Surgery Objective: Rare co-existance of disease or pathology Background: Differential diagnosis of acute abdomen in pregnant patients is one of the greatest challenges for the clinician. Occurrence of Familial Mediterranean Fever (FMF) paroxysm of peritonitis and acute cholecystitis during pregnancy is a unique clinical entity that leads to serious diagnostic and therapeutic dilemmas. Case Report: We present the case of a 33-year-old Armenian patient at 16 weeks’ gestational age with a history of FMF, who was admitted twice within 1 month with acute abdomen. The first episode was attributed to FMF and successfully treated conservatively with colchicine. The second episode was diagnosed as acute cholecystitis and led to emergent laparoscopic cholecystectomy and lysis of peritoneal adhesions from previous FMF attacks. The patient presented an uneventful postoperative clinical course and had a normal delivery of a healthy infant at the 39th week of gestation. Conclusions: Pregnant patients with acute abdomen should be evaluated with open mind. To the best of our knowledge, this is the first published report of the coexistence of 2 different causes of acute abdomen during pregnancy. Meticulous history and thorough physical, laboratory, and radiologic examination are the keys to reach a correct diagnosis. Treatment of pregnant patients with acute abdomen should be individualized. Administration of colchicine should be continued during conception, pregnancy, and lactation in patients with FMF history. Laparoscopic intervention in pregnant patients with surgical abdomen such as acute cholecystitis is the optimal method of treatment. PMID:26907752

  19. Lead concentrations in blood and milk from periparturient dairy heifers seven months after an episode of acute lead toxicosis

    SciTech Connect

    Galey, F.D.; Slenning, B.D.; Anderson, M.L.; Breneman, P.C.; Littlefield, E.S.; Melton, L.A.; Tracy, M.L. )

    1990-07-01

    In September 1988, 100 of 300 yearling dairy heifers developed blindness, tachypnea, foaming at the mouth, chewing, and facial fasciculations. Twenty-five animals died. Lead toxicosis was diagnosed based on the clinical signs and the presence of excessive concentrations of lead in whole blood, liver, kidney, and rumen contents of affected animals. The source of the lead was sudan grass silage that had been contaminated by soil that contained up to 77,000 mg/kg of lead. Lead concentrations were determined approximately 7 months after the acute episode of lead toxicosis. Whole blood and milk samples were obtained from heifers and a group of control cows 2 weeks prior to (blood only), at the time of, and 2 and 4 weeks after freshening. No lead was found in any of the milk samples (detection limit = 0.055 mg/liter). Animals that had been severely affected by lead toxicosis experienced a transient increase in whole blood lead concentrations at freshening that was not high enough to be considered toxic. No similar increases in blood lead were observed for control cows or heifers that had experienced milder toxicosis. These findings suggest that at parturition lead is mobilized into the blood of cattle previously exposed to excessive lead.

  20. Normalizing Rejection.

    PubMed

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

    2016-02-01

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

  1. Long-term non-invasive ventilation reduces readmissions in COPD patients with two or more episodes of acute hypercapnic respiratory failure

    PubMed Central

    Ankjærgaard, Kasper Linde; Maibom, Sophia Liff; Wilcke, Jon Torgny

    2016-01-01

    Background Chronic obstructive pulmonary disease (COPD) patients who have had an episode of acute hypercapnic respiratory failure (AHRF) have a large 1-year risk of death or readmission. Acute non-invasive ventilation (NIV) has been shown to be an effective treatment of AHRF; and long-term NIV (LTNIV) has been shown to be an effective treatment of chronic respiratory failure in stable hypercapnic COPD. We investigated the effects of LTNIV in a group of patients with severe, unstable COPD: frequent admissions and multiple previous episodes of AHRF treated with NIV. Methods We conducted a retrospective analysis of 20 COPD patients treated with LTNIV after two or more episodes of AHRF during 1 year. Results The mean number of AHRF episodes decreased from 2.44 in the year prior to LTNIV initiation to 0.44 in the year following (p<0.0001). The median number of admissions decreased from 5.19 to 1.88 (p=0.0092). Four patients (20%) died in 1 year. LTNIV tended to reduce arterial CO2. No changes were found in lung function. Conclusions LTNIV seems effective in reducing recurrent AHRF and readmissions in a highly select group of patients with severe, unstable COPD and frequent AHRF. PMID:27036658

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2003-01-01

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

  4. Increased risk of severe vaso-occlusive episodes after initial acute chest syndrome in children with sickle cell anemia less than 4 years old: Sleep and Asthma Cohort

    PubMed Central

    Vance, Leah D; Rodeghier, Mark; Cohen, Robyn T.; Rosen, Carol L.; Kirham, Fenella J.; Strunk, Robert C.; DeBaun, Michael R.

    2015-01-01

    Previous studies have shown that the highest incidence of acute chest syndrome (ACS) in sickle cell disease (SCD) occurs in children less than 4 years old, and a history of ACS at this age is a risk factor for future ACS episodes. However, the interval associated with the highest risk of subsequent ACS or severe pain is not known. Through this mixed retrospective-prospective observational study, the Sleep and Asthma Cohort, we sought to determine the interval after an initial ACS episode during which the majority of children <4 years old are re-hospitalized for ACS or severe pain. The cumulative prevalence of re-hospitalization for ACS or severe pain within 6 months, 1 years, and 2 years was calculated for children with an initial ACS episode <4 years old and compared to children with an initial ACS episode ≥4 years old. A total of 44.8% and 55.2% of participants had an initial ACS episode <4 years and ≥4 years old (Range: 4-17.7 years), respectively. At 1 year following the initial ACS episode, children <4 years old had a significantly higher cumulative prevalence of re-hospitalizations for ACS or pain as compared to children ≥4 years of age, 62.5% and 39.1%, respectively (P = 0.009). After initial ACS episodes, the majority of children <4 years old will be re-hospitalized for ACS or severe pain within one year, suggesting the need for a therapeutic intervention for this high-risk group. PMID:25619382

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

    PubMed Central

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

    2015-01-01

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

  6. The secondary prophylactic efficacy of beta-blocker after endoscopic gastric variceal obturation for first acute episode of gastric variceal bleeding

    PubMed Central

    Choi, Moon Han; Kim, Sang Gyune; Lee, Yun Nah; Seo, Yu Ri; Kim, Min Jin; Lee, Sae Hwan; Jeong, Soung Won; Jang, Jae Young; Kim, Hong Soo; Kim, Boo Sung

    2013-01-01

    Background/Aims The most appropriate treatment for acute gastric variceal bleeding (GVB) is currently endoscopic gastric variceal obturation (GVO) using Histoacryl®. However, the secondary prophylactic efficacy of beta-blocker (BB) after GVO for the first acute episode of GVB has not yet been established. The secondary prophylactic efficacy of BB after GVO for the first acute episode of GVB was evaluated in this study. Methods Ninety-three patients at Soonchunhyang University Hospital with acute GVB who received GVO using Histoacryl® were enrolled between June 2001 and March 2010. Among these, 42 patients underwent GVO alone (GVO group) and 51 patients underwent GVO with adjuvant BB therapy (GVO+BB group). This study was intended for patients in whom a desired heart rate was reached. The rates of rebleeding-free survival and overall survival were calculated for the two study groups using Kaplan-Meyer analysis and Cox's proportional-hazards model. Results The follow-up period after the initial eradication of gastric varices was 18.14±25.22 months (mean±SD). During the follow-up period, rebleeding occurred in 10 (23.8%) and 21 (41.2%) GVO and GVO+BB patients, respectively, and 39 patients died [23 (54.8%) in the GVO group and 16 (31.4%) in the GVO+BB group]. The mean rebleeding-free survival time did not differ significantly between the GVO and GVO+BB groups (65.40 and 37.40 months, respectively; P=0.774), whereas the mean overall survival time did differ (52.54 and 72.65 months, respectively; P=0.036). Conclusions Adjuvant BB therapy after GVO using Histoacryl® for the first acute episode of GVB could decrease the mortality rate relative to GVO alone. However, adjuvant BB therapy afforded no benefit for the secondary prevention of rebleeding in GV. PMID:24133666

  7. EFFECTS OF ACUTE AND WEEKLY EPISODIC EXPOSURES TO ANATOXIN-A ON THE MOTOR ACTIVITY OF RATS: COMPARISON WITH NICOTINE.

    EPA Science Inventory

    Anatoxin-a is a potent nicotinic cholinergic agonist, that is produced by many genera of cyanobacteria, and has caused several poisoning episodes of wildlife, livestock, and domestic animals. Cyanobacterial blooms and toxin exposures are likely to occur episodically as environmen...

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

    PubMed Central

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

    2013-01-01

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

  9. Episodic ozone exposure in adult and Senescent Brown Norway rats: Acute and delayed cardiovascular and thermoregulatory responses

    EPA Science Inventory

    Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O(3)) is more reflective of potential exposures occurri...

  10. Outpatient utilization patterns and quality outcomes after first acute episode of mental health hospitalization. Is some better than none, and is more service associated with better outcomes?

    PubMed

    Huff, E D

    2000-12-01

    Access to outpatient services within the first 30 days after an inpatient mental health episode may influence relapse risk. A retrospective cohort of 3,755 adult Medicaid mental health inpatients discharged from their first managed care acute episode of care from July 1, 1996, through May 20, 1998, were studied. Results showed patients' utilization of any psychotherapy (OR = .43), medication management (OR = .41), or diagnostic evaluation services (OR = .61), relative to no utilization, was associated with significantly lower 30-day readmission rates, and longer times in remission. However, patients receiving above the median total number of ambulatory services, or having contact with more providers showed significantly greater likelihood of 30-day readmission, and shorter time in remission. Findings heighten the need for the availability of timely risk-reducing mental health outpatient services, the continuity and risk of fragmentation of therapeutic relationships, as well as crisis planning before an inpatient discharge. PMID:11139870

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

    PubMed

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

    2016-07-01

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

  12. Emotional responses to interpersonal rejection.

    PubMed

    Leary, Mark R

    2015-12-01

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

  13. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-11-01

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

  17. Effects of cumulative stressful and acute variation episodes of farm climate conditions on late embryo/early fetal loss in high producing dairy cows

    NASA Astrophysics Data System (ADS)

    Santolaria, Pilar; López-Gatius, Fernando; García-Ispierto, Irina; Bech-Sàbat, Gregori; Angulo, Eduardo; Carretero, Teresa; Sánchez-Nadal, Jóse Antonio; Yániz, Jesus

    2010-01-01

    The aim of this study was to determine possible relationships between farm climate conditions, recorded from day 0 to day 40 post-artificial insemination (AI), and late embryo/early fetal loss in high producing dairy cows. Pregnancy was diagnosed by rectal ultrasonography between 28 and 34 days post-AI. Fetal loss was registered when a further 80- to 86-day diagnosis proved negative. Climate variables such as air temperature and relative humidity (RH) were monitored in the cubicles area for each 30-min period. Temperature-humidity indices (THI); cumulative stressful values and episodes of acute change (defined as the mean daily value 1.2 times higher or lower than the mean daily values of the 10 previous days) of the climate variables were calculated. The data were derived from 759 cows in one herd. A total of 692 pregnancies (91.2%) carried singletons and 67 (8.8%) carried twins. No triplets were recorded. Pregnancy loss was recorded in 6.7% (51/759) of pregnancies: 5.6% (39/692) in single and 17.9% (12/67) in twin pregnancies. Using logistic regression procedures, a one-unit increase in the daily cumulative number of hours for the THI values higher than 85 during days 11-20 of gestation caused a 1.57-fold increase in the pregnancy loss, whereas the likelihood of fetal loss increased by a factor of 1.16 for each additional episode of acute variation for the maximum THI values during gestation days 0-40. THI values higher than 85 and episodes of acute variation for the maximum THI values were only recorded during the warm and cool periods, respectively. The presence of twins led to a 3.98-fold increase in pregnancy loss. In conclusion, our findings show that cumulative stressful and episodes of acute variation of climatic conditions can compromise the success of gestation during both the cool and warm periods of the year. Twin pregnancy was confirmed as a main factor associated with pregnancy loss.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. Duration of Untreated Psychosis Is Associated with More Negative Schizophrenia Symptoms after Acute Treatment for First-Episode Psychosis

    ERIC Educational Resources Information Center

    Grano, Niklas; Lindsberg, Jenni; Karjalainen, Marjaana; Gronroos, Peter; Blomberg, Ari-Pekka

    2010-01-01

    Evidence of association between duration of untreated psychosis (DUP) and negative symptoms of schizophrenia in first-episode psychosis (FEP) patients is inconsistent in the recent literature. In the present study, DUP, schizophrenia symptoms, duration of medication, and diagnosis were obtained from hospital archives in a sample of FEP patients.…

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

    PubMed

    Bhatti, Adnan Bashir; Usman, Muhammad

    2015-01-01

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

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

    PubMed Central

    Usman, Muhammad

    2015-01-01

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

  3. Episodic Memories

    ERIC Educational Resources Information Center

    Conway, Martin A.

    2009-01-01

    An account of episodic memories is developed that focuses on the types of knowledge they represent, their properties, and the functions they might serve. It is proposed that episodic memories consist of "episodic elements," summary records of experience often in the form of visual images, associated to a "conceptual frame" that provides a…

  4. Acute and longer-term effects of risperidone in a case of first-episode catatonic schizophrenia.

    PubMed

    Kopala, L C; Caudle, C

    1998-01-01

    This case report documents the response of a young, first-episode, neuroleptic naive male with severe catatonic schizophrenia to the novel antipsychotic, risperidone. Initial assessments included the Positive and Negative Syndrome Scales, Global Assessment of Function and the Extrapyramidal Symptom Rating Scale. These were repeated at discharge from hospital and during a 3.5 year outpatient follow-up. Neuroimaging (computed tomography, magnetic resonance imaging and single photon emission tomography) along with electroencephalogram and laboratory examinations were completed. Response to risperidone was prompt, dramatic and sustained over the follow-up period. Possible neurochemical brain mechanisms resulting in catatonia and the role of serotonin/dopamine antagonists such as risperidone are discussed. No other literature on the effect of risperidone in the treatment of severe catatonic schizophrenia in a first-episode patient has been reported. PMID:10958259

  5. Episodic ozone exposure in adult and senescent Brown Norway rats: acute and delayed effect on heart rate, core temperature and motor activity.

    PubMed

    Gordon, C J; Johnstone, A F; Aydin, C; Phillips, P M; MacPhail, R C; Kodavanti, U P; Ledbetter, A D; Jarema, K A

    2014-06-01

    Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O₃) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O₃ (6 h/day of 1 ppm O₃ for 2 consecutive days/week for 13 weeks). Acute O₃ initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O₃. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O₃ exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O₃, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O₃ exposure. MA was elevated in adults but not senescent rats during recovery from O₃. Overall, acute effects of O₃, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O₃ in senescent rats may explain the relatively heightened physiological response to O₃ in younger rats. PMID:24779854

  6. A Pilot RCT of Psychodynamic Group Art Therapy for Patients in Acute Psychotic Episodes: Feasibility, Impact on Symptoms and Mentalising Capacity

    PubMed Central

    Montag, Christiane; Haase, Laura; Seidel, Dorothea; Bayerl, Martin; Gallinat, Jürgen; Herrmann, Uwe; Dannecker, Karin

    2014-01-01

    This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self-efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow-up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention-to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Acute renal failure induced by markedly decreased appetite secondary to a depressive episode after discontinuation of long-term lithium therapy in an elderly patient with bipolar disorder

    PubMed Central

    Okada, Akira

    2014-01-01

    Some elderly patients on chronic lithium therapy for bipolar disorder and their doctors may be faced with a therapeutic dilemma over whether or not to continue prescribing/taking lithium given their increased risk of reduced renal function. We present the case of a 78-year-old woman with bipolar disorder who discontinued lithium therapy due to increased risk factors for renal injury. After discontinuation, she experienced markedly decreased appetite secondary to a depressive episode, and developed acute renal failure, which subsequently progressed to a more advanced stage of chronic kidney disease. This case suggests that extreme care must be taken to prevent the recurrence of depression in elderly patients with bipolar disorder who discontinue lithium therapy, even when they had been emotionally stable for a long time while receiving lithium. Medications other than lithium for bipolar disorder may be needed at the time lithium therapy is discontinued. PMID:24835805

  11. Occurrence and predictors of recurrence after a first episode of acute venous thromboembolism: population-based Worcester Venous Thromboembolism Study.

    PubMed

    Huang, Wei; Goldberg, Robert J; Anderson, Frederick A; Cohen, Alexander T; Spencer, Frederick A

    2016-04-01

    Venous thromboembolism (VTE) has multiple risk factors and tends to recur. Despite the benefits of anticoagulation, the prevalence of, and case-fatality rate associated with, recurrent VTE remains a concern after an acute episode; it is particularly high during the acute treatment phase. We sought to quantify the magnitude, identify predictors, and develop risk score calculator of recurrence within 3 years after first-time VTE. This was a population-based surveillance study among residents of central Massachusetts (MA), USA, diagnosed with an acute first-time pulmonary embolism and/or lower-extremity deep vein thrombosis from 1999 to 2009 in hospital and ambulatory settings in all 12 central MA hospitals. Medical records were reviewed and validated. The 2989 study patients were followed for 5836 person-years [mean follow-up 23.4 (median 30) months]. Mean age was 64.3 years, 44 % were men, and 94 % were white. The cumulative incidence rate of recurrent VTE within 3 years after an index VTE was 15 % overall, and 25, 13, and 13 % among patients with active cancer, provoked, or unprovoked VTE, respectively. Multivariable regression indicated that active cancer, varicose vein stripping, and inferior vena cava filter placement were independent predictors of recurrence during both 3-month and 3-year follow-up. A risk score calculator was developed based on the 3-month prognostic model. In conclusion, the rate of VTE recurrence over 3 years of follow-up remained high. The risk score calculator may assist clinicians at the index encounter in determining the frequency of clinical surveillance and appropriate outpatient treatment of VTE during the acute treatment phase. PMID:26847621

  12. Treating humoral rejection after cardiac transplantation.

    PubMed

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

    2011-04-01

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

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

    PubMed

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

    2016-08-15

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

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

    PubMed Central

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

    2014-01-01

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

  15. Remote noninvasive allograft rejection monitoring for heart transplant recipients: study protocol for the novel evaluation with home electrocardiogram and remote transmission (NEW HEART) study

    PubMed Central

    2012-01-01

    Background Acute allograft rejection is a major cause of early mortality in the first year after heart transplantation in adults. Although endomyocardial biopsy (EMB) is not a perfect "gold standard" for a correct diagnosis of acute allograft rejection, it is considered the best available test and thus, is the current standard practice. Unfortunately, EMB is an invasive and costly procedure that is not without risk. Recent evidence suggests that acute allograft rejection causes delays in ventricular repolarization and thereby increases the cellular action potential duration resulting in a longer QT interval on the electrocardiogram (ECG). No prospective study to date has investigated whether such increases in the QT interval could provide early detection of acute allograft rejection. Therefore, in the Novel Evaluation With Home Electrocardiogram And Remote Transmission (NEW HEART) study, we plan to investigate the potential benefit of daily home QT interval monitoring to predict acute allograft rejection. Methods/design The NEW HEART study is a prospective, double-blind, multi-center descriptive research study. A sample of 325 adult heart transplant recipients will be recruited within six weeks of transplant from three sites in the United States. Subjects will receive the HeartView™ ECG recorder and its companion Internet Transmitter, which will transmit the subject's ECG to a Core Laboratory. Subjects will be instructed to record and transmit an ECG recording daily for 6 months. An increase in the QTC interval from the previous day of at least 25 ms that persists for 3 consecutive days will be considered abnormal. The number and grade of acute allograft rejection episodes, as well as all-cause mortality, will be collected for one year following transplant surgery. Discussion This study will provide "real world" prospective data to determine the sensitivity and specificity of QTC as an early non invasive marker of cellular rejection in transplant recipients

  16. Changes in brain regions associated with food-intake regulation, body mass and metabolic profiles during acute antipsychotic treatment in first-episode schizophrenia.

    PubMed

    Emsley, Robin; Asmal, Laila; Chiliza, Bonginkosi; du Plessis, Stefan; Carr, Jonathan; Kidd, Martin; Malhotra, Anil K; Vink, Matthijs; Kahn, Rene S

    2015-08-30

    We investigated whether morphological brain changes occurred in brain regions associated with body-weight homeostasis during acute antipsychotic treatment, and if so, whether they were related to changes in body mass and metabolic profile. Twenty-two antipsychotic-naive patients with first-episode schizophrenia received either risperidone long acting injection or flupenthixol decanoate over 13 weeks and were compared by structural MRI with 23 matched healthy volunteers at weeks 0, 4 and 13. Images were reconstructed using freesurfer fully-automated whole brain segmentation. The ventral diencephalon and prefrontal cortex were selected to represent the homeostatic and hedonic food intake regulatory systems respectively. Body mass was measured at weeks 0, 7 and 13 and fasting glucose and lipid profiles at weeks 0 and 13. Linear mixed effect models indicated significant group(⁎)time interactions for the ventral diencephalon volumes bilaterally. Ventral diencephalon volume reduction was strongly correlated bilaterally with body mass increase and HDL-cholesterol reductions, and unilaterally with blood glucose elevation. There were no significant changes in prefrontal cortical thickness. These findings implicate the ventral diencephalon, of which the hypothalamus is the main component, in the acute adipogenic and dyslipidaemic effects of antipsychotic medication. PMID:26184461

  17. Sensitization to Acute Procedural Pain in Pediatric Sickle Cell Disease: Modulation by Painful Vaso-occlusive Episodes, Age, and Endothelin-1

    PubMed Central

    Schlenz, Alyssa M.; McClellan, Catherine B.; Mark, Teresa R.M.; McKelvy, Alvin D.; Puffer, Eve; Roberts, Carla W.; Sweitzer, Sarah M.; Schatz, Jeffrey C.

    2012-01-01

    The impact of pain early in life is a salient issue for sickle cell disease (SCD), a genetic condition characterized by painful vaso-occlusive episodes (VOEs) that can begin in the first year of life and persist into adulthood. This study examined the effects of age and pain history (age of onset and frequency of recent VOEs) on acute procedural pain in children with SCD. Endothelin-1, a vaso-active peptide released during VOEs and acute tissue injury, and its precursor, Big Endothelin, were explored as markers of pain sensitization and vaso-occlusion. Sixty-one children with SCD (ages 2 to 18) underwent venipuncture at routine health visits. Procedural pain was assessed via child- and caregiver-reports and observational distress. Pain history was assessed using retrospective chart review. Three primary results were found: 1) younger age was associated with greater procedural pain across pain outcomes, 2) higher frequency of VOEs was associated with greater procedural pain based on observational distress (regardless of age), and 3) age was found to moderate the relationship between VOEs and procedural pain for child-reported pain and observational distress for children five years of age and older. Associations between the endothelin variables and pain prior to venipuncture were also observed. PMID:22633685

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

    PubMed

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

    2016-06-01

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

  19. High Mean Fluorescence Intensity Donor-Specific Anti-HLA Antibodies Associated With Chronic Rejection Postliver Transplant

    PubMed Central

    O’Leary, J. G.; Kaneku, H.; Susskind, B. M.; Jennings, L. W.; Neri, M. A.; Davis, G. L.; Klintmalm, G. B.; Terasaki, P. I.

    2015-01-01

    In contrast to kidney transplantation where donorspecific anti-HLA antibodies (DSA) negatively impact graft survival, correlation of DSA with clinical outcomes in patients after orthotopic liver transplantation (OLT) has not been clearly established. We hypothesized that DSA are present in patients who develop chronic rejection after OLT. Prospectively collected serial serum samples on 39 primary OLT patients with biopsy-proven chronic rejection and 39 comparator patients were blinded and analyzed for DSA using LABScreen single antigen beads test, where a 1000 mean fluorescence value was considered positive. In study patients, the median graft survival was 15 months, 74% received ≥ one retransplant, 20% remain alive and 87% had ≥ one episode of acute rejection. This is in contrast to comparator patients where 69% remain alive, and no patient needed retransplant or experienced rejection. Thirty-six chronic rejection patients (92%) and 24 (61%) comparator patients had DSA (p = 0.003). Chronic rejection versus comparator patients had higher mean fluorescence intensity (MFI) DSA. Although a further study with larger numbers of patients is needed to identify clinically significant thresholds, there is an association of high-MFI DSA with chronic rejection after OLT. PMID:21672151

  20. Effect of a Simple Information Booklet on Pain Persistence after an Acute Episode of Low Back Pain: A Non-Randomized Trial in a Primary Care Setting

    PubMed Central

    Coudeyre, Emmanuel; Baron, Gabriel; Coriat, Fernand; Brin, Sylvie; Revel, Michel; Poiraudeau, Serge

    2007-01-01

    Objective Mass-media campaigns have been known to modify the outcome of low back pain (LBP). We assessed the impact on outcome of standardized written information on LBP given to patients with acute LBP. Methods Design: A 3-month pragmatic, multicenter controlled trial with geographic stratification. Setting: Primary care practice in France. Participants: 2752 patients with acute LBP. Intervention: An advice book on LBP (the “back book”). Main outcome measures: The main outcome measure was persistence of LBP three months after baseline evaluation. Results 2337 (85%) patients were assessed at follow-up and 12.4% of participants reported persistent LBP. The absolute risk reduction of reporting persistent back pain in the intervention group was 3.6% lower than in the control group (10.5% vs. 14.1%; 95% confidence interval [−6.3% ; −1.0%]; p value adjusted for cluster effect = 0.01). Patients in the intervention group were more satisfied than those in the control group with the information they received about physical activities, when to consult their physician, and how to prevent a new episode of LBP. However, the number of patients who had taken sick leave was similar, as was the mean sick-leave duration, in both arms, and, among patients with persistent pain at follow-up, the intervention and control groups did not differ in disability or fear-avoidance beliefs. Conclusions The level of improvement of an information booklet is modest, but the cost and complexity of the intervention is minimal. Therefore, the implications and generalizability of this intervention are substantial. Trial Registration ClinicalTrials.gov NCT00343057 PMID:17684553

  1. Long-term efficacy of atorvastatin in allograft rejection following renal transplantation: A randomized clinical trial.

    PubMed

    Amirzargar, Mohammad A; Hosseini, Arsha Tafreshi; Gholiaf, Mahmood; Dadras, Farahnaz; Khoshjoo, Farhad

    2015-09-01

    Statins are a class of drug that can efficiently reduce the level of low-density lipoprotein (LDL) as well as increase the LDL receptors. Several non-lipid-lowering effects of this type of drug have been described. It is reported that they have an influence in preventing graft rejection, especially of the acute type. In this study, patients with end-stage renal disease and candidates for kidney transplantation were divided into two groups. Group A (intervention group) received atorvastatin for two weeks prior to their transplant surgery while group B (control group) received placebo. The lipid profile was tested (triglycerides, cholesterol, LDL) in all patients two weeks before the transplantation. After transplantation, drug use was stopped. We also checked the LDL serum levels in patients with raised lipid levels (LDL >100) every two weeks. After this period, the serum lipid levels were checked monthly up to six months. Hyperlipidemia, when present, was controlled by fibrates. Concerning the rejection episodes, there was no significant difference between the two groups. In group A (13 men and nine women), three (14.3%) cases of rejection were observed whereas four (21.3%) cases of rejection were seen in group B (11 men and 10 women) (P = 0.5). Within group A, five (22.7%) cases of delayed graft function were found while four (19%) similar cases were observed in group B (P = 0.7). There was no statistically significant difference concerning delayed graft function between the two groups. Despite all the mechanisms attributed to the probable anti-rejection properties of statins, we found no significant correlation with the administration of these drugs before transplantation and the protection against graft rejection episodes. PMID:26354567

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

    PubMed Central

    2012-01-01

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

  3. Oak Forest Responses to Episodic-Seasonal-Drought, Chronic Multi-year Precipitation Change and Acute Drought Manipulations in a Region With Deep Soils and High Precipitation

    NASA Astrophysics Data System (ADS)

    Hanson, Paul J.; Wullschleger, Stan D.; Todd, Donald E.; Auge, Robert M.; Froberg, Mats; Johnson, Dale W.

    2010-05-01

    Implications of episodic-seasonal drought (extremely dry late summers), chronic multi-year precipitation manipulations (±33 percent over 12 years) and acute drought (-100 percent over 3 years) were evaluated for the response of vegetation and biogeochemical cycles for an upland-oak forest. The Quercus-Acer forest is located in eastern Tennessee on deep acidic soils with mean annual temperatures of 14.2 °C and abundant precipitation (1352 mm y-1). The multi-year observations and chronic manipulations were conducted from 1993 through 2005 using understory throughfall collection troughs and redistribution gutters and pipes. Acute manipulations of dominant canopy trees (Quercus prinus; Liriodendron tulipifera) were conducted from 2003 through 2005 using full understory tents. Regional and severe late-summer droughts were produced reduced stand water use and photosynthetic carbon gain as expected. Likewise, seedlings and saplings exhibited reduced survival and cumulative growth reductions. Conversely, multi-year chronic increases or decreases in precipitation and associated soil water deficits did not reduce large tree basal area growth for the tree species present. The resilience of canopy trees to chronic-change was the result of a disconnect between carbon allocation to tree growth (an early-season phenomenon) and late-season drought occurrence. Acute precipitation exclusion from the largest canopy trees also produced limited physiological responses and minimal cumulative growth reductions. Lateral root water sources were removed through trenching and could not explain the lack of response to extreme soil drying. Therefore, deep rooting the primary mechanism for large-tree resilience to severe drought. Extensive trench-based assessments of rooting depth suggested that ‘deep' water supplies were being obtained from limited numbers of deep fine roots. Observations of carbon stocks in organic horizons demonstrated accumulation with precipitation reductions and

  4. Antibody-Mediated Lung Transplant Rejection

    PubMed Central

    Hachem, Ramsey

    2012-01-01

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

  5. Thallium kinetics in rat cardiac transplant rejection

    SciTech Connect

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

    1988-04-01

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

  6. Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients

    PubMed Central

    Maloney, Ann E; Sikich, Linmarie

    2010-01-01

    Background Severe and persistent mental illnesses in children and adolescents, such as early- onset schizophrenia spectrum (EOSS) disorders and pediatric bipolar disorder (pedBP), are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP. Methods PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined. Results Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare. Conclusions The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine-treated youth focused attention on the potential long-term risks of atypical antipsychotics in youth. PMID:21127693

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

    PubMed

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

    1996-08-01

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

  8. Effect of Home-Based Telemonitoring Using Mobile Phone Technology on the Outcome of Heart Failure Patients After an Episode of Acute Decompensation: Randomized Controlled Trial

    PubMed Central

    Scherr, Daniel; Kastner, Peter; Kollmann, Alexander; Hallas, Andreas; Auer, Johann; Krappinger, Heinz; Schuchlenz, Herwig; Stark, Gerhard; Grander, Wilhelm; Jakl, Gabriele; Schreier, Guenter

    2009-01-01

    Background Telemonitoring of patients with chronic heart failure (CHF) is an emerging concept to detect early warning signs of impending acute decompensation in order to prevent hospitalization. Objective The goal of the MOBIle TELemonitoring in Heart Failure Patients Study (MOBITEL) was to evaluate the impact of home-based telemonitoring using Internet and mobile phone technology on the outcome of heart failure patients after an episode of acute decompensation. Methods Patients were randomly allocated to pharmacological treatment (control group) or to pharmacological treatment with telemedical surveillance for 6 months (tele group). Patients randomized into the tele group were equipped with mobile phone–based patient terminals for data acquisition and data transmission to the monitoring center. Study physicians had continuous access to the data via a secure Web portal. If transmitted values went outside individually adjustable borders, study physicians were sent an email alert. Primary endpoint was hospitalization for worsening CHF or death from cardiovascular cause. Results The study was stopped after randomization of 120 patients (85 male, 35 female); median age was 66 years (IQR 62-72). The control group comprised 54 patients (39 male, 15 female) with a median age of 67 years (IQR 61-72), and the tele group included 54 patients (40 male, 14 female) with a median age of 65 years (IQR 62-72). There was no significant difference between groups with regard to baseline characteristics. Twelve tele group patients were unable to begin data transmission due to the inability of these patients to properly operate the mobile phone (“never beginners”). Four patients did not finish the study due to personal reasons. Intention-to-treat analysis at study end indicated that 18 control group patients (33%) reached the primary endpoint (1 death, 17 hospitalizations), compared with 11 tele group patients (17%, 0 deaths, 11 hospitalizations; relative risk reduction 50%, 95

  9. The bacterial lysate Lantigen B reduces the number of acute episodes in patients with recurrent infections of the respiratory tract: the results of a double blind, placebo controlled, multicenter clinical trial.

    PubMed

    Braido, Fulvio; Melioli, Giovanni; Candoli, Piero; Cavalot, Andrea; Di Gioacchino, Mario; Ferrero, Vittorio; Incorvaia, Cristoforo; Mereu, Carlo; Ridolo, Erminia; Rolla, Giovanni; Rossi, Oliviero; Savi, Eleonora; Tubino, Libero; Reggiardo, Giorgio; Baiardini, Ilaria; di Marco, Eddi; Rinaldi, Gilberto; Canonica, Giorgio Walter; Accorsi, Carlo; Bossilino, Claudia; Bonzano, Laura; DiLizia, Michela; Fedrighini, Barbara; Garelli, Valentina; Gerace, Vincenzo; Maniscalco, Sara; Massaro, Ilaria; Messi, Alessandro; Milanese, Manlio; Peveri, Silvia; Penno, Arminio; Pizzimenti, Stefano; Pozzo, Tiziana; Raie, Alberto; Regina, Sergio; Sclifò, Francesca

    2014-12-01

    Studies in the 1970s and 1980s reported that bacterial lysates (BL) had a prophylactic effect on recurrent respiratory tract infections (RRTI). However, controlled clinical study procedures have evolved substantially since then. We performed a trial using updated methods to evaluate the efficacy of Lantigen B®, a chemical BL. This double blind, placebo controlled, multi-center clinical trial had the primary objective of assessing the capacity of Lantigen B to significantly reduce the total number of infectious episodes in patients with RRTI. Secondary aims were the RRTI duration, the frequency and the severity of the acute episodes, the use of drugs and the number of missed workdays. In the subgroup of allergic patients with RRTI, the number of allergic episodes (AE) and the use of anti-allergic drugs were also evaluated. One hundred and sixty patients, 79 allocated to the treated group (TG) and 81 to the placebo group (PG), were enrolled; 30 were lost during the study and 120 (79 females and 38 males) were evaluated. The PG had 1.43 episodes in the 8-months of follow-up while the TG had 0.86 episodes (p=0.036). A similar result was observed in the allergic patients (1.80 and 0.86 episodes for the PG and the TG, respectively, p=0.047). The use of antibiotics was reduced (mean 1.24 and 2.83 days of treatment for the TG and the PG). Logistic regression analysis indicated that the estimated risk of needing antibiotics and NSAIDs was reduced by 52.1 and 30.6%, respectively. With regard to the number of AE, no significant difference was observed between the two groups, but bronchodilators, antihistamines and local corticosteroids were reduced by 25.7%, 56.2% and 41.6%, respectively, in the TG. Lantigen B significantly reduced the number of infectious episodes in patients with RRTI. This finding suggests a first line use of this drug for the prophylaxis of infectious episodes in these patients. PMID:25445613

  10. Clinical presentation, risk factors and treatment outcomes of first allograft rejection after penetrating keratoplasty in early and late postoperative period

    PubMed Central

    Perera, C; Jhanji, V; Lamoureux, E; Pollock, G; Favilla, I; Vajpayee, R B

    2012-01-01

    Purpose Corneal graft rejection is the most common reason for the failure of an allograft corneal transplant. We undertook this study to identify and compare risk factors and treatment outcomes for early and late corneal graft rejections after optical penetrating keratoplasty. Methods A retrospective case file analysis of 880 primary penetrating keratoplasties was performed at a tertiary ophthalmic care centre. Patients were divided into early rejectors (rejection episode within 6 months postoperatively) and late rejectors (rejection episode after 6 months postoperatively). Main parameters evaluated were demographics, preoperative diagnosis and clinical signs, donor tissue details, surgical technique, details of rejection episode, treatment, and outcome information. Results A total of 156 patients with rejection episodes were identified. Of these, 42 (26.9%) patients experienced early rejection episodes and 114 (73.1%) patients experienced late rejection episodes. Preoperative donor and recipient characteristics, surgical technique, and clinical presentation of graft rejection were found to be similar between both groups after a Bonferroni correction was applied (P>0.005). Treatment outcomes of graft rejections were not significantly different (P=0.46) between early and late rejectors, with 83% of patients responding to rejection treatment (80% early rejectors; 85% late rejectors). Conclusion Patients with early and late graft rejection have similar characteristics and both groups respond to treatment equally. PMID:22344190

  11. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection.

    PubMed

    Locke, J E; Magro, C M; Singer, A L; Segev, D L; Haas, M; Hillel, A T; King, K E; Kraus, E; Lees, L M; Melancon, J K; Stewart, Z A; Warren, D S; Zachary, A A; Montgomery, R A

    2009-01-01

    Desensitized patients are at high risk of developing acute antibody-mediated rejection (AMR). In most cases, the rejection episodes are mild and respond to a short course of plasmapheresis (PP) / low-dose IVIg treatment. However, a subset of patients experience severe AMR associated with sudden onset oliguria. We previously described the utility of emergent splenectomy in rescuing allografts in patients with this type of severe AMR. However, not all patients are good candidates for splenectomy. Here we present a single case in which eculizumab, a complement protein C5 antibody that inhibits the formation of the membrane attack complex (MAC), was used combined with PP/IVIg to salvage a kidney undergoing severe AMR. We show a marked decrease in C5b-C9 (MAC) complex deposition in the kidney after the administration of eculizumab. PMID:18976298

  12. Cellular and Functional Imaging of Cardiac Transplant Rejection

    PubMed Central

    Wu, Yijen L.; Ye, Qing

    2011-01-01

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

  13. Precision Subtypes of T Cell-Mediated Rejection Identified by Molecular Profiles

    PubMed Central

    Kadota, Paul Ostrom; Hajjiri, Zahraa; Finn, Patricia W.; Perkins, David L.

    2015-01-01

    Among kidney transplant recipients, the treatment of choice for acute T cell-mediated rejection (TCMR) with pulse steroids or antibody protocols has variable outcomes. Some rejection episodes are resistant to an initial steroid pulse, but respond to subsequent antibody protocols. The biological mechanisms causing the different therapeutic responses are not currently understood. Histological examination of the renal allograft is considered the gold standard in the diagnosis of acute rejection. The Banff Classification System was established to standardize the histopathological diagnosis and to direct therapy. Although widely used, it shows variability among pathologists and lacks criteria to guide precision individualized therapy. The analysis of the transcriptome in allograft biopsies, which we analyzed in this study, provides a strategy to develop molecular diagnoses that would have increased diagnostic precision and assist the development of individualized treatment. Our hypothesis is that the histological classification of TCMR contains multiple subtypes of rejection. Using R language algorithms to determine statistical significance, multidimensional scaling, and hierarchical, we analyzed differential gene expression based on microarray data from biopsies classified as TCMR. Next, we identified KEGG functions, protein–protein interaction networks, gene regulatory networks, and predicted therapeutic targets using the integrated database ConsesnsusPathDB (CPDB). Based on our analysis, two distinct clusters of biopsies termed TCMR01 and TCMR02 were identified. Despite having the same Banff classification, we identified 1933 differentially expressed genes between the two clusters. These genes were further divided into three major groups: a core group contained within both the TCMR01 and TCMR02 subtypes, as well as genes unique to TCMR01 or TCMR02. The subtypes of TCMR utilized different biological pathways, different regulatory networks and were predicted to

  14. Haptoglobin Enhances Cardiac Transplant Rejection

    PubMed Central

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

    2015-01-01

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

  15. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients

    PubMed Central

    Pike, Rebecca; Thomas, Niclas; Workman, Sarita; Ambrose, Lyn; Guzman, David; Sivakumaran, Shivajanani; Johnson, Margaret; Thorburn, Douglas; Harber, Mark; Chain, Benny; Stauss, Hans J.

    2016-01-01

    We tested whether multi-parameter immune phenotyping before or after renal ­transplantation can predict the risk of rejection episodes. Blood samples collected before and weekly for 3 months after transplantation were analyzed by multi-parameter flow cytometry to define 52 T cell and 13 innate lymphocyte subsets in each sample, producing more than 11,000 data points that defined the immune status of the 28 patients included in this study. Principle component analysis suggested that the patients with histologically confirmed rejection episodes segregated from those without rejection. Protein death 1 (PD-1)-expressing subpopulations of regulatory and conventional T cells had the greatest influence on the principal component segregation. We constructed a statistical tool to predict rejection using a support vector machine algorithm. The algorithm correctly identified 7 out of 9 patients with rejection, and 14 out of 17 patients without rejection. The immune profile before transplantation was most accurate in determining the risk of rejection, while changes of immune parameters after transplantation were less accurate in discriminating rejection from non-rejection. The data indicate that pretransplant immune subset analysis has the potential to identify patients at risk of developing rejection episodes, and suggests that the proportion of PD1-expressing T cell subsets may be a key indicator of rejection risk. PMID:27148254

  16. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients.

    PubMed

    Pike, Rebecca; Thomas, Niclas; Workman, Sarita; Ambrose, Lyn; Guzman, David; Sivakumaran, Shivajanani; Johnson, Margaret; Thorburn, Douglas; Harber, Mark; Chain, Benny; Stauss, Hans J

    2016-01-01

    We tested whether multi-parameter immune phenotyping before or after renal -transplantation can predict the risk of rejection episodes. Blood samples collected before and weekly for 3 months after transplantation were analyzed by multi-parameter flow cytometry to define 52 T cell and 13 innate lymphocyte subsets in each sample, producing more than 11,000 data points that defined the immune status of the 28 patients included in this study. Principle component analysis suggested that the patients with histologically confirmed rejection episodes segregated from those without rejection. Protein death 1 (PD-1)-expressing subpopulations of regulatory and conventional T cells had the greatest influence on the principal component segregation. We constructed a statistical tool to predict rejection using a support vector machine algorithm. The algorithm correctly identified 7 out of 9 patients with rejection, and 14 out of 17 patients without rejection. The immune profile before transplantation was most accurate in determining the risk of rejection, while changes of immune parameters after transplantation were less accurate in discriminating rejection from non-rejection. The data indicate that pretransplant immune subset analysis has the potential to identify patients at risk of developing rejection episodes, and suggests that the proportion of PD1-expressing T cell subsets may be a key indicator of rejection risk. PMID:27148254

  17. Association of urodynamic findings in new onset multiple sclerosis with subsequent occurrence of urinary symptoms and acute episode of disease in females

    PubMed Central

    Tadayyon, Farhad; Etemadifar, Masoud; Bzeih, Hussein; Zargham, Mahtab; Nouri-Mahdavi, Kia; Akbari, Mojtaba; Tadayyon, Borna

    2012-01-01

    Background: The aim of the study was to determine the relative frequency of abnormal urodynamic findings in new multiple sclerosis (MS) cases without micturition complaints and to find its correlation with the number of MS plaques on magnetic resonance imaging (MRI), urinary tract involvement and the number of disease episodes. Methods: In this prospective study, 50 new female case of multiple sclerosis were enrolled. Age, urodynamic findings, micturition complaints and number of plaques on MRI were recorded on admission. Occurrence of urinary symptoms and number of episodes of the disease were recorded every three months during one-year follow-up. Results: The mean patients’ age was 32.4 ± 7.2 years and all patients were female. Of the 50 patients, 19 (38%) had a normal urodynamic test and 31 (62%) had abnormal urodynamic findings at the beginning of the study. The occurrence of micturition complaints during follow-up in patients with abnormal urodynamic findings (94%) was significantly higher (p < 0.0001) than patients with normal urodynamic findings (37%). In addition, the number of plaques on MRI at the beginning of the study in patients with abnormal urodynamic finding was significantly higher (p < 0.004) compared to patients with a normal urodynamic study. The number of episodes during follow-up was not statistically different between patients with normal and abnormal urodynamic findings (p = 0.46). Conclusions: According to this study, 62% of all new MS patients had an abnormal urodynamic test. This is a considerable proportion of patients and it seems urodynamic studies can be used when MS is first diagnosed. PMID:23267402

  18. Development of cytotoxic antibodies following renal allograft transplantation is associated with reduced graft survival due to chronic vascular rejection.

    PubMed

    Davenport, A; Younie, M E; Parsons, J E; Klouda, P T

    1994-01-01

    We prospectively followed 64 patients who had had no cytotoxic antibodies prior to first cadaveric renal allograft transplantation for post-transplant antibodies. During a mean follow-up period of 62 months (range 45-92) cytotoxic antibodies developed in 36 patients (56%). Sixteen grafts were lost due to chronic vascular rejection in the group of patients who developed antibodies compared to two in those who remained antibody negative, P < 0.01. Renal function was worse in the antibody-positive group, median serum creatinine 215 mumol/l (131-256) (interquartile range) versus 111 mumol/l (98-127) in the antibody-negative group, P = 0.002, and creatinine clearance 39 ml/min (25-55) versus 90 ml/min (55-104), P < 0.001. There were no significant differences in immunosuppressive protocol, HLA-mismatching, blood transfusion history, the number of acute rejection episodes, mean arterial blood pressure, or proteinuria between the groups. The presence of cytotoxic antibodies predated the classical manifestations of chronic vascular rejection. This suggests that humoral mechanisms may play a role in the development of chronic vascular rejection. PMID:7816298

  19. Codominant Role of Interferon-γ- and Interleukin-17-Producing T Cells During Rejection in Full Facial Transplant Recipients.

    PubMed

    Borges, T J; O'Malley, J T; Wo, L; Murakami, N; Smith, B; Azzi, J; Tripathi, S; Lane, J D; Bueno, E M; Clark, R A; Tullius, S G; Chandraker, A; Lian, C G; Murphy, G F; Strom, T B; Pomahac, B; Najafian, N; Riella, L V

    2016-07-01

    Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean follow-up of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-γ/interleukin-17-producing cells in peripheral blood and in the allograft's skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17-mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development. PMID:26749226

  20. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning.

    PubMed

    Masmas, Tania N; Petersen, Søren L; Madsen, Hans O; Ryder, Lars P; Kornblit, Brian; Svejgaard, Arne; Andersen, Pernille; Dickmeiss, Ebbe; Vindeløv, Lars L

    2008-07-01

    Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without rejection. Retransplantation was performed with increased TBI conditioning for all patients, and with increased mycophenolate mofetil doses for recipients with HLA-identical sibling donors. No known pretransplantation risk factors were confirmed in this study. Rejection episodes were unevenly distributed over time. The storage temperature of the apheresis products was identified as a risk factor for rejection. Storage of the apheresis products at 5 degrees C diminished the risk of rejection. Low donor T cell chimerism at Day +14 significantly increased the risk of rejection. Seven patients were retransplanted. All but one engrafted successfully, but with decreased OS and PFS. Two patients received pentostatin infusion prior to donor lymphocyte infusions in unsuccessful attempts at reversing rejection. Storage temperature and donor chimerism had a significant effect on rejection. Following rejection, patients are at greater risk of dying from infections and progression/relapse of their malignancy. Retransplantation is feasible and well tolerated after HCT with nonmyeloablative conditioning and should be performed without delay in patients with imminent and manifest graft rejection. PMID:18383319

  1. Countering Rejection Anxiety.

    ERIC Educational Resources Information Center

    Hanselman, Peggy Riley

    1989-01-01

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

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

    PubMed

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

    2016-01-01

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

  3. Acute and Long-Term Response of Dopamine Nigrostriatal Synapses to a Single Low Dose Episode of 3-Nitropropionic Acid-Mediated Chemical Hypoxia

    PubMed Central

    Crawford, Cynthia A.; Akopian, Garnik; Ring, Justin; Jakowec, Michael W.; Petzinger, Giselle M.; Andersen, Julie K.; Vittozzi-Wong, Philip; Wang, Kristie; Farley, Cristal M.; Charntikov, Sergios; Mitroi, Danut; Beal, M. Flint; Chow, Robert; Walsh, John P.

    2010-01-01

    The goal of the present investigation was to determine the persistence of striatal dopaminergic dysfunction after a mild chemically-induced hypoxic event in Fisher 344 rats. To this end, we gave a single injection of the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP; 16.5 mg/kg, i.p.) to 2 month old male F344 rats and measured various indices of striatal dopaminergic functioning and lipid peroxidation over a 3 month span. Separate groups of rats were used to measure rod walking, evoked dopamine (DA) release, DA content, MDA accumulation, DA receptor binding, and tyrosine hydroxylase activity. The results showed that 3-NP exposure reduced most measures of DA functioning including motoric ability, DA release, and D2 receptor densities for 1 to 3 months post drug administration. Interestingly, DA content was reduced 1 week after 3-NP exposure, but rose to 147% of control values 1 month after 3-NP treatment. MDA accumulation, a measure of lipid peroxidation activity, was increased 24 hr and 1 month after 3-NP treatment. 3-NP did not affect tyrosine hydroxylase activity, suggesting that alterations in DA functioning were not the result of nigrostriatal terminal loss. These data demonstrate that a brief mild hypoxic episode caused by 3-NP exposure has long-term detrimental effects on the functioning of the nigrostriatal DA system. PMID:20730800

  4. SOC REJECTION BY NANOFILTRATION

    EPA Science Inventory

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

  5. "Science" Rejects Postmodernism.

    ERIC Educational Resources Information Center

    St. Pierre, Elizabeth Adams

    2002-01-01

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

  6. Successful multiple-step management of intravenous leiomyomatosis diagnosed after episode of acute abdominal pain: Case report and review of literature

    PubMed Central

    Efthimiadis, Christoforos; Petousis, Stamatios; Grigoriou, Marios; Ioannidis, Aristeidis; Tzouveleki, Ioanna; Margioula-Siarkou, Chrysoula; Kalogiannidis, Ioannis

    2015-01-01

    Introduction We present the case of a 37-year old woman diagnosed with intravenous leiomyomatosis (IVL) that was managed uneventfully with multiple-step management. Presentation of case A 37-year-old woman was admitted because of acute abdominal pain. Emergency Computed Tomography demonstrated a big pelvic mass 5 × 15 cm of heterogenous composition intaking the contrast agent. Total hysterectomy with salpingoophorectomy was proposed to patient, however, patient expressed her will for fertility preservation and gave consent only for the resection of a single ovary. Laparotomy revealed the presence of myoma, multiple lesions of potential adenomyosis and cordon-shaped formations arising from uterus and extending mainly to left ovary. Final histological diagnosis was intravenous leiomyomatosis (IVL). MRI angiography revealed the presence of residual lesions in inferior vena cava. Laparoscopic resection was performed one month after laparotomy and left ovary was resected without complications. Venovenous bypass was finally performed three months later from initial surgery. The process was significantly labored, resulted in the successful resection of intravenous lesions but was complicated intraoperatively by right kidney rupture. After a follow-up of 33 months, case remains uncomplicated without signs or symptoms of potential recurrence. Discussion Intravenous leiomyomatosis represents a rare clinical entity histologically bening but clinically aggressive. No consensus exists regarding the optimal management, especially in cases with initial will for fertility preservation. Conclusion IVL represents a rare clinical entity often presenting difficulties in diagnosis and optimal treatment. Large case-series studies should be encouraged to assess the optimal management. PMID:26282558

  7. Codominant Role of Interferon-γ– and Interleukin-17–Producing T Cells During Rejection in Full Facial Transplant Recipients

    PubMed Central

    Borges, T. J.; O’Malley, J. T.; Wo, L.; Murakami, N.; Smith, B.; Azzi, J.; Tripathi, S.; Lane, J. D.; Bueno, E. M.; Clark, R. A.; Tullius, S. G.; Chandraker, A.; Lian, C. G.; Murphy, G. F.; Strom, T. B.; Pomahac, B.; Najafian, N.; Riella, L. V.

    2016-01-01

    Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean followup of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-c/interleukin-17–producing cells in peripheral blood and in the allograft’s skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17–mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development. PMID:26749226

  8. Soothing the Sting of Rejection.

    ERIC Educational Resources Information Center

    Campbell, Joan Daniels

    1990-01-01

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

  9. Eculizumab for Treatment of Refractory Antibody-Mediated Rejection in Kidney Transplant Patients: A Single-Center Experience.

    PubMed

    Yelken, B; Arpalı, E; Görcin, S; Kocak, B; Karatas, C; Demiralp, E; Turkmen, A

    2015-01-01

    Antibody-mediated rejection (AMR) is responsible for up to 20%-30% of acute rejection episodes after kidney transplantation. In several cases, conventional therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD20 therapy can resolve AMR successfully. But in some cases the load of immunoglobulins that can activate complement cascade may submerge the routine desensitization therapy and result in the formation of membrane attack complexes. Eculizumab, a monoclonal antibody against C5, was reported to be an option in cases with severe AMR that are resistant to conventional therapy. Here, we present 8 cases that were resistant to conventional therapy and in which eculizumab was given as a salvage treatment. Given the bad prognosis for renal transplants displaying acute injury progressing rapidly to cortical necrosis on the biopsy, the prompt use of eculizumab could have the advantage of immediate effects by stopping cellular injury. This can provide a therapeutic window to allow conventional treatment modalities to be effective and prevent early graft loss. PMID:26293046

  10. Talking about Teaching Episodes

    ERIC Educational Resources Information Center

    Nemirovsky, Ricardo; DiMattia, Cara; Ribeiro, Branca; Lara-Meloy, Teresa

    2005-01-01

    This paper examines two types of discourse in which teachers engage when discussing case studies based on classroom episodes, and the ways in which the availability of video data of these episodes may motivate a shift in the mode of discourse used. We interviewed two pairs of secondary school mathematics teachers after they had read a case study…

  11. Heat rejection system

    DOEpatents

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

    1980-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  13. Autophagy in allografts rejection: A new direction?

    PubMed

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

    2016-03-18

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

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

    PubMed Central

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

    2015-01-01

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

  15. Accepters and Rejecters of Counseling.

    ERIC Educational Resources Information Center

    Rose, Harriett A.; Elton, Charles F.

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

  16. Transplant rejection and paradigms lost

    PubMed Central

    Strom, Terry B.

    2013-01-01

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

  17. Episodic coronal heating

    NASA Astrophysics Data System (ADS)

    Sturrock, P. A.; Dixon, W. W.; Klimchuk, J. A.; Antiochos, S. K.

    1990-06-01

    A study is made of the observational consequences of the hypothesis that there is no steady coronal heating, the solar corona instead being heated episodically, such that each short burst of heating is followed by a long period of radiative cooling. The form of the resulting contribution to the differential emission measure (DEM), and to a convenient related function (the differential energy flux, DEF) is calculated. Observational data for the quiet solar atmosphere indicate that the upper branch of the DEM, corresponding to temperatures above 100,000 K, can be interpreted in terms of episodic energy injection at coronal temperatures.

  18. Episodic coronal heating

    NASA Technical Reports Server (NTRS)

    Sturrock, P. A.; Dixon, W. W.; Klimchuk, J. A.; Antiochos, S. K.

    1990-01-01

    A study is made of the observational consequences of the hypothesis that there is no steady coronal heating, the solar corona instead being heated episodically, such that each short burst of heating is followed by a long period of radiative cooling. The form of the resulting contribution to the differential emission measure (DEM), and to a convenient related function (the differential energy flux, DEF) is calculated. Observational data for the quiet solar atmosphere indicate that the upper branch of the DEM, corresponding to temperatures above 100,000 K, can be interpreted in terms of episodic energy injection at coronal temperatures.

  19. Monitoring of corneal allograft rejection using laser flare meter

    NASA Astrophysics Data System (ADS)

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

    1998-10-01

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

  20. Prevention trumps treatment of antibody-mediated transplant rejection

    PubMed Central

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

    2010-01-01

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

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

    SciTech Connect

    Eisenberg, S.B.; Eisen, H.J.; Sobel, B.E.; Bergmann, S.R.; Bolman, R.M. 3d.

    1988-12-01

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

  3. Episodes, events, and models.

    PubMed

    Khemlani, Sangeet S; Harrison, Anthony M; Trafton, J Gregory

    2015-01-01

    We describe a novel computational theory of how individuals segment perceptual information into representations of events. The theory is inspired by recent findings in the cognitive science and cognitive neuroscience of event segmentation. In line with recent theories, it holds that online event segmentation is automatic, and that event segmentation yields mental simulations of events. But it posits two novel principles as well: first, discrete episodic markers track perceptual and conceptual changes, and can be retrieved to construct event models. Second, the process of retrieving and reconstructing those episodic markers is constrained and prioritized. We describe a computational implementation of the theory, as well as a robotic extension of the theory that demonstrates the processes of online event segmentation and event model construction. The theory is the first unified computational account of event segmentation and temporal inference. We conclude by demonstrating now neuroimaging data can constrain and inspire the construction of process-level theories of human reasoning. PMID:26578934

  4. Episodes, events, and models

    PubMed Central

    Khemlani, Sangeet S.; Harrison, Anthony M.; Trafton, J. Gregory

    2015-01-01

    We describe a novel computational theory of how individuals segment perceptual information into representations of events. The theory is inspired by recent findings in the cognitive science and cognitive neuroscience of event segmentation. In line with recent theories, it holds that online event segmentation is automatic, and that event segmentation yields mental simulations of events. But it posits two novel principles as well: first, discrete episodic markers track perceptual and conceptual changes, and can be retrieved to construct event models. Second, the process of retrieving and reconstructing those episodic markers is constrained and prioritized. We describe a computational implementation of the theory, as well as a robotic extension of the theory that demonstrates the processes of online event segmentation and event model construction. The theory is the first unified computational account of event segmentation and temporal inference. We conclude by demonstrating now neuroimaging data can constrain and inspire the construction of process-level theories of human reasoning. PMID:26578934

  5. Space vehicle thermal rejection system

    NASA Technical Reports Server (NTRS)

    Tanzer, Herbert J. (Inventor)

    1989-01-01

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

  6. The Role of Episodic and Semantic Memory in Episodic Foresight

    ERIC Educational Resources Information Center

    Martin-Ordas, Gema; Atance, Cristina M.; Louw, Alyssa

    2012-01-01

    In this paper we describe a special form of future thinking, termed "episodic foresight" and its relation with episodic and semantic memory. We outline the methodologies that have largely been developed in the last five years to assess this capacity in young children and non-human animals. Drawing on Tulving's definition of episodic and semantic…

  7. Perspectives on Episodic-Like and Episodic Memory

    PubMed Central

    Pause, Bettina M.; Zlomuzica, Armin; Kinugawa, Kiyoka; Mariani, Jean; Pietrowsky, Reinhard; Dere, Ekrem

    2013-01-01

    Episodic memory refers to the conscious recollection of a personal experience that contains information on what has happened and also where and when it happened. Recollection from episodic memory also implies a kind of first-person subjectivity that has been termed autonoetic consciousness. Episodic memory is extremely sensitive to cerebral aging and neurodegenerative diseases. In Alzheimer’s disease deficits in episodic memory function are among the first cognitive symptoms observed. Furthermore, impaired episodic memory function is also observed in a variety of other neuropsychiatric diseases including dissociative disorders, schizophrenia, and Parkinson disease. Unfortunately, it is quite difficult to induce and measure episodic memories in the laboratory and it is even more difficult to measure it in clinical populations. Presently, the tests used to assess episodic memory function do not comply with even down-sized definitions of episodic-like memory as a memory for what happened, where, and when. They also require sophisticated verbal competences and are difficult to apply to patient populations. In this review, we will summarize the progress made in defining behavioral criteria of episodic-like memory in animals (and humans) as well as the perspectives in developing novel tests of human episodic memory which can also account for phenomenological aspects of episodic memory such as autonoetic awareness. We will also define basic behavioral, procedural, and phenomenological criteria which might be helpful for the development of a valid and reliable clinical test of human episodic memory. PMID:23616754

  8. 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.

  9. Genetics Home Reference: episodic ataxia

    MedlinePlus

    ... Ebers GC. A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia. Neurology. ... investigators. Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain. 2007 Oct;130(Pt 10):2484-93. Epub ...

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-03-24

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

  12. Universal noninvasive detection of solid organ transplant rejection

    PubMed Central

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

    2011-01-01

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

  13. The Composition of Episodic Memory.

    ERIC Educational Resources Information Center

    Underwood, Benton J.; And Others

    This study examined the interrelationships among a number of episodic memory tasks and among various attributes of memory. A sample of 200 college students was tested for ten sessions; 28 different measures of episodic memory were obtained. In addition, five measures of semantic memory were available. Results indicated that episodic and semantic…

  14. Attentional Episodes in Visual Perception

    ERIC Educational Resources Information Center

    Wyble, Brad; Potter, Mary C.; Bowman, Howard; Nieuwenstein, Mark

    2011-01-01

    Is one's temporal perception of the world truly as seamless as it appears? This article presents a computationally motivated theory suggesting that visual attention samples information from temporal episodes (episodic simultaneous type/serial token model; Wyble, Bowman, & Nieuwenstein, 2009). Breaks between these episodes are punctuated by periods…

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

    PubMed Central

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

    2016-01-01

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

  16. Recurrent Episodes of Dissociative Fugue

    PubMed Central

    Angothu, Hareesh; Pabbathi, Lokeswar Reddy

    2016-01-01

    Dissociative fugue is rare entity to encounter with possible differentials of epilepsy and malingering. It is one of the dissociative disorders rarely seen in clinical practice more often because of the short lasting nature of this condition. This might also be because of organized travel of the individuals during the episodes and return to their families after the recovery from episodes. This is a case description of a patient who has experienced total three episodes of dissociative fugue. The patient has presented during the third episode and two prior episodes were diagnosed as fugue episodes retrospectively based on the history. Planned travel in this case by the patient to a distant location was prevented because of early diagnosis and constant vigilance till the recovery. As in this case, it may be more likely that persons with Dissociative fugue may develop similar episodes if they encounter exceptional perceived stress. However, such conclusions may require follow-up studies. PMID:27114633

  17. 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

  18. Treatment of Antibody-Mediated Rejection After Kidney Transplantation - 10 Years' Experience With Apheresis at a Single Center.

    PubMed

    Gubensek, Jakob; Buturovic-Ponikvar, Jadranka; Kandus, Aljosa; Arnol, Miha; Lindic, Jelka; Kovac, Damjan; Rigler, Andreja Ales; Romozi, Karmen; Ponikvar, Rafael

    2016-06-01

    Antibody-mediated rejection (AMR) is a major cause of kidney graft failure. We aimed to analyze treatment and outcome of AMR in a national cohort of 75 biopsy-proven acute (43 patients, 57%) or chronic active (32 patients, 43%) AMR episodes between 2000 and 2015. The mean patients' age was 46 ± 16 years, the majority was treated with plasma exchange, 4% received immunoadsorption and 7% received both. The majority received pulse methylprednisolone and low-dose CMV hyperimmune globulin, 20% received bortezomib and 13% rituximab. Concomitant infection was treated in 40% of patients. The immediate treatment outcome was successful in 91%, the 1- and 3-year graft survival rates were 71% and 57%, while 3-year patient survival was 97%. Chronic active AMR was associated with worse graft survival than acute AMR (log rank P = 0.06). To conclude, intensive treatment with apheresis and additional immunosuppression was effective in reversing AMR, but long-term graft survival remains markedly decreased, especially in chronic active AMR. PMID:27312908

  19. Perturbations in the Urinary Exosome in Transplant Rejection

    SciTech Connect

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

    2015-01-05

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

  20. Episodicity of Orogeny Revisited

    NASA Astrophysics Data System (ADS)

    Condie, K. C.; Aster, R. C.

    2008-12-01

    Although it is well established that orogeny is episodic, the duration, correlation and geographic distribution of orogenic episodes is not well constrained. Using large numbers of concordant U/Pb zircon ages from subduction-related granitoids (> 7000), it is now possible to better constrain these variables. Monte Carlo simulation probabilistic histograms of zircon age spectra remove questionable and spurious age peaks, yet allow resolution of peaks with >10 My duration with the data sets. Orogenic episodes with durations < 20 My, herein called pulses, are generally of regional geographic extent, whereas long-lived events (100-250 My), herein called periods, may be of regional or global extent. Orogenic periods comprise several to many pulses. Most orogenic pulses reflect geographic variations in intensity of subduction or/and plate collisions as for instance recorded around the perimeter of the Pacific basin in the last 100 My. Neither of the widely recognized pulses at 2.7 nor 1.9 Ga is global in extent. Orogenic pulses at 2700 and 2680 Ma occur on four continents each (2700: Superior, Hearne-Rae, Nain, North China; 2680: Yilgarn, Africa, Slave, Wyoming). Likewise, an orogenic pulse at 1880 is found on four continents (Laurentia, Baltica, East Asia, South America), and another pulse at 1860 Ma occurs on three continents (Africa, Siberia, Australia). Some orogenic pulses track lateral continental growth, such as 2730, 2715, and 2700 Ma pulses in the Abitibi greenstone belt, and 850, 800 and 750 Ma pulses in the Arabian-Nubian shield. Major orogenic periods are recognized at 2750-2650, 1900-1650, and 1250-1000 Ma and each of these is associated with supercontinent formation. Orogenic periods at 2600-2500 (China and India) and 2150-2050 Ma (West Africa, Amazonia, Rio de la Plata) may be associated with the formation of small supercontinents. Our results suggest that orogenic periods with intervening gaps may not require sudden and short-lived changes in mantle

  1. Infection related renal impairment: a major cause of acute allograft dysfunction.

    PubMed

    Nampoory, Mangalathillam R N; Johny, Kaivilayil V; Costandy, Jamal N; Nair, Madhavan P; Said, Tarek; Homoud, Hani; Al-Muzairai, Ibrahim; Samhan, Mohmoud; Al-Moussawi, Mustafa

    2003-06-01

    We prospectively analyzed the impact of post-transplant infections on the renal function in 532 stable renal transplant recipients (M=340; F=192) over a period of 5 years. Their age ranged from 3-75 years (40+14 years). During the follow-up period, 52 patients expired and 64 lost on followup. We defined renal impairment (RI) as a persistent rise in serum creatinine above 20% from baseline value. 495 episodes of RI occurred in 269 recipients. This included 180-36% episodes of acute rejection, 53-10.7% Cyclosporine toxicity, 236-47.7% infection related renal impairment [IRRI] and 26-5.3% others. The severity of renal failure is less in IRRI (100+90.2) than that of acute rejection (166+127.1), but was more than that in cyclosporine toxicity (50+42.2). Sites of infection in IRRI were urinary (33%), respiratory (26.3%), septicemia (15.7%) and others (25.4%). Episode of IRRI occurred more frequently in LURD (159-67.4%) compared to LRD-RTR (50-21.2%). Occurrence of IRRI is more significantly higher in patients on triple drug immunosuppression (IS) (34.3%) than those on two drug IS (13.2%) (P=or<0.01). Ecoli (23.1%), Pseudomonas (11.1%), Salmonella (8.8%), Klebsiella (8.8%) and Staphylococai (8.3%) were the major organisms producing IRRI. IRRI is frequent (27.8%) during the first six months. Present study denotes that IRRI is a major cause of acute failure in RTR. PMID:15859909

  2. Episodic Tremor at UPSAR

    NASA Astrophysics Data System (ADS)

    Fletcher, J. B.; Spudich, P.; Baker, L. M.

    2008-12-01

    UPSAR (U.S. Geological Survey Parkfield Seismic Array) was modified to record continuously at 40 sps in January 2005 following reports that tremor near Cholame had been detected. During January and early February, numerous episodes of tremor were recorded including one on January 21 at 07.58 UTC, which was recorded with particularly high signal levels. Here we report on the azimuth and apparent velocity of the waves from tremor impinging on the array and what these array measurements suggest about the location, depth, and frequency of tremor on the Parkfield/Cholame segment of the San Andreas fault. 11 stations were used in the analysis. We used cross correlation of all pairs of stations to determine slowness of incoming rays to analyze tremor data. A number of checks were made on the method such as correctly locating micro- earthquakes on the San Andreas fault. The tremor sources were localized to a section of the San Andreas fault south of where Highway 46 crosses the Cholame valley close to previous estimates of tremor locations. Depths are in the 14-24km range, below the seismogenic zone, but above the Moho. Estimates of error do not preclude locations below the Moho, however. Apparent velocity diminish by 0.5 to 1 km/s as the tremor episode progresses for about 3/4 of the total duration, implying a change in depth of the source, but the effect is small and may not be statistically significant. Polarizations across the array appear to be affected by local topography and show significant scatter. Nonetheless a NE-SW trend is apparent at some stations. Polarizations of direct S-waves from an earthquake near Cholame are more consistent and again trend NE- SW. Early coda from the same earthquake display polarization patterns similar to that for tremor suggesting that tremor signals are scattered rather than direct S waves.

  3. Moral judgment in episodic amnesia.

    PubMed

    Craver, Carl F; Keven, Nazim; Kwan, Donna; Kurczek, Jake; Duff, Melissa C; Rosenbaum, R Shayna

    2016-08-01

    To investigate the role of episodic thought about the past and future in moral judgment, we administered a well-established moral judgment battery to individuals with hippocampal damage and deficits in episodic thought (insert Greene et al. 2001). Healthy controls select deontological answers in high-conflict moral scenarios more frequently when they vividly imagine themselves in the scenarios than when they imagine scenarios abstractly, at some personal remove. If this bias is mediated by episodic thought, individuals with deficits in episodic thought should not exhibit this effect. We report that individuals with deficits in episodic memory and future thought make moral judgments and exhibit the biasing effect of vivid, personal imaginings on moral judgment. These results strongly suggest that the biasing effect of vivid personal imagining on moral judgment is not due to episodic thought about the past and future. © 2016 Wiley Periodicals, Inc. PMID:27028169

  4. Augmented orbiter heat rejection study

    NASA Technical Reports Server (NTRS)

    Hixon, C. W.

    1981-01-01

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

  5. The evolution of episodic memory

    PubMed Central

    Allen, Timothy A.; Fortin, Norbert J.

    2013-01-01

    One prominent view holds that episodic memory emerged recently in humans and lacks a “(neo)Darwinian evolution” [Tulving E (2002) Annu Rev Psychol 53:1–25]. Here, we review evidence supporting the alternative perspective that episodic memory has a long evolutionary history. We show that fundamental features of episodic memory capacity are present in mammals and birds and that the major brain regions responsible for episodic memory in humans have anatomical and functional homologs in other species. We propose that episodic memory capacity depends on a fundamental neural circuit that is similar across mammalian and avian species, suggesting that protoepisodic memory systems exist across amniotes and, possibly, all vertebrates. The implication is that episodic memory in diverse species may primarily be due to a shared underlying neural ancestry, rather than the result of evolutionary convergence. We also discuss potential advantages that episodic memory may offer, as well as species-specific divergences that have developed on top of the fundamental episodic memory architecture. We conclude by identifying possible time points for the emergence of episodic memory in evolution, to help guide further research in this area. PMID:23754432

  6. The Episodic Nature of Episodic-Like Memories

    ERIC Educational Resources Information Center

    Easton, Alexander; Webster, Lisa A. D.; Eacott, Madeline J.

    2012-01-01

    Studying episodic memory in nonhuman animals has proved difficult because definitions in humans require conscious recollection. Here, we assessed humans' experience of episodic-like recognition memory tasks that have been used with animals. It was found that tasks using contextual information to discriminate events could only be accurately…

  7. High frequency of IL-4 producing helper T lymphocytes associated with a reduced incidence of heart allograft rejection.

    PubMed

    Van Hoffen, E; Polen, E; Robertus-Teunissen, M; De Jonge, N; Lahpor, J R; Gmelig-Meyling, F H; De Weger, R A

    2000-01-01

    The reduction in the frequency of rejection episodes several months after heart transplantation (HTX) correlates with the development of donor-specific nonresponsiveness. This is reflected in a reduced frequency of donor-specific cytotoxic T cells (CTL) in the peripheral blood. We investigated whether the reduced CTL frequency and the incidence of rejection episodes coincided with a change in the frequency of either IL-2- or IL-4-producing helper T lymphocytes (HTL). We measured the frequency of HTL before and at several time points after HTX in the blood of ten recipients, using limiting dilution analysis for IL-2 and IL-4. In most patients, HTL frequencies dropped immediately after transplantation, but returned to pre-HTX values later after transplantation. No consistent decrease or increase in frequencies was observed long after HTX. In contrast to IL-2, the HTL frequencies for IL-4 before transplantation were significantly higher in patients without post-HTX rejection episodes requiring treatment than in patients with such episodes. This phenomenon was observed for the in vitro responses towards both donor and third-party cells. In conclusion, relatively high frequencies of IL-4-producing T cells may have a beneficial effect on the outcome of human heart transplantation, because they are associated with a reduced incidence of rejection episodes after transplantation. PMID:11111999

  8. Rejection of the second allogeneic graft in a child with Fanconi anemia reversed by antilymphocyte globulin and donor lymphocyte infusion.

    PubMed

    Abdelkefi, Abderrahman; Ben Othman, T; Ladeb, S; Torjman, L; Ben Abdeladhim, A

    2003-01-01

    Rejection after allogeneic bone marrow transplantation for Fanconi anemia (FA) is a complication with a high risk of mortality. We describe a patient who, following a second episode of rejection after a second allogeneic stem cell transplantation, was successfully treated with antilymphocyte globulin, followed by donor lymphocyte infusion. At three and a half years after donor lymphocyte infusion, she is alive with a Karnofsky score of 90%. Her molecular chimerism is of donor origin. Thus, donor lymphocyte infusion can be considered as a therapy option for rejection after allogeneic bone marrow transplantation for FA. PMID:14671621

  9. 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

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

    PubMed

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

    2016-01-01

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

  11. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  12. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  13. 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...

  14. 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...

  15. 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…

  16. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

  17. 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

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

    PubMed

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

    2016-05-01

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

  19. The Effect of ABO Blood Incompatibility on Corneal Transplant Failure in Conditions with Low Risk of Graft Rejection

    PubMed Central

    Dunn, Steven P.; Stark, Walter J.; Doyle Stulting, R.; Lass, Jonathan H.; Sugar, Alan; Pavilack, Mark A.; Smith, Patricia W.; Tanner, Jean Paul; Dontchev, Mariya; Gal, Robin L.; Beck, Roy W.; Kollman, Craig; Mannis, Mark J.; Holland, Edward J.

    2009-01-01

    Purpose To determine whether corneal graft survival over a five-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs’ dystrophy or pseudophakic corneal edema, conditions at low risk for graft rejection. Design Multi-center prospective, double-masked, clinical trial Methods ABO blood group compatibility was determined for 1,002 donors and recipients. During a five-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were due to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects. Results ABO donor-recipient incompatibility was not associated with graft failure due to any cause including graft failure due to rejection, or with the occurrence of a rejection episode. The five-year cumulative incidence of graft failure due to rejection was 6% for recipients with ABO recipient-donor compatibility and 4% for those with ABO incompatibility (hazard ratio 0.65, 95% confidence interval 0.33 to 1.25, p=0.20). The five-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 12% for ABO compatible compared with 8% for ABO incompatible cases (p=0.09). Among clear grafts at five years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases. Conclusions In patients undergoing penetrating keratoplasty for Fuchs’ dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure due to graft rejection. PMID:19056078

  20. Stroke-like episodes in familial mitochondrial encephalomyopathy: clinical and biochemical aspects.

    PubMed

    Damian, M S; Reichmann, H; Schütz, H J; Dorndorf, W; Schachenmayr, W

    1991-04-01

    Acute episodes of focal neurological dysfunction are a well-recognized complication of the mitochondrial encephalomyopathies. Because of rapid remission, biochemical tests and other diagnostic procedures are mostly performed after the acute phase. We report the case of a patient suffering from mitochondrial disease manifesting primarily with seizures, progressive deafness and dementia, who experienced multiple stroke-like episodes. Other members of the family with evidence of mitochondrial dysfunction are presented briefly. EEG and biochemical findings in the acute stage are correlated with clinical symptoms, showing characteristics distinct from the chronic illness. The possible involvement of dietary factors in the provocation of stroke-like episodes is discussed and regulation of glucose intake suggested as a strategy in the prevention of stroke-like episodes. PMID:1906933

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

    PubMed Central

    2012-01-01

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

  2. Behind the Webb Episode 27

    NASA Video Gallery

    This episode of "Behind the Webb" explores the multi-tasking capabilities of one of the cameras on the Webb Space Telescope, the Near-Infrared Spectrograph. Newly designed technology known as "micr...

  3. Saharan dust episodes and pregnancy.

    PubMed

    Dadvand, Payam; Basagaña, Xavier; Figueras, Francesc; Amoly, Elmira; Tobias, Aurelio; de Nazelle, Audrey; Querol, Xavier; Sunyer, Jordi; Nieuwenhuijsen, Mark J

    2011-11-01

    Desert dust is one of the natural contributors to atmospheric particulate matter worldwide. Although particulate pollution has been shown to adversely affect pregnancy, the available evidence on the impact of dust episodes on pregnancy is very scarce. The aim of this study was to evaluate the impact of Saharan dust episodes on pregnancy complications (preeclampsia and bacteriuria) and outcomes (birth weight and gestational age at delivery). This study was based on a cohort of births (N = 3565) that occurred in a major university hospital in Barcelona during 2003-2005. To determine Saharan dust episodes, we developed a two-stage approach based on meteorological evidence of the presence of Saharan dust cloud over the region and unusually high levels of particulate levels on the ground while taking account of traffic sources. The associations between the number of Saharan dust episodes during whole pregnancy as well as each pregnancy trimester and pregnancy complications and outcomes were analysed. There were 152 days (out of 838 days) with Saharan dust cloud over the region from which 45 days were determined as episodic days. We did not observe any statistically significant harmful effect of Saharan dust episodes on our included pregnancy complications and outcomes. However, we observed a small but statistically significant increase in gestational age at delivery in association with the number of episodic days during the third trimester and whole pregnancy (0.8 and 0.5 days respectively). Our findings were not suggestive for any adverse effect of Saharan dust episodes on our included pregnancy complications and outcomes. PMID:21964628

  4. Monocyte procoagulant activity and plasminogen activator. Role in human renal allograft rejection

    SciTech Connect

    Cole, E.H.; Cardella, C.J.; Schulman, J.; Levy, G.A.

    1985-10-01

    Currently the mechanism of renal allograft rejection is not well understood. This study was designed to determine whether induction of monocyte procoagulant activity (MCPA) is important in the pathogenesis of renal allograft rejection. The MPCA assay was performed utilizing a one stage clotting assay both in normal and in factor-VII-deficient plasma. There was no increase in spontaneous MPCA in 20 patients with endstage renal failure and in 10 patients following abdominal or orthopedic operation, as compared with 20 normal controls. MPCA was assessed daily in 18 patients who had received renal allografts. Rejection episodes (RE) were predicted on the basis of persistent elevation in MPCA as compared with pretransplant levels. Rejection was diagnosed clinically and treated on the basis of standard criteria. Treated RE were compared with those predicted by elevated MPCA, and 3 patients were assessed as having no RE by MPCA and by standard criteria. In 8 RE, MPCA correlated temporally with RE (same day) when compared with standard criteria. In 12 RE, MPCA was predictive of rejection preceding standard criteria by at least 24 hr. There were 7 false-positive predictions on the basis of MPCA; however, there was only 1 false negative. MPCA was shown to be a prothrombinase by its dependence only on prothrombin and fibrinogen for full activity. MPCA may be important in the pathogenesis of allograft rejection, and additionally it may be a useful adjunct in the clinical management of this disease.

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

    SciTech Connect

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

    1987-03-01

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

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

    PubMed

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

    2005-07-01

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

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

    PubMed

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

    2013-12-01

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

  8. Feigning Acute Intermittent Porphyria

    PubMed Central

    Elkhatib, Rania; Idowu, Modupe; Brown, Gregory S.; Jaber, Yasmeen M.; Reid, Matthew B.; Person, Cheryl

    2014-01-01

    Acute intermittent porphyria (AIP) is an autosomal dominant genetic defect in heme synthesis. Patients with this illness can have episodic life-threatening attacks characterized by abdominal pain, neurological deficits, and psychiatric symptoms. Feigning this illness has not been reported in the English language literature to date. Here, we report on a patient who presented to the hospital with an acute attack of porphyria requesting opiates. Diligent assessment of extensive prior treatment records revealed thirteen negative tests for AIP. PMID:25525547

  9. The effect of post-discharge educational intervention on patients in achieving objectives in modifiable risk factors six months after discharge following an episode of acute coronary syndrome, (CAM-2 Project): a randomized controlled trial

    PubMed Central

    2010-01-01

    Objectives We investigated whether an intervention mainly consisting of a signed agreement between patient and physician on the objectives to be reached, improves reaching these secondary prevention objectives in modifiable cardiovascular risk factors six-months after discharge following an acute coronary syndrome. Background There is room to improve mid-term adherence to clinical guidelines' recommendations in coronary heart disease secondary prevention, specially non-pharmacological ones, often neglected. Methods In CAM-2, patients discharged after an acute coronary syndrome were randomly assigned to the intervention or the usual care group. The primary outcome was reaching therapeutic objectives in various secondary prevention variables: smoking, obesity, blood lipids, blood pressure control, exercise and taking of medication. Results 1757 patients were recruited in 64 hospitals and 1510 (762 in the intervention and 748 in the control group) attended the six-months follow-up visit. After adjustment for potentially important variables, there were, between the intervention and control group, differences in the mean reduction of body mass index (0.5 vs. 0.2; p < 0.001) and waist circumference (1.6 cm vs. 0.6 cm; p = 0.05), proportion of patients who exercise regularly and those with total cholesterol below 175 mg/dl (64.7% vs. 56.5%; p = 0.001). The reported intake of medications was high in both groups for all the drugs considered with no differences except for statins (98.1% vs. 95.9%; p = 0.029). Conclusions At least in the short term, lifestyle changes among coronary heart disease patients are achievable by intensifying the responsibility of the patient himself by means of a simple and feasible intervention. PMID:21092191

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

    SciTech Connect

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

    1988-07-01

    Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.

  11. Factitious psychogenic nonepileptic paroxysmal episodes.

    PubMed

    Romano, Alissa; Alqahtani, Saeed; Griffith, James; Koubeissi, Mohamad Z

    2014-01-01

    Mistaking psychogenic nonepileptic paroxysmal episodes (PNEPEs) for epileptic seizures (ES) is potentially dangerous, and certain features should alert physicians to a possible PNEPE diagnosis. Psychogenic nonepileptic paroxysmal episodes due to factitious seizures carry particularly high risks of morbidity or mortality from nonindicated emergency treatment and, often, high costs in wasted medical treatment expenditures. We report a case of a 28-year-old man with PNEPEs that were misdiagnosed as ES. The patient had been on four antiseizure medications (ASMs) with therapeutic serum levels and had had multiple intubations in the past for uncontrolled episodes. He had no episodes for two days of continuous video-EEG monitoring. He then disconnected his EEG cables and had an episode of generalized stiffening and cyanosis, followed by jerking and profuse bleeding from the mouth. The manifestations were unusually similar to those of ES, except that he was clearly startled by spraying water on his face, while he was stiff in all extremities and unresponsive. There were indications that he had sucked blood from his central venous catheter to expel through his mouth during his PNEPEs while consciously holding his breath. Normal video-EEG monitoring; the patient's volitional and deceptive acts to fabricate the appearance of illness, despite pain and personal endangerment; and the absence of reward other than remaining in a sick role were all consistent with a diagnosis of factitious disorder. PMID:25667902

  12. Factitious psychogenic nonepileptic paroxysmal episodes

    PubMed Central

    Romano, Alissa; Alqahtani, Saeed; Griffith, James; Koubeissi, Mohamad Z.

    2014-01-01

    Mistaking psychogenic nonepileptic paroxysmal episodes (PNEPEs) for epileptic seizures (ES) is potentially dangerous, and certain features should alert physicians to a possible PNEPE diagnosis. Psychogenic nonepileptic paroxysmal episodes due to factitious seizures carry particularly high risks of morbidity or mortality from nonindicated emergency treatment and, often, high costs in wasted medical treatment expenditures. We report a case of a 28-year-old man with PNEPEs that were misdiagnosed as ES. The patient had been on four antiseizure medications (ASMs) with therapeutic serum levels and had had multiple intubations in the past for uncontrolled episodes. He had no episodes for two days of continuous video-EEG monitoring. He then disconnected his EEG cables and had an episode of generalized stiffening and cyanosis, followed by jerking and profuse bleeding from the mouth. The manifestations were unusually similar to those of ES, except that he was clearly startled by spraying water on his face, while he was stiff in all extremities and unresponsive. There were indications that he had sucked blood from his central venous catheter to expel through his mouth during his PNEPEs while consciously holding his breath. Normal video-EEG monitoring; the patient's volitional and deceptive acts to fabricate the appearance of illness, despite pain and personal endangerment; and the absence of reward other than remaining in a sick role were all consistent with a diagnosis of factitious disorder. PMID:25667902

  13. Cingulum bundle diffusivity and delusions of reference in first episode and chronic schizophrenia

    PubMed Central

    Fitzsimmons, Jennifer; Schneiderman, Jason S.; Whitford, Thomas J.; Swisher, Tali; Niznikiewicz, Margaret A.; Pelavin, Paula E.; Terry, Douglas P.; Mesholam-Gately, Raquelle I.; Seidman, Larry J.; Goldstein, Jill M.; Kubicki, Marek

    2014-01-01

    The goal of this study was to assess integrity of the cingulum bundle in patients diagnosed with first episode schizophrenia, chronic schizophrenia, and matched controls as well as to determine the relationship between diffusion measures of cingulum bundle integrity and severity of patients’ delusions of reference. Participants, who comprised 18 first episode patients, 20 chronic patients, and two groups of matched controls (20 subjects in each), underwent 3 Tesla MRI diffusion tensor imaging. Patients diagnosed with schizophrenia (chronic + first episode) showed decreased fractional anisotropy in the right cingulum bundle compared with controls. First episode patients exhibited higher trace bilaterally, compared with matched controls, and on the left compared with chronic patients. Axial diffusivity was increased in first episode patients, bilaterally, compared with matched controls and chronic patients. Radial diffusivity was also higher, bilaterally, in first episode patients compared with matched controls, and on the right compared with chronic patients. Trace diffusity and radial diffusivity in first episode patients were significantly correlated with increased severity of delusions of reference. Given that the abnormalities were present only in first episode patients and were not observed in chronic cases, it appears that they normalize over time. These abnormalities in first episode patients involved diffusivity measures in all directions (trace, radial and axial), suggesting a likely acute, partially reversible process in which there is an increase in brain water content, i.e., swelling, edema, or inflammation, that may reflect an early neuroinflammatory response in first episode patients. PMID:25174840

  14. Cingulum bundle diffusivity and delusions of reference in first episode and chronic schizophrenia.

    PubMed

    Fitzsimmons, Jennifer; Schneiderman, Jason S; Whitford, Thomas J; Swisher, Tali; Niznikiewicz, Margaret A; Pelavin, Paula E; Terry, Douglas P; Mesholam-Gately, Raquelle I; Seidman, Larry J; Goldstein, Jill M; Kubicki, Marek

    2014-11-30

    The goal of this study was to assess integrity of the cingulum bundle in patients diagnosed with first episode schizophrenia, chronic schizophrenia, and matched controls as well as to determine the relationship between diffusion measures of cingulum bundle integrity and severity of patients' delusions of reference. Participants, who comprised 18 first episode patients, 20 chronic patients, and two groups of matched controls (20 subjects in each), underwent 3 T MRI diffusion tensor imaging. Patients diagnosed with schizophrenia (chronic+first episode) showed decreased fractional anisotropy in the right cingulum bundle compared with controls. First episode patients exhibited higher trace bilaterally, compared with matched controls, and on the left compared with chronic patients. Axial diffusivity was increased in first episode patients, bilaterally, compared with matched controls and chronic patients. Radial diffusivity was also higher, bilaterally, in first episode patients compared with matched controls, and on the right compared with chronic patients. Trace diffusity and radial diffusivity in first episode patients were significantly correlated with increased severity of delusions of reference. Given that the abnormalities were present only in first episode patients and were not observed in chronic cases, it appears that they normalize over time. These abnormalities in first episode patients involved diffusivity measures in all directions (trace, radial and axial), suggesting a likely acute, partially reversible process in which there is an increase in brain water content, i.e., swelling, edema, or inflammation, that may reflect an early neuroinflammatory response in first episode patients. PMID:25174840

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

    PubMed Central

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

    2016-01-01

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

  16. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

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

  17. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  18. Extended active disturbance rejection controller

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  19. Fractional active disturbance rejection control.

    PubMed

    Li, Dazi; Ding, Pan; Gao, Zhiqiang

    2016-05-01

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

  20. Episodic Memory: A Comparative Approach

    PubMed Central

    Martin-Ordas, Gema; Call, Josep

    2013-01-01

    Historically, episodic memory has been described as autonoetic, personally relevant, complex, context-rich, and allowing mental time travel. In contrast, semantic memory, which is theorized to be free of context and personal relevance, is noetic and consists of general knowledge of facts about the world. The field of comparative psychology has adopted this distinction in order to study episodic memory in non-human animals. Our aim in this article is not only to reflect on the concept of episodic memory and the experimental approaches used in comparative psychology to study this phenomenon, but also to provide a critical analysis of these paradigms. We conclude the article by providing new avenues for future research. PMID:23781179

  1. The impact of phenomena El Niño and La Niña and other environmental factors on episodes of acute diarrhoea disease in the population of Aguascalientes, Mexico: a case study

    NASA Astrophysics Data System (ADS)

    Esthela Venegas-Pérez, Martha; Ramírez-López, Elsa Marcela; López-Santos, Armando; Orlando Magaña-Rueda, Víctor; Avelar-González, Francisco Javier

    2016-03-01

    Acute diarrhoea diseases (ADDs) are one of the major health problems in Aguascalientes, Mexico. Due to the risk of significant increases of ADDs in the hot season, it has been necessary to determine the weather conditions that might lead to escalating ADD events. The effects of El Niño and La Niña phenomena on the morbidity rate of ADD (MRADD) in the State of Aguascalientes were determined during the period of 2000-2010. The MRADD was calculated from cases reported by the State Health Department. The Oceanic Niño Index (ONI) was obtained from the US National Oceanic and Atmospheric Administration. The impact of El Niño and La Niña on the MRADD was determined using the Pearson correlation coefficient and analysis of variance (ANOVA). The results gave a significant inverse correlation between El Niño phenomenon and MRADD (r = -0.55, P = 0.001), but a correlation was not observed on the La Niña phenomenon (r = -0.022, P = 0.888). Field data showed significant inverse influence of El Niño on MRADD for the years 2000-2010.

  2. Differentiating Acute Otitis Media and Acute Mastoiditis in Hospitalized Children.

    PubMed

    Laulajainen-Hongisto, Anu; Aarnisalo, Antti A; Jero, Jussi

    2016-10-01

    Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children. PMID:27613655

  3. Migration of objects and inferences across episodes.

    PubMed

    Hannigan, Sharon L; Reinitz, Mark Tippens

    2003-04-01

    Participants viewed episodes in the form of a series of photographs portraying ordinary routines (e.g., eating at a restaurant) and later received a recognition test. In Experiment 1, it was shown that objects (e.g., a vase of flowers, a pewter lantern) that appeared in a single episode during the study phase migrated between memories of episodes described by the same abstract schema (e.g., from Restaurant Episode A at study to Restaurant Episode B at test), and not between episodes anchored by different schemas. In Experiment 2, it was demonstrated that backward causal inferences from one study episode influenced memories of other episodes described by the same schema, and that high-schema-relevant items viewed in one episode were sometimes remembered as having occurred in another episode of the same schematic type. PMID:12795485

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

    PubMed Central

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

    2015-01-01

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

  5. 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...

  6. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  7. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  8. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  9. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  10. 47 CFR 61.69 - Rejection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  11. RAGG - R EPISODIC AGGREGATION PACKAGE

    EPA Science Inventory

    The RAGG package is an R implementation of the CMAQ episodic model aggregation method developed by Constella Group and the Environmental Protection Agency. RAGG is a tool to provide climatological seasonal and annual deposition of sulphur and nitrogen for multimedia management. ...

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

    Boucher, Anne; Collette, Suzon; Senécal, Lynne

    2016-01-01

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

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2016-04-01

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

  16. 43 CFR 3425.1-8 - Rejection of applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  17. 43 CFR 3430.5-1 - Rejection of application.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  18. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  19. 43 CFR 3430.5-1 - Rejection of application.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  20. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  2. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  3. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  4. 14 CFR 221.111 - Notification of rejection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  5. 43 CFR 3425.1-8 - Rejection of applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  6. 43 CFR 3430.5-1 - Rejection of application.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  7. 43 CFR 3425.1-8 - Rejection of applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  9. Long-lasting corneal endothelial graft rejection successfully reversed after dexamethasone intravitreal implant.

    PubMed

    Giannaccare, Giuseppe; Fresina, Michela; Pazzaglia, Alberto; Versura, Piera

    2016-01-01

    Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month follow-up visit, the clinical picture remains stable without any sign of rejection, recurrence, or graft failure. Dexamethasone intravitreal implant seems to be a new potential effective treatment for corneal graft rejection, particularly in case of poor compliance or lack of response to conventional

  10. Long-lasting corneal endothelial graft rejection successfully reversed after dexamethasone intravitreal implant

    PubMed Central

    Giannaccare, Giuseppe; Fresina, Michela; Pazzaglia, Alberto; Versura, Piera

    2016-01-01

    Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month follow-up visit, the clinical picture remains stable without any sign of rejection, recurrence, or graft failure. Dexamethasone intravitreal implant seems to be a new potential effective treatment for corneal graft rejection, particularly in case of poor compliance or lack of response to conventional

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

    PubMed Central

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

    2013-01-01

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

  12. Rejection of pharmaceuticals by forward osmosis membranes.

    PubMed

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

    2012-08-15

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

  13. The experimental study on heat rejection equipment

    NASA Astrophysics Data System (ADS)

    Nakagawa, Toshihiko; Atsumi, Masahiro; Tokue, Rinzo

    1992-07-01

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

  14. Pericytes, microvasular dysfunction and chronic rejection

    PubMed Central

    Kloc, Malgorzata; Kubiak, Jacek Z.; Li, Xian C.; Ghobrial, Rafik M.

    2014-01-01

    Chronic rejection of transplanted organs remains the main obstacle in the long-term success of organ transplantation. Thus, there is a persistent quest for development of anti-chronic rejection therapies and identification of novel molecular and cellular targets. One of the potential targets is the pericytes, the mural cells of microvessels, which regulate microvascular permeability, development and maturation by controlling endothelial cell functions and regulating tissue fibrosis and inflammatory response. In this review we discuss the potential of targeting pericytes in development of microvasular dysfunction and the molecular pathways involved in regulation of pericyte activities for anti-chronic rejection intervention. PMID:25793439

  15. Episodic Volunteers: Reality for the Future.

    ERIC Educational Resources Information Center

    Macduff, Nancy

    1990-01-01

    Episodic volunteer opportunities allow for short-term services--either one-time or recurring. The organization using such volunteers must identify new jobs that can be performed on an episodic basis or redesign traditional volunteer jobs. (SK)

  16. Enhanced B Cell Alloantigen Presentation and Its Epigenetic Dysregulation in Liver Transplant Rejection.

    PubMed

    Ningappa, M; Ashokkumar, C; Higgs, B W; Sun, Q; Jaffe, R; Mazariegos, G; Li, D; Weeks, D E; Subramaniam, S; Ferrell, R; Hakonarson, H; Sindhi, R

    2016-02-01

    T cell suppression prevents acute cellular rejection but causes life-threatening infections and malignancies. Previously, liver transplant (LTx) rejection in children was associated with the single-nucleotide polymorphism (SNP) rs9296068 upstream of the HLA-DOA gene. HLA-DOA inhibits B cell presentation of antigen, a potentially novel antirejection drug target. Using archived samples from 122 white pediatric LTx patients (including 77 described previously), we confirmed the association between rs9296068 and LTx rejection (p = 0.001, odds ratio [OR] 2.55). Next-generation sequencing revealed that the putative transcription factor (CCCTC binding factor [CTCF]) binding SNP locus rs2395304, in linkage disequilibrium with rs9296068 (D' 0.578, r(2) = 0.4), is also associated with LTx rejection (p = 0.008, OR 2.34). Furthermore, LTx rejection is associated with enhanced B cell presentation of donor antigen relative to HLA-nonidentical antigen in a novel cell-based assay and with a downregulated HLA-DOA gene in a subset of these children. In lymphoblastoid B (Raji) cells, rs2395304 coimmunoprecipitates with CTCF, and CTCF knockdown with morpholino antisense oligonucleotides enhances alloantigen presentation and downregulates the HLA-DOA gene, reproducing observations made with HLA-DOA knockdown and clinical rejection. Alloantigen presentation is suppressed by inhibitors of methylation and histone deacetylation, reproducing observations made during resolution of rejection. Enhanced donor antigen presentation by B cells and its epigenetic dysregulation via the HLA-DOA gene represent novel opportunities for surveillance and treatment of transplant rejection. PMID:26663361

  17. Extracorporeal photopheresis in heart transplant rejection.

    PubMed

    Patel, Jignesh; Klapper, Ellen; Shafi, Hedyeh; Kobashigawa, Jon A

    2015-04-01

    Up to 25% of heart transplant recipients develop rejection requiring intervention. While the majority respond to augmentation of immunomodulatory drug therapy, a subset of patients will remain refractory. Extracorporeal photopheresis (ECP) appears particularly useful in the management of select heart transplant recipients at risk of rejection, with recurrent rejection, or rejection associated with hemodynamic compromise. This chapter summarizes the current clinical experience of ECP in heart transplantation. ECP appears to favorably affect both the cellular and humoral arms of the immune response to the allograft and promote a tolerogenic profile. These immunomodulatory effects also appear to decrease development of cardiac allograft vasculopathy. ECP is generally well tolerated with few adverse effects and low infection risk. PMID:25748232

  18. Episodic pain in patients with advanced cancer.

    PubMed

    Zeppetella, Giovambattista; Ribeiro, Maria D C

    2002-01-01

    Episodic pain is a common problem for patients with advanced cancer and is often difficult to manage successfully. In this article, the daily variations in cancer-related episodic pain in a patient with metastatic lung cancer are described. The definition, etiology, prevalence, and pharmacological management of episodic pain are also reviewed PMID:12141792

  19. Planning Physical Education Lessons as Teaching "Episodes"

    ERIC Educational Resources Information Center

    Chatoupis, Constantine

    2016-01-01

    An "episode" is a unit of time within which teachers and students are working on the same objective and are engaged in the same teaching/learning style. The duration of each episode, as well as the number of them in a single lesson, may vary. Additionally, the multiple episodes of a lesson may have similar objectives, offer similar…

  20. DIPS organic rankine cycle heat rejection system

    SciTech Connect

    Pearson, R.

    1987-01-01

    The paper presents the results of an optimization study performed on the heat rejection system for a space based ORC power system using an isotope heat source. The radiator sizing depends on the heat rejection temperature, radiator configuration, and radiator properties such as the fin effectiveness, emissivity, and absorptivity. The optimization analysis to evaluate the effect of each of these parameters on the system weight and area is presented.

  1. Clutter rejection limitations from ambiguous range clutter

    NASA Astrophysics Data System (ADS)

    Reilly, J. Patrick

    Limitations on achievable clutter rejection due to ambiguous range clutter are described. The profile of clutter power versus range is shown to limit achievable clutter rejection. Ambiguous range effects are discussed in the context of sea clutter, using a model that includes propagation conditions, and rain clutter. Limitations in moving target indication systems are illustrated for sea clutter, where propagation is subject to evaporation ducts. Benefits of fill pulses are illustrated for rain and sea clutter.

  2. Episodic Memories in Anxiety Disorders: Clinical Implications

    PubMed Central

    Zlomuzica, Armin; Dere, Dorothea; Machulska, Alla; Adolph, Dirk; Dere, Ekrem; Margraf, Jürgen

    2014-01-01

    The aim of this review is to summarize research on the emerging role of episodic memories in the context of anxiety disorders (AD). The available literature on explicit, autobiographical, and episodic memory function in AD including neuroimaging studies is critically discussed. We describe the methodological diversity of episodic memory research in AD and discuss the need for novel tests to measure episodic memory in a clinical setting. We argue that alterations in episodic memory functions might contribute to the etiology of AD. We further explain why future research on the interplay between episodic memory function and emotional disorders as well as its neuroanatomical foundations offers the promise to increase the effectiveness of modern psychological treatments. We conclude that one major task is to develop methods and training programs that might help patients suffering from AD to better understand, interpret, and possibly actively use their episodic memories in a way that would support therapeutic interventions and counteract the occurrence of symptoms. PMID:24795583

  3. Image rejects in general direct digital radiography

    PubMed Central

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

    2015-01-01

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

  4. The fate of triaged and rejected manuscripts.

    PubMed

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

    2015-12-01

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

  5. Micro and nanoparticle drug delivery systems for preventing allotransplant rejection.

    PubMed

    Fisher, James D; Acharya, Abhinav P; Little, Steven R

    2015-09-01

    Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation. PMID:25937032

  6. Novel Multivariate Methods for Integration of Genomics and Proteomics Data: Applications in a Kidney Transplant Rejection Study

    PubMed Central

    Günther, Oliver P.; Shin, Heesun; Ng, Raymond T.; McMaster, W. Robert; McManus, Bruce M.; Keown, Paul A.; Tebbutt, Scott. J.

    2014-01-01

    Abstract Multi-omics research is a key ingredient of data-intensive life sciences research, permitting measurement of biological molecules at different functional levels in the same individual. For a complete picture at the biological systems level, appropriate statistical techniques must however be developed to integrate different ‘omics’ data sets (e.g., genomics and proteomics). We report here multivariate projection-based analyses approaches to genomics and proteomics data sets, using the case study of and applications to observations in kidney transplant patients who experienced an acute rejection event (n=20) versus non-rejecting controls (n=20). In this data sets, we show how these novel methodologies might serve as promising tools for dimension reduction and selection of relevant features for different analytical frameworks. Unsupervised analyses highlighted the importance of post transplant time-of-rejection, while supervised analyses identified gene and protein signatures that together predicted rejection status with little time effect. The selected genes are part of biological pathways that are representative of immune responses. Gene enrichment profiles revealed increases in innate immune responses and neutrophil activities and a depletion of T lymphocyte related processes in rejection samples as compared to controls. In all, this article offers candidate biomarkers for future detection and monitoring of acute kidney transplant rejection, as well as ways forward for methodological advances to better harness multi-omics data sets. PMID:25387159

  7. Cognitive Dissonance Resolution Is Related to Episodic Memory

    PubMed Central

    Maillet, Mathurin; Naccache, Lionel

    2014-01-01

    The notion that our past choices affect our future behavior is certainly one of the most influential concepts of social psychology since its first experimental report in the 50 s, and its initial theorization by Festinger within the “cognitive dissonance” framework. Using the free choice paradigm (FCP), it was shown that choosing between two similarly rated items made subjects reevaluate the chosen items as more attractive and the rejected items as less attractive. However, in 2010 a major work by Chen and Risen revealed a severe statistical flaw casting doubt on most previous studies. Izuma and colleagues (2010) supplemented the traditional FCP with original control conditions and concluded that the effect observed could not be solely attributed to this methodological flaw. In the present work we aimed at establishing the existence of genuine choice-induced preference change and characterizing this effect. To do so, we replicated Izuma et al.’ study and added a new important control condition which was absent from the original study. Moreover, we added a memory test in order to measure the possible relation between episodic memory of choices and observed behavioral effects. In two experiments we provide experimental evidence supporting genuine choice-induced preference change obtained with FCP. We also contribute to the understanding of the phenomenon by showing that choice-induced preference change effects are strongly correlated with episodic memory. PMID:25264950

  8. Cognitive dissonance resolution is related to episodic memory.

    PubMed

    Salti, Moti; El Karoui, Imen; Maillet, Mathurin; Naccache, Lionel

    2014-01-01

    The notion that our past choices affect our future behavior is certainly one of the most influential concepts of social psychology since its first experimental report in the 50 s, and its initial theorization by Festinger within the "cognitive dissonance" framework. Using the free choice paradigm (FCP), it was shown that choosing between two similarly rated items made subjects reevaluate the chosen items as more attractive and the rejected items as less attractive. However, in 2010 a major work by Chen and Risen revealed a severe statistical flaw casting doubt on most previous studies. Izuma and colleagues (2010) supplemented the traditional FCP with original control conditions and concluded that the effect observed could not be solely attributed to this methodological flaw. In the present work we aimed at establishing the existence of genuine choice-induced preference change and characterizing this effect. To do so, we replicated Izuma et al.' study and added a new important control condition which was absent from the original study. Moreover, we added a memory test in order to measure the possible relation between episodic memory of choices and observed behavioral effects. In two experiments we provide experimental evidence supporting genuine choice-induced preference change obtained with FCP. We also contribute to the understanding of the phenomenon by showing that choice-induced preference change effects are strongly correlated with episodic memory. PMID:25264950

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-08-01

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

  11. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  12. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  13. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  14. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  15. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  16. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  17. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  18. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  19. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  20. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  1. 28 CFR 540.13 - Notification of rejections.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Notification of rejections. 540.13... CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When correspondence is rejected, the Warden shall notify the sender in writing of the rejection and the reasons...

  2. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  3. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Rejection of application. 70.35 Section 70.35... Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by the... Department necessitate rejection of the application. (b) Each such applicant shall be promptly notified...

  4. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  5. 9 CFR 354.35 - Rejection of application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Rejection of application. 354.35... Inspection Service § 354.35 Rejection of application. Any application for inspection service may be rejected.... Each such applicant shall be promptly notified by registered mail of the reasons for the rejection....

  6. Belatacept prophylaxis against organ rejection in adult kidney-transplant recipients.

    PubMed

    Del Bello, Arnaud; Marion, Olivier; Milongo, David; Rostaing, Lionel; Kamar, Nassim

    2016-02-01

    End-stage renal disease is a major health problem worldwide, with kidney transplantation being the treatment of choice. Calcineurin inhibitors are still the cornerstone of immunosuppressive therapy. However, they have well-known nephrotoxic affects and increase the risk of cardiovascular disease and cancer. In contrast, belatacept is a biological immunosuppressive agent that inhibits the T-cell co-stimulation. It is approved by the US Food and Drug Administration and the European Medicine Agency for use in adult kidney-transplant recipients to prevent acute rejection. Developmental studies show that belatacept is as efficient as calcineurin inhibitors at preventing acute rejection. In addition, kidney function is better and cardiovascular risk factors are reduced in patients given belatacept. Herein, the authors review the published evidence concerning the efficacy and safety of belatacept and discuss its potential specific indications. PMID:26691282

  7. Rejection of pharmaceuticals by nanofiltration (NF) membranes: Effect of fouling on rejection behaviour

    NASA Astrophysics Data System (ADS)

    Mahlangu, T. O.; Msagati, T. A. M.; Hoek, E. M. V.; Verliefde, A. R. D.; Mamba, B. B.

    The aim of this study was to investigate the effects of membrane fouling by sodium alginate, latex and a combination of alginate + latex on the rejection behaviour of salts and organics. Sodium chloride and caffeine were selected to represent salts and organics, respectively. The effects of the presence of calcium chloride on the fouling behaviour and rejection of solutes were investigated. The results revealed that the salt rejection by virgin membranes was 47% while that of caffeine was 85%. Fouling by alginate, latex and combined alginate-latex resulted in flux decline of 25%, 37% and 17%, respectively. The addition of Ca2+ aggravated fouling and resulted in further flux decline to 37%. Fouling decreased salt rejection, an observation that was further aggravated by the addition on Ca2+. However, it was also observed that fouling with alginate and calcium and with latex and calcium minimised salt rejection by 30% and 31%, respectively. This reduction in salt rejection was attributed to the decrease in permeate flux (since rejection is a function of flux). There was a slight increase in caffeine rejection when the membrane was fouled with latex particles. Moreover, the presence of foulants on the membrane resulted in a decrease in the surface charge of the membrane. The results of this study have shown that the NF 270 membrane can be used to treat water samples contaminated with caffeine and other organic compounds that have physicochemical properties similar to those of caffeine.

  8. Acute genital ulcers

    PubMed Central

    Delgado-García, Silvia; Palacios-Marqués, Ana; Martínez-Escoriza, Juan Carlos; Martín-Bayón, Tina-Aurora

    2014-01-01

    Acute genital ulcers, also known as acute vulvar ulcers, ulcus vulvae acutum or Lipschütz ulcers, refer to an ulceration of the vulva or lower vagina of non-venereal origin that usually presents in young women, predominantly virgins. Although its incidence is unknown, it seems a rare entity, with few cases reported in the literature. Their aetiology and pathogenesis are still unknown. The disease is characterised by an acute onset of flu-like symptoms with single or multiple painful ulcers on the vulva. Diagnosis is mainly clinical, after exclusion of other causes of vulvar ulcers. The treatment is mainly symptomatic, with spontaneous resolution in 2 weeks and without recurrences in most cases. We present a case report of a 13-year-old girl with two episodes of acute ulcers that fit the clinical criteria for Lipschütz ulcers. PMID:24473429

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

    PubMed

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

    2012-01-01

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

  10. The cellular lesion of humoral rejection: predominant recruitment of monocytes to peritubular and glomerular capillaries.

    PubMed

    Fahim, T; Böhmig, G A; Exner, M; Huttary, N; Kerschner, H; Kandutsch, S; Kerjaschki, D; Bramböck, A; Nagy-Bojarszky, K; Regele, H

    2007-02-01

    Accumulation of inflammatory cells within capillaries is a common morphologic feature of humoral renal allograft rejection and is most easily appreciated if it occurs in glomeruli. The aim of our study was to determine the amount and composition of immune cells within glomeruli and peritubular capillaries (PTC) in cellular and humoral allograft rejection. Immunofluorescent double-labeling for CD31 and CD3 or CD68 was used for phenotyping and enumerating immune cells within glomeruli and PTC. The major findings are: (1) accumulation of immune cells in PTC is far more common than it would be anticipated based on the assessment by conventional histology; (2) it is not the absolute number of immune cells accumulating within capillaries, but rather the composition of the intracapillary cell population that distinguishes humoral rejection from cellular rejection and (3) in C4d positive biopsies a predominantly monocytic cell population accumulates not only within glomeruli but also within PTC. The median value of monocyte/T-cell ratio within PTC was 2.3 in C4d positive biopsies but only 1 (p = 0.0008) in C4d negative biopsies. Given their prominent presence within capillaries and their extensive biological versatility monocytes might contribute to the capillary damage observed in acute and chronic allograft rejection. PMID:17283488

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

    PubMed Central

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

    2012-01-01

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

  12. [Psychotic episode due to Hashimoto's thyroiditis].

    PubMed

    Nazou, M; Parlapani, E; Nazlidou, E-I; Athanasis, P; Bozikas, V P

    2016-01-01

    Thyroid hormones are crucial in adult brain metabolic activity. As a result, abnormal thyroid gland function and in particular hypofunction, might cause principally depression and neurocognitive dysfunction. Psychosis, presented mainly with thought disorders and perceptual disturbances, is a much rarer manifestation of hypothyreoidism. A correlation between hypothyreoidism and psychosis has been described since 1888, especially in cases of advanced hypothyreoidism. A few years later (1949), Asher first added the terminology "myxedema madness" to the literature. Psychotic symptoms typically appear after the onset of physical symptoms, usually with a delay of months or years. The case of a female patient who presented a psychotic episode as a first manifestation of hypothyroidism will be described. NE, a 48 yearold female patient, was admitted for the first time to an inpatient mental health care unit due to delusions of persecution and reference, as well as auditory hallucinations that appeared a few weeks ago. After the patient admission, routine laboratory examination was conducted. In order to relieve the patient from her sense of discomfort and while awaiting laboratory results, olanzapine, 5 mg/day, was administered. Neurological examination and cranial computed tomography scan were unremarkable. Hormonal laboratory tests though revealed severe low thyroid hormone levels. Thyroid antibody testing certified Hashimoto's thyroiditis. Olanzapine was discontinued and the patient received thyroid hormone substitution, levothyroxine 75 μg/day, instead. The patient was discharged showing a significant improvement of psychotic symptoms after a 12-day hospitalization. A month later the patient was reevaluated. She had fully recovered from the psychotic episode. A year later, the patient continues to remain free from psychiatric symptoms, while thyroid hormone levels have been restored within normal range. The patient continues receiving only thyroid hormone substitution

  13. Rejection of Cardiac Xenografts Transplanted from α 1,3-Galactosyltransferase Gene-Knockout (GalT-KO) Pigs to Baboons

    PubMed Central

    Hisashi, Y.; Yamada, K.; Kuwaki, K.; Tseng, Y.-L; Dor, F. J. M. F.; Houser, S. L; Robson, S. C.; Schuurman, H.-J.; Cooper, D. K. C.; Sachs, D. H.; Colvin, R. B.; Shimizu, A.

    2010-01-01

    The use of α 1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL+ graft cell injury with the infiltration of T cells (including CD3 and TIA-1+ cytotoxic T cells), CD4+ cells, CD8+ cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL+ dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens. PMID:19032222

  14. Acute bronchial asthma.

    PubMed

    Grover, Sudhanshu; Jindal, Atul; Bansal, Arun; Singhi, Sunit C

    2011-11-01

    Acute asthma is the third commonest cause of pediatric emergency visits at PGIMER. Typically, it presents with acute onset respiratory distress and wheeze in a patient with past or family history of similar episodes. The severity of the acute episode of asthma is judged clinically and categorized as mild, moderate and severe. The initial therapy consists of oxygen, inhaled beta-2 agonists (salbutamol or terbutaline), inhaled budesonide (three doses over 1 h, at 20 min interval) in all and ipratropium bromide and systemic steroids (hydrocortisone or methylprednisolone) in acute severe asthma. Other causes of acute onset wheeze and breathing difficulty such as pneumonia, foreign body, cardiac failure etc. should be ruled out with help of chest radiography and appropriate laboratory investigations in first time wheezers and those not responding to 1 h of inhaled therapy. In case of inadequate response or worsening, intravenous infusion of magnesium sulphate, terbutaline or aminophylline may be used. Magnesium sulphate is the safest and most effective alternative among these. Severe cases may need ICU care and rarely, ventilatory support. PMID:21769523

  15. SENSITIZATION AND TOLERANCE WITH EPISODIC (WEEKLY) NICOTINE ON MOTOR ACTIVITY IN RATS.

    EPA Science Inventory

    These studies grew out of an unexpected finding from investigations of the neurobehavioral toxicity of PCBs. This paper shows that episodic, or recurring intermittent acute exposures to nicotine produce dramatic and long-lasting changes in the motor activity of laboratory rats. ...

  16. History of abuse and risky sex among substance users: The role of rejection sensitivity and the need to belong.

    PubMed

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

    2016-11-01

    This study investigates abuse and rejection sensitivity as important correlates of risky sexual behavior in the context of substance use. Victims of abuse may experience heightened sensitivity to acute social rejection and consequently engage in risky sexual behavior in an attempt to restore belonging. Data were collected from 258 patients at a substance use treatment facility in Washington, D.C. Participants' history of abuse and risky sexual behavior were assessed via self-report. To test the mediating role of rejection sensitivity, participants completed a social rejection task (Cyberball) and responded to a questionnaire assessing their reaction to the rejection experience. General risk-taking propensity was assessed using a computerized lab measure. Abuse was associated with increased rejection sensitivity (B=0.124, SE=0.040, p=0.002), which was in turn associated with increased risky sex (B=0.06, SE=0.028, p=0.03) (indirect effect=0.0075, SE=0.0043; 95% CI [0.0006, 0.0178]), but not with other indices of risk-taking. These findings suggest that rejection sensitivity may be an important mechanism underlying the relationship between abuse and risky sexual behavior among substance users. These effects do not extend to other risk behaviors, supporting the notion that risky sex associated with abuse represents a means to interpersonal connection rather than a general tendency toward self-defeating behavior. PMID:27344009

  17. 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

  18. Low-Dose Rituximab Therapy for Antibody-Mediated Rejection in a Highly Sensitized Heart-Transplant Recipient

    PubMed Central

    Aggarwal, Ashim; Pyle, Joseph; Hamilton, John; Bhat, Geetha

    2012-01-01

    Antibody-mediated rejection is the B-cell–mediated production of immunoglobulin G antibody against the transplanted heart. The currently available therapies for antibody-mediated rejection have had marginal success, and chronic manifestations of rejection can result in an increased risk of graft vasculopathy and perhaps require repeat transplantation. Rituximab, a monoclonal antibody directed against the CD20 receptor of B-lymphocytes and approved as therapy for lymphoma, can be used in heart-transplant patients for the management of antibody-mediated rejection. We present the case of a 52-year-old woman with high allosensitization (pre-transplantation panel reactive antibody level, 72%) who underwent successful orthotopic heart transplantation. Postoperatively, her acute antibody-mediated rejection with concomitant cellular rejection was successfully treated with low-dose rituximab. The patient died 5 months later because of multiple other medical problems. The present case suggests a role for low-dose rituximab as therapy for antibody-mediated rejection in heart-transplant patients. PMID:23304051

  19. The temporal attributes of episodic memory.

    PubMed

    Kesner, Raymond P; Hunsaker, Michael R

    2010-12-31

    From a temporal dynamic processing point of view, episodic memory can be divided into three critical time periods: short-term episodic memory with a duration of seconds, intermediate-term episodic memory with a duration from minutes to hours, and long-term or remote episodic memory with a duration from days to years. We propose that short-term episodic memory is mediated by the CA3 subregion of the hippocampus, intermediate-term episodic memory is mediated by the CA1 subregion of the hippocampus (in certain situations aided by the CA3 subregion), and that long-term or remote episodic memory may be mediated by the CA1 subregion. In support of the above mentioned proposal data are presented to support the short-term and intermediate episodic memory functions of CA3 and CA1 based on single item object, spatial location, and object-place association tasks. Additional data are presented for a role for CA3 in short-term episodic memory based on multiple sequential spatial locations, visual objects, and odors tasks. The same episodic memory model based on duration mentioned above cannot easily be applied to the functions of the CA3 (short-term episodic) and CA1 (intermediate-term episodic) for a multiple sequentially presented item, such as a places, objects or odors. The reason for this is that the CA1 region supports, in addition to intermediate episodic memory, temporal pattern separation processes which would reduce interference among sequentially experienced items. The consequence is that this temporal pattern separation process can result in CA1 involvement in short-term episodic tasks based on duration. Also, data are presented based on tasks that involved multiple-trials tested within a day and between days short-term and intermediate-term episodic memory. Furthermore, the mechanisms for understanding the interactions and dissociations between CA3 and CA1 are discussed. The DG appears to have a modulatory influence on the CA3 and CA1 mediation of short-term and

  20. Episodic Accretion in Young Stars

    NASA Astrophysics Data System (ADS)

    Audard, M.; Ábrahám, P.; Dunham, M. M.; Green, J. D.; Grosso, N.; Hamaguchi, K.; Kastner, J. H.; Kóspál, Á.; Lodato, G.; Romanova, M. M.; Skinner, S. L.; Vorobyov, E. I.; Zhu, Z.

    In the last 20 years, the topic of episodic accretion has gained significant interest in the star-formation community. It is now viewed as a common, although still poorly understood, phenomenon in low-mass star formation. The FU Orionis objects (FUors) are long-studied examples of this phenomenon. FU Orionis objects are believed to undergo accretion outbursts during which the accretion rate rapidly increases from typically 10-7 to a few 10-4 M⊙ yr-1, and remains elevated over several decades or more. EXors, a loosely defined class of pre-main-sequence stars, exhibit shorter and repetitive outbursts, associated with lower accretion rates. The relationship between the two classes, and their connection to the standard pre-main-sequence evolutionary sequence, is an open question: Do they represent two distinct classes, are they triggered by the same physical mechanism, and do they occur in the same evolutionary phases? Over the past couple of decades, many theoretical and numerical models have been developed to explain the origin of FUor and EXor outbursts. In parallel, such accretion bursts have been detected at an increasing rate, and as observing techniques improve, each individual outburst is studied in increasing detail. We summarize key observations of pre-main-sequence star outbursts, and review the latest thinking on outburst triggering mechanisms, the propagation of outbursts from star/disk to disk/jet systems, the relation between classical EXors and FUors, and newly discovered outbursting sources — all of which shed new light on episodic accretion. We finally highlight some of the most promising directions for this field in the near- and long-term.

  1. Empirical typology of bipolar I mood episodes*

    PubMed Central

    Solomon, David A.; Leon, Andrew C.; Endicott, Jean; Coryell, William H.; Li, Chunshan; Fiedorowicz, Jess G.; Keller, Martin B.

    2009-01-01

    Background Much remains unknown about the phenomenology of bipolar I disorder. Aims To determine the type of bipolar I mood episodes that occur over time, and their relative frequency. Method A total of 219 individuals with Research Diagnostic Criteria bipolar I disorder were prospectively followed for up to 25 years (median 20 years). Psychopathology was assessed with the Longitudinal Interval Follow-up Evaluation. Results Overall, 1208 mood episodes were prospectively observed. The episodes were empirically classified as follows: major depression, 30.9% (n = 373); minor depression, 13.0% (n = 157); mania, 20.4% (n = 246); hypomania, 10.4% (n = 126); cycling, 17.3% (n = 210); cycling plus mixed state, 7.8% (n = 94); and mixed, 0.2% (n = 2). Conclusions Cycling episodes constituted 25% of all episodes. Work groups revising ICD–10 and DSM–IV should add a category for bipolar I cycling episode. PMID:19949203

  2. Solar dynamic space power system heat rejection

    NASA Technical Reports Server (NTRS)

    Carlson, A. W.; Gustafson, E.; Mclallin, K. L.

    1986-01-01

    A radiator system concept is described that meets the heat rejection requirements of the NASA Space Station solar dynamic power modules. The heat pipe radiator is a high-reliability, high-performance approach that is capable of erection in space and is maintainable on orbit. Results are present of trade studies that compare the radiator system area and weight estimates for candidate advanced high performance heat pipes. The results indicate the advantages of the dual-slot heat pipe radiator for high temperature applications as well as its weight-reduction potential over the range of temperatures to be encountered in the solar dynamic heat rejection systems.

  3. Neurometabolic correlates of depression and disability in episodic cluster headache

    PubMed Central

    Valet, Michael; Pfaffenrath, Volker; Boecker, Henning; Rüther, Katharina V.; Tölle, Thomas R.; Sprenger, Till

    2010-01-01

    A close association between pain, depression and disability has been shown. However, the neurometabolic correlates of this association have been barely investigated in disease states. Episodic cluster headache is a severe headache syndrome and represents a suitable disease model for the investigation of episodic pain. The aim of this study was to explore the relationship between depression and disability as well as pain scores and brain metabolism in patients with cluster headache during the disease period with repetitive pain attacks, but outside an acute attack. Thirteen patients with cluster headache underwent 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission (FDG-PET) and completed questionnaires on depression and disability as well as a pain visual analogue rating scale (VAS). A positive correlation between the depression scores and glucose metabolism was observed in the insular cortex. A positive correlation between the pain disability scores and brain metabolism was detected in the amygdala. The same applied to the pain visual analogue rating scores. Our data underline the association between severe episodic pain, depression and disability. In addition to this clinical observation, our results stress the importance of the insula and amygdala in pain processing and suffering. PMID:20737158

  4. Acute and dramatic saxophone penis.

    PubMed

    García-Rodrigo, Carlota Gutiérrez; Maroñas-Jiménez, Lidia; Menis, Diana; Larráin, Hugo; Martínez, Lara Angulo

    2015-01-01

    We present a case of intense genital swelling because of a hereditary angioedema. This rare disease should be included in the differential diagnosis of acute and asymptomatic genital edema, because it may prevent future potentially life-threatening episodes of visceral angioedema. PMID:26752411

  5. Changes in Self-Definition Impede Recovery From Rejection.

    PubMed

    Howe, Lauren C; Dweck, Carol S

    2016-01-01

    Previous research highlights how adept people are at emotional recovery after rejection, but less research has examined factors that can prevent full recovery. In five studies, we investigate how changing one's self-definition in response to rejection causes more lasting damage. We demonstrate that people who endorse an entity theory of personality (i.e., personality cannot be changed) report alterations in their self-definitions when reflecting on past rejections (Studies 1, 2, and 3) or imagining novel rejection experiences (Studies 4 and 5). Further, these changes in self-definition hinder post-rejection recovery, causing individuals to feel haunted by their past, that is, to fear the recurrence of rejection and to experience lingering negative affect from the rejection. Thus, beliefs that prompt people to tie experiences of rejection to self-definition cause rejection's impact to linger. PMID:26498977

  6. Development of enhanced sulfur rejection processes

    SciTech Connect

    Yoon, R.H.; Luttrell, G.H.; Adel, G.T.; Richardson, P.E.

    1996-03-01

    Research at Virginia Tech led to the development of two complementary concepts for improving the removal of inorganic sulfur from many eastern U.S. coals. These concepts are referred to as Electrochemically Enhanced Sulfur Rejection (EESR) and Polymer Enhanced Sulfur Rejection (PESR) processes. The EESR process uses electrochemical techniques to suppress the formation of hydrophobic oxidation products believed to be responsible for the floatability of coal pyrite. The PESR process uses polymeric reagents that react with pyrite and convert floatable middlings, i.e., composite particles composed of pyrite with coal inclusions, into hydrophilic particles. These new pyritic-sulfur rejection processes do not require significant modifications to existing coal preparation facilities, thereby enhancing their adoptability by the coal industry. It is believed that these processes can be used simultaneously to maximize the rejection of both well-liberated pyrite and composite coal-pyrite particles. The project was initiated on October 1, 1992 and all technical work has been completed. This report is based on the research carried out under Tasks 2-7 described in the project proposal. These tasks include Characterization, Electrochemical Studies, In Situ Monitoring of Reagent Adsorption on Pyrite, Bench Scale Testing of the EESR Process, Bench Scale Testing of the PESR Process, and Modeling and Simulation.

  7. Development of enhanced sulfur rejection processes

    SciTech Connect

    Yoon, R.H.; Luttrell, G.; Adel, G.; Richardson, P.E.

    1993-03-23

    Research at Virginia Tech led to two complementary concepts for improving the removal of inorganic sulfur from much of the Eastern US coals. One controls the surface properties of coal pyrite (FeS[sub 2]) by electrochemical-.potential control, referred to as the Electrochemically Enhanced Sulfur Rejection (EESR) Process: The second controls the flotation of middlings, i.e., particles composed of pyrite with coal inclusions by using polymeric reagents to react with pyrite and convert the middlings to hydrophilic particles, and is termed the Polymer Enhanced Sulfur Rejection (PESR) Process. These new concepts are based on recent research establishing the two main reasons why flotation fails to remove more than about 50% of the pyritic sulfur from coal: superficial oxidization of liberated pyrite to form polysulfide oxidation products so that a part of the liberated pyrite floats with the coal; and hydrophobic coal inclusions in the middlings dominating their flotation so that the middlings also float with the coal. These new pyritic-sulfur rejection processes do not require significant modifications of existing coal preparation facilities, enhancing their adoptability by the coal industry. It is believed that they can be used simultaneously to achieve both free pyrite and locked pyrite rejection.

  8. Nutrition: rejection is the fly's protection.

    PubMed

    Herbert, Samantha L; Ribeiro, Carlos

    2014-03-31

    Animals need to ingest a full set of essential amino acids through their diet. A new study in Drosophila larvae describes how activation of the kinase GCN2 in three dopaminergic neurons mediates the rejection of amino-acid-imbalanced food. PMID:24698377

  9. A Developmental Interpretation of Help Rejection.

    ERIC Educational Resources Information Center

    Silverman, Sharon; Juhasz, Anne M.

    1993-01-01

    Describes a study of factors accounting for low levels of student participation in academic assistance programs, based on case studies of eight university students on academic probation who had rejected offers of academic assistance, using structured interviews and the Erikson Psychosocial Stage Inventory and the Mooney Problem Checklist. Includes…

  10. Examining Social Acceptance & Rejection. FPG Snapshot #44

    ERIC Educational Resources Information Center

    FPG Child Development Institute, 2007

    2007-01-01

    This FPG Snapshot summarizes the findings of a study, published in the November 2006 issue of the "Journal of Educational Psychology," that examined whether children with disabilities are accepted or rejected by their classmates in inclusive classrooms. Specifically, the study examined two sets of related questions: (1) Are individual children…

  11. Antimyosin imaging in cardiac transplant rejection

    SciTech Connect

    Johnson, L.L.; Cannon, P.J. )

    1991-09-01

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

  12. Guidelines for proposals to conserve or reject

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The scientific journal Taxon is the medium for the publication of proposals to conserve or reject scientific names of plants based on the International Code of Botanical Nomenclature (ICBN). The first formal guidelines for the preparation of such proposals appeared in 1994; these were updated in 200...

  13. Capgras Syndrome in First-Episode Psychotic Disorders

    PubMed Central

    Salvatore, Paola; Bhuvaneswar, Chaya; Tohen, Mauricio; Khalsa, Hari-Mandir K.; Maggini, Carlo; Baldessarini, Ross J.

    2014-01-01

    Background Misidentification phenomena, including the delusion of “imposters” named after Joseph Capgras, occur in various major psychiatric and neurological disorders but have rarely been studied systematically in broad samples of modern patients. This study investigated the prevalence and correlated clinical factors of Capgras phenomenon in a broad sample of patient-subjects with first-lifetime episodes of psychotic affective and non affective disorders. Methods We evaluated 517 initially hospitalized, first-episode psychotic-disorder patients for prevalence of Capgras phenomenon and its association with DSM-IV-TR diagnoses including schizophreniform, brief psychotic, unspecified psychotic, delusional, and schizoaffective disorders, schizophrenia, bipolar-I disorder and major depression with psychotic features, and with characteristics of interest including antecedent psychiatric and neurological morbidity, onset-type and presenting psychopathological phenomena, using standard bivariate and multivariate statistical methods. Results Capgras syndrome was identified in 73/517 (14.1%) patients (8.2%–50% across diagnoses). Risk was greatest with acute or brief psychotic disorders (schizophreniform [50%], brief [34.8%], or unspecified [23.9%] psychoses), intermediate in major depression (15%), schizophrenia (11.4%) and delusional disorder (11.1%), and lowest in bipolar-I (10.3%) and schizoaffective disorders (8.2%). Associated were somatosensory, olfactory and tactile hallucinations, Schneiderian (especially delusional perception), and cycloid features as described by Perris and Brockington including polymorphous psychotic phenomena, rapidly shifting psychomotor and affective symptoms, pan-anxiety, ecstasy, over-concern with death, and perplexity or confusion, as well as rapid-onset, but not sex, age, abuse-history, dissociative features, or indications of neurological disorders. Conclusions Capgras syndrome was prevalent across a broad spectrum of first-episode

  14. Perinatal episodes across the mood disorder spectrum.

    PubMed

    Di Florio, Arianna; Forty, Liz; Gordon-Smith, Katherine; Heron, Jess; Jones, Lisa; Craddock, Nicholas; Jones, Ian

    2013-02-01

    CONTEXT Affective disorders are common in women, with many episodes having an onset in pregnancy or during the postpartum period. OBJECTIVE To investigate the occurrence and timing of perinatal mood episodes in women with bipolar I disorder, bipolar II disorder, and recurrent major depression (RMD). SETTING AND PATIENTS Women were recruited in our ongoing research on the genetic and nongenetic determinants of major affective disorders. Participants were interviewed and case notes were reviewed. Best-estimate diagnoses were made according to DSM-IV criteria. The 1785 parous women identified included 1212 women with bipolar disorder (980 with type I and 232 with type II) and 573 with RMD. Data were available on 3017 live births. MAIN OUTCOME MEASURES We report the lifetime occurrence of perinatal mood episodes, the rates of perinatal episodes per pregnancy/postpartum period, and the timing of the onset of episodes in relation to delivery. RESULTS More than two-thirds of all diagnostic groups reported at least 1 lifetime episode of illness during pregnancy or the postpartum period. Women with bipolar I disorder reported an approximately 50% risk of a perinatal major affective episode per pregnancy/postpartum period. Risks were lower in women with RMD or bipolar II disorder, at approximately 40% per pregnancy/postpartum period. Mood episodes were significantly more common in the postpartum period in bipolar I disorder and RMD. Most perinatal episodes occurred within the first postpartum month, with mania or psychosis having an earlier onset than depression. CONCLUSIONS Although episodes of postpartum mood disorder are more common in bipolar I disorder and manic and psychotic presentations occur earlier in the postpartum period, perinatal episodes are highly prevalent across the mood disorder spectrum. PMID:23247604

  15. 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

  16. HLA variants related to primary sclerosing cholangitis influence rejection after liver transplantation

    PubMed Central

    Fosby, Bjarte; Næss, Sigrid; Hov, Johannes R; Traherne, James; Boberg, Kirsten M; Trowsdale, John; Foss, Aksel; Line, Pål-Dag; Franke, Andre; Melum, Espen; Scott, Helge; Karlsen, Tom H

    2014-01-01

    AIM: To investigate influence of human leukocyte antigen (HLA) and killer immunoglobuline-like receptor (KIR) genotypes on risks of acute rejection (AR) after liver transplantation (LTX). METHODS: In this retrospective study we included 143 adult donor-recipient pairs with a minimum of 6 mo follow-up after LTX for whom DNA was available from both donor and recipients. Clinical data, all early complications including episodes and severity of AR and graft/patient survival were registered. The diagnosis of AR was based on clinical, biochemical and histological criteria. All suspected episodes of AR were biopsy confirmed. Key classical HLA loci (HLA-A, HLA-B, HLA-C and HLA-DRB1) were genotyped using Sanger sequencing. 16 KIR genes were genotyped using a novel real time PCR approach which allows for determination of the diploid copy number of each KIR gene. Immunohistochemical staining for T (CD3), B (CD20) and natural killer (NK) cells (CD56 and CD57) were performed on liver biopsies from 3 different patient groups [primary sclerosing cholangitis (PSC), primary biliary cirrhosis and non-autoimmune liver disease], 10 in each group, with similar grade of AR. RESULTS: Fourty-four (31%) patients were transplanted on the basis of PSC, 40% of them had AR vs 24% in the non-PSC group (P = 0.04). No significant impact of donor-recipient matching for HLA and KIR genotypes was detected. In the overall recipient population an increased risk of AR was detected for HLA-B*08 (P = 0.002, OR = 2.5; 95%CI: 1.4-4.6), HLA-C*07 (P = 0.001, OR = 2.4; 95%CI: 1.4-4.0) and HLA-DRB1*03 (P = 0.03, OR = 1.9; 95%CI: 1.0-3.3) and a decreased risk for HLA-DRB1*04 (P = 0.001, OR = 0.2; 95%CI: 0.1-0.5). For HLA-B*08, HLA-C*07 and DRB1*04 the associations remained evident in a subgroup analysis of non-PSC recipients (P = 0.04, P = 0.003 and P = 0.02, respectively). In PSC recipients corresponding P values were 0.002, 0.17 and 0.01 for HLA-B*08, HLA-C*07 and DRB1*04, respectively. A dosage effect of AR

  17. A Transactional Approach to Transfer Episodes

    ERIC Educational Resources Information Center

    Jornet, Alfredo; Roth, Wolff-Michael; Krange, Ingeborg

    2016-01-01

    In this article we present an analytical framework for approaching transfer episodes--episodes in which participants declare or can be declared to bring prior experience to bear on the current task organization. We build on Dewey's writings about the continuity of experience, Vygotsky's ideas of unit analysis, as well as more recent developments…

  18. Tracking the Construction of Episodic Future Thoughts

    ERIC Educational Resources Information Center

    D'Argembeau, Arnaud; Mathy, Arnaud

    2011-01-01

    The ability to mentally simulate possible futures ("episodic future thinking") is of fundamental importance for various aspects of human cognition and behavior, but precisely how humans construct mental representations of future events is still essentially unknown. We suggest that episodic future thoughts consist of transitory patterns of…

  19. Binding of episodic memories in the rat

    PubMed Central

    Crystal, Jonathon D.; Smith, Alexandra E.

    2014-01-01

    Summary People remember an event as a coherent scene [1-4]. Memory of such an episode is thought to reflect binding of a fully integrated representation, rather than memory of unconnected features [4-7]. However, it is not known if rodents form bound representations. Here we show that rats remember episodes as bound representations. Rats were presented with multiple features of unique episodes at memory encoding: what (food flavor), where (maze location), source (self-generated food seeking–running to the food site– or experimenter-generated food seeking –placement by the experimenter at the food site), and context (spatial cues in the room where the event occurred). After a delay, the trial continued with a memory assessment in which one flavor replenished at the self-generated- but not at experimenter-generated-locations. We presented rats with multiple overlapping features, in rapid succession, to ensure that successful memory retrieval required them to disambiguate multiple study episodes (using two rooms). We found that binding is resistant to interference from highly similar episodes and survives long retention intervals (~1 week). Our results suggest that multiple episodic memories are each structured as bound representations, which suggests that nonhumans represent episodic memories using a structure similar to that of people. This finding enhances the translational potential for utilizing animal models of episodic memory to explore the biological mechanisms of memory and validate therapeutic approaches for treating disorders of memory. PMID:25466681

  20. Episodic plate tectonics on Venus

    NASA Technical Reports Server (NTRS)

    Turcotte, Donald

    1992-01-01

    Studies of impact craters on Venus from the Magellan images have placed important constraints on surface volcanism. Some 840 impact craters have been identified with diameters ranging from 2 to 280 km. Correlations of this impact flux with craters on the Moon, Earth, and Mars indicate a mean surface age of 0.5 +/- 0.3 Ga. Another important observation is that 52 percent of the craters are slightly fractured and only 4.5 percent are embayed by lava flows. These observations led researchers to hypothesize that a pervasive resurfacing event occurred about 500 m.y. ago and that relatively little surface volcanism has occurred since. Other researchers have pointed out that a global resurfacing event that ceased about 500 MYBP is consistent with the results given by a recent study. These authors carried out a series of numerical calculations of mantle convection in Venus yielding thermal evolution results. Their model considered crustal recycling and gave rapid planetary cooling. They, in fact, suggested that prior to 500 MYBP plate tectonics was active in Venus and since 500 MYBP the lithosphere has stabilized and only hot-spot volcanism has reached the surface. We propose an alternative hypothesis for the inferred cessation of surface volcanism on Venus. We hypothesize that plate tectonics on Venus is episodic. Periods of rapid plate tectonics result in high rates of subduction that cool the interior resulting in more sluggish mantle convection.

  1. Urinary Cell mRNA Profiles and Differential Diagnosis of Acute Kidney Graft Dysfunction

    PubMed Central

    Matignon, Marie; Ding, Ruchuang; Dadhania, Darshana M.; Mueller, Franco B.; Hartono, Choli; Snopkowski, Catherine; Li, Carol; Lee, John R.; Sjoberg, Daniel; Seshan, Surya V.; Sharma, Vijay K.; Yang, Hua; Nour, Bakr; Vickers, Andrew J.; Suthanthiran, Manikkam

    2014-01-01

    Noninvasive tests to differentiate the basis for acute dysfunction of the kidney allograft are preferable to invasive allograft biopsies. We measured absolute levels of 26 prespecified mRNAs in urine samples collected from kidney graft recipients at the time of for-cause biopsy for acute allograft dysfunction and investigated whether differential diagnosis of acute graft dysfunction is feasible using urinary cell mRNA profiles. We profiled 52 urine samples from 52 patients with biopsy specimens indicating acute rejection (26 acute T cell–mediated rejection and 26 acute antibody-mediated rejection) and 32 urine samples from 32 patients with acute tubular injury without acute rejection. A stepwise quadratic discriminant analysis of mRNA measures identified a linear combination of mRNAs for CD3ε, CD105, TLR4, CD14, complement factor B, and vimentin that distinguishes acute rejection from acute tubular injury; 10-fold cross-validation of the six-gene signature yielded an estimate of the area under the curve of 0.92 (95% confidence interval, 0.86 to 0.98). In a decision analysis, the six-gene signature yielded the highest net benefit across a range of reasonable threshold probabilities for biopsy. Next, among patients diagnosed with acute rejection, a similar statistical approach identified a linear combination of mRNAs for CD3ε, CD105, CD14, CD46, and 18S rRNA that distinguishes T cell–mediated rejection from antibody-mediated rejection, with a cross-validated estimate of the area under the curve of 0.81 (95% confidence interval, 0.68 to 0.93). Incorporation of these urinary cell mRNA signatures in clinical decisions may reduce the number of biopsies in patients with acute dysfunction of the kidney allograft. PMID:24610929

  2. Adolescent social rejection alters pain processing in a CB1 receptor dependent manner.

    PubMed

    Schneider, Peggy; Pätz, Monique; Spanagel, Rainer; Schneider, Miriam

    2016-07-01

    Experiences of social rejection represent a major source of distress and in particular peer rejection during adolescence has been implicated in various psychiatric disorders. Moreover, experimentally induced acute social rejection alters pain perception in humans, implicating overlapping neurocircuits for social and physical pains. We recently demonstrated that rearing of adolescent Wistar rats with inadequate, less playful play partners (Fischer 344) persistently decreases pain sensitivity, although the detailed mechanisms mediating the aversiveness during the social encounter remained unsettled. With the present study we examined the behavioral performance during acute interaction of female adolescent Wistar rats with either age-matched same-strain partners or rats from the Fischer 344 strain. We here identify the low responsiveness upon playful attacks, which appears to be characteristic for social play in the Fischer 344 strain, as one of the main aversive components for adolescent Wistar animals during cross-strain encounters, which subsequently diminishes thermal pain reactivity. A detailed behavioral analysis further revealed increased ultrasonic vocalization at 50kHz and an increased frequency of playful attacks for adolescent Wistar animals paired with a Fischer 344 rat compared to same-strain control pairs. Finally, an acute injection of a subthreshold dose of the cannabinoid type 1 receptor inverse agonist/antagonist SR141716 before the social encounter abolished enhanced play-soliciting behavior in Wistar/Fischer 344 pairs as well as the behavioral consequences of the rejection experience in adolescent Wistar rats, further emphasizing an important modulatory role of the endocannabinoid system in mediating the effects of social behavior and social pain. PMID:27157075

  3. Episodic-like memory in animals

    PubMed Central

    Crystal, Jonathon D.

    2010-01-01

    Episodic memory consists of representations of unique past events. It has been argued that episodic memory is grounded in a temporal framework, meaning that we remember when an event occurred. The ability to model the temporal aspects of episodic memory in non-human animals has been challenging and controversial. This article briefly reviews the theoretical perspective in which temporal processing plays a prominent role in episodic memory. Next, the article reviews experimental attempts to identify temporal processes of episodic memory in animals. Recent studies suggest that, at the time of memory assessment, rats remember a unique earlier event, including when it occurred, what happened, and where it took place, referred to as what-where-when memory. PMID:20211205

  4. Pharmacotherapy of cancer-related episodic pain.

    PubMed

    Zeppetella, Giovambattista; Ribeiro, Maria D C

    2003-04-01

    Episodic pain is a transient increase in pain intensity over background pain. Episodic pain occurs commonly in cancer patients; it is a heterogeneous phenomenon that is incapacitating, debilitating and can have a significant impact on quality of life. Episodic pain can be difficult to manage; it is often unpredictable, typically of fast onset, of short duration and feels similar to background pain except that it may be more severe. The successful management of episodic pain can only be achieved following a thorough assessment. The subsequent management usually involves both pharmacological and non-pharmacological strategies integrated into the overall care and appropriate for the stage of the patient's disease. Pharmacological management includes the implementation of primary therapies (e.g., chemotherapy for the underlying aetiology of the pain, optimising the scheduled medication (e.g., analgesics and adjuvant analgesics) and specific pharmacological interventions for the episodic pain (e.g., rescue medication). PMID:12667112

  5. Serum albumin level during intestinal exfoliative rejection: a potential predictor of graft recovery and patient outcome.

    PubMed

    Zambernardi, Agustina; Gondolesi, Gabriel; Cabanne, Ana; Martinez, María I; Solar, Héctor; Rumbo, Martín; Rumbo, Carolina

    2013-01-01

    Exfoliative rejection is a severe complication after intestinal transplant. The assessment of mucosa histology is restricted to the area reached by endoscopy. We aim to evaluate the serum albumin (SA) value as a parameter of graft damage and clinical prognosis in intestinal exfoliative rejection (ExR). The present study is a retrospective analysis of 11 episodes of ExR occurred in a cohort of 26 patients. SA levels were measured 24 h after diagnosis and twice a week thereafter and then correlated with parameters of clinical and graft histological recovery (HR). During ExR, all patients had very low SA levels, reaching a minimum average of 1.9 ± 0.3 g/dL. According to the value of albumin levels at ExR diagnosis, the patients were grouped finding a correlation with their clinical evolution. Six ExR episodes presented with severe hipoalbuminemia (<2.2 g/dL; p < 0.05) that correlated with worse patient and graft outcome, ranging from graft loss and need for re-transplantation to delayed clinical and HR. SA at ExR diagnosis may be an indicator of the severity of the ExR process, and it could also be used as an early predictor of patient and graft outcome. PMID:23351092

  6. A single bout of resistance exercise can enhance episodic memory performance

    PubMed Central

    Weinberg, Lisa; Hasni, Anita; Shinohara, Minoru; Duarte, Audrey

    2014-01-01

    Acute aerobic exercise can be beneficial to episodic memory. This benefit may occur because exercise produces a similar physiological response as physical stressors. When administered during consolidation, acute stress, both physical and psychological, consistently enhances episodic memory, particularly memory for emotional materials. Here we investigated whether a single bout of resistance exercise performed during consolidation can produce episodic memory benefits 48 hours later. We used a one-leg knee extension/flexion task for the resistance exercise. To assess the physiological response to the exercise, we measured salivary alpha amylase (a biomarker of central norepinephrine), heart rate, and blood pressure. To test emotional episodic memory, we used a remember-know recognition memory paradigm with equal numbers of positive, negative, and neutral IAPS images as stimuli. The group that performed the exercise, the active group, had higher overall recognition accuracy than the group that did not exercise, the passive group. We found a robust effect of valence across groups, with better performance on emotional items as compared to neutral items and no difference between positive and negative items. This effect changed based on the physiological response to the exercise. Within the active group, participants with a high physiological response to the exercise were impaired for neutral items as compared to participants with a low physiological response to the exercise. Our results demonstrate that a single bout of resistance exercise performed during consolidation can enhance episodic memory and that the effect of valence on memory depends on the physiological response to the exercise. PMID:25262058

  7. Rejection Sensitivity Moderates the Impact of Rejection on Self-Concept Clarity

    PubMed Central

    Ayduk, Özlem; Gyurak, Anett; Luerssen, Anna

    2014-01-01

    Self-concept clarity (SCC) refers to the extent to which self-knowledge is clearly and confidently defined, internally consistent, and temporally stable. Research shows that SCC can be undermined by failures in valued goal domains. Because preventing rejection is an important self-relevant goal for people high in rejection sensitivity (RS), it is hypothesized here that failures to attain this goal would cause them to experience diminished SCC. Study 1, an experimental study, showed that high-RS people’s SCC was undermined following rejection but not following an aversive experience unrelated to rejection. Study 2, a daily diary study of couples in relationships, used occurrence of partner conflicts to operationalize rejection. Replicating the findings in Study 1, having a conflict on any given diary day predicted a greater reduction in the SCC of high- compared to low-RS people on the following day. The implications for understanding the conditions under which rejection negatively affects the self-concept are discussed. PMID:19713567

  8. Aerosol characteristics of different types of episode.

    PubMed

    Kuo, Chung-Yih; Lin, Yan-Ruei; Chang, Shih-Yu; Lin, Chuan-Yao; Chou, Chun-Hung

    2013-12-01

    Daily and hourly average data from nine air-quality monitoring stations distributed across central Taiwan, which include ten items (i.e., PM₁₀, PM₂.₅, wind direction, wind speed, temperature, relative humidity, SO₂, NO₂, NO, and CO), were collected from 2005 to 2009. Four episode types: long-range transport with dust storms (DS), long-range transport with frontal pollution (FP), river dust (RD), and stagnant weather (SW), and one mixed type of episode were identified. Of these four episode types, the SW was the dominant type, averaging about 70%. The mean ratio of PM₂.₅/PM₁₀ was the lowest during the RD episodes (0.42), while the mean ratio of PM₂.₅/PM₁₀ was the highest during the SW episodes (0.64). Fine aerosol (PM₂.₅) and coarse aerosol (PM₁₀-₂.₅) samples were collected by high-volume samplers for chemical composition analysis, from only three stations (Douliou, Lunbei, and Siansi) during the days of SW, RD, DS, and FP. The concentrations of PM₂.₅ and three ionic species (NH₄⁺, NO₃⁻, and SO₄²⁻) all showed significant differences among the four episode types. The highest levels of NO₃⁻ (12.1 μg/m(3)) and SO₄²⁻ (20.5 μg/m(3)) were found during the SW and FP episodes, respectively. A comparison on the spatial similarity of aerosol compositions among the episodes and/or non-episodes (control) was characterized by the coefficient of divergence (CD). The results showed higher CD values in PM₁₀-₂.₅ than in PM₂.₅, and the CD values between RD episodes and the other three episodes were higher than those between two types of episode for the other three episodes. The ratios of SOR (sulfur oxidation ratio), SO₄²⁻/EC (elemental carbon), NOR (nitrogen oxidation ratio), and NO₃⁻/EC showed that sulfate formation was most rapid during the FP, while nitrate formation was most rapid during the SW. PMID:23761164

  9. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  10. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  11. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  12. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  13. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT... Rejection of bids....

  14. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN... 2414.404 Rejection of bids....

  15. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN... 2414.404 Rejection of bids....

  16. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN... 2414.404 Rejection of bids....

  17. 48 CFR 2414.404 - Rejection of bids.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Rejection of bids. 2414.404 Section 2414.404 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN... 2414.404 Rejection of bids....

  18. How do episodic and semantic memory contribute to episodic foresight in young children?

    PubMed Central

    Martin-Ordas, Gema; Atance, Cristina M.; Caza, Julian S.

    2014-01-01

    Humans are able to transcend the present and mentally travel to another time, place, or perspective. Mentally projecting ourselves backwards (i.e., episodic memory) or forwards (i.e., episodic foresight) in time are crucial characteristics of the human memory system. Indeed, over the past few years, episodic memory has been argued to be involved both in our capacity to retrieve our personal past experiences and in our ability to imagine and foresee future scenarios. However, recent theory and findings suggest that semantic memory also plays a significant role in imagining future scenarios. We draw on Tulving’s definition of episodic and semantic memory to provide a critical analysis of their role in episodic foresight tasks described in the developmental literature. We conclude by suggesting future directions of research that could further our understanding of how both episodic memory and semantic memory are intimately connected to episodic foresight. PMID:25071690

  19. Mechanisms of allograft rejection of corneal endothelium

    SciTech Connect

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

    1982-07-01

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

  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. PMID:16283489

  1. Episodic acidification of small streams in the northeastern united states: ionic controls of episodes

    USGS Publications Warehouse

    Wigington, P.J., Jr.; DeWalle, David R.; Murdoch, Peter S.; Kretser, W.A.; Simonin, H.A.; Van Sickle, J.; Baker, J.P.

    1996-01-01

    As part of the Episodic Response Project (ERP), we intensively monitored discharge and stream chemistry of 13 streams located in the Northern Appalachian region of Pennsylvania and in the Catskill and Adirondack Mountains of New York from fall 1988 to spring 1990. The ERP clearly documented the occurrence of acidic episodes with minimum episodic pH ??? 5 and inorganic monomeric Al (Alim) concentrations >150 ??g/L in at least two study streams in each region. Several streams consistently experienced episodes with maximum Alim concentrations >350 ??g/L. Acid neutralizing capacity (ANC) depressions resulted from complex interactions of multiple ions. Base cation decreases often made the most important contributions to ANC depressions during episodes. Organic acid pulses were also important contributors to ANC depressions in the Adirondack streams, and to a lesser extent, in the Catskill and Pennsylvania streams. Nitrate concentrations were low in the Pennsylvania streams, whereas the Catskill and Adirondack study streams had high NO3- concentrations and large episodic pulses (???54 ??eq/L). Most of the Pennsylvania study streams also frequently experienced episodic pulses of SO42- (???78 ??eq/L), whereas the Adirondack and Catskill streams did not. High baseline concentrations of SO42- (all three study areas) and NO3- (Adirondacks and Catskills) reduced episodic minimum ANC, even when these ions did not change during episodes. The ion changes that controlled the most severe episodes (lowest minimum episodic ANC) differed from the ion changes most important to smaller, more frequent episodes. Pulses of NO3- (Catskills and Adirondacks), SO42- (Pennsylvania), or organic acids became more important during major episodes. Overall, the behavior of streamwater SO42- and NO4- is an indicator that acidic deposition has contributed to the severity of episodes in the study streams.

  2. Optical communication noise rejection using corelated photons

    NASA Technical Reports Server (NTRS)

    Jackson, D.; Hockney, G. M.; Dowling, J. P.

    2002-01-01

    This paper describes a completely new way to perform noise rejection using photons correlated through quantum entanglement to improve an optical communications link in the presence of uncorrelated noise. In particular, a detailed analysis is made of the case where a classical link would be saturated by an intense background, such as when a satellite is in front of the sun, and identifies where the quantum correlating system has superior performance.

  3. Funding for NSF underground laboratory is rejected

    SciTech Connect

    Kramer, David

    2011-02-15

    The Deep Underground Science and Engineering Laboratory (DUSEL), which proponents hope could provide a niche for the US particle-physics community, faces a shutdown as early as 1 April; the National Science Board (NSB) has rejected $19 million in funding needed to keep the project going through the fall of this year. The lab is housed in a disused gold mine in South Dakota's Black Hills.

  4. Episodic Memories and Their Relevance for Psychoactive Drug Use and Addiction

    PubMed Central

    Müller, Christian P.

    2013-01-01

    The majority of adult people in western societies regularly consume psychoactive drugs. While this consumption is integrated in everyday life activities and controlled in most consumers, it may escalate and result in drug addiction. Non-addicted drug use requires the systematic establishment of highly organized behaviors, such as drug-seeking and -taking. While a significant role for classical and instrumental learning processes is well established in drug use and abuse, declarative drug memories have largely been neglected in research. Episodic memories are an important part of the declarative memories. Here a role of episodic drug memories in the establishment of non-addicted drug use and its transition to addiction is suggested. In relation to psychoactive drug consumption, episodic drug memories are formed when a person prepares for consumption, when the drug is consumed and, most important, when acute effects, withdrawal, craving, and relapse are experienced. Episodic drug memories are one-trial memories with emotional components that can be much stronger than “normal” episodic memories. Their establishment coincides with drug-induced neuronal activation and plasticity. These memories may be highly extinction resistant and influence psychoactive drug consumption, in particular during initial establishment and at the transition to “drug instrumentalization.” In that, understanding how addictive drugs interact with episodic memory circuits in the brain may provide crucial information for how drug use and addiction are established. PMID:23734106

  5. Episodicity in back-arc tectonic regimes

    NASA Astrophysics Data System (ADS)

    Clark, Stuart R.; Stegman, Dave; Müller, R. Dietmar

    2008-12-01

    The evolution of back-arc basins is tied to the development of the dynamics of the subduction system they are a part of. We present a study of back-arc basins and model their development by implementing 3D time-dependant computer models of subduction including an overriding plate. We define three types of episodicity: pseudo-, quasi- and hyper-episodicity, and find evidence of these in nature. Observations of back-arc basin ages, histories of spreading, quiescence and compression in the overriding plate give us an understanding of the time-development of these subduction zones and back-arc basins. Across the globe today, a number of trenches are advancing—the Izu-Bonin Trench, the Mariana Trench, the Japan Trench, the Java-Sunda Trench and the central portion of the Peru-Chile Trench (the Andes subduction zone). The Izu-Bonin, Mariana and Japan all have established back-arc basins, while the others have documented episodes of spreading, quiescence, compression or a combination of these. The combination of advancing and retreating trench motion places these subduction zones in the category of hyper-episodicity. Quasi-episodicity, in which the back-arc shifts between phases of rifting, spreading and quiescence, is the dominant form of episodic back-arc development in the present. We find this type of episodicity in models for which the system is dynamically consistent—that we have allowed the subducting plate's velocity to be determined by the sinking slabs' buoyancy. Quasi- and hyper-episodicity are only found in subduction zones with relatively high subducting plate velocities, between 6 and 9 cm/year. Finally, those subduction zones for which the subducting plate is moving slowly, such as in the Mediterranean or the Scotia Sea, experience only pseudo-episodicity, where the spreading moves linearly towards the trench but often does so in discrete ridge-jump events.

  6. Aging, Estrogens, and Episodic Memory in Women

    PubMed Central

    Henderson, Victor W.

    2009-01-01

    Objective To review the relation in midlife and beyond between estrogen exposures and episodic memory in women. Background Episodic memory performance declines with usual aging, and impairments in episodic memory often portend the development of Alzheimer's disease. In the laboratory, estradiol influences hippocampal function and animal learning. However, it is controversial whether estrogens affect memory after a woman's reproductive years. Method Focused literature review, including a summary of a systematic search of clinical trials of estrogens in which outcomes included an objective measure of episodic memory. Results The natural menopause transition is not associated with objective changes in episodic memory. Strong clinical trial evidence indicates that initiating estrogen-containing hormone therapy after about age 60 years does not benefit episodic memory. Clinical trial findings in middle-age women before age 60 are limited by smaller sample sizes and shorter treatment durations, but these also do not indicate substantial memory effects. Limited short-term evidence, however, suggests that estrogens may improve verbal memory after surgical menopause. Although hormone therapy initiation in old age increases dementia risk, observational studies raise the question of an early critical window during which midlife estrogen therapy reduces late-life Alzheimer's disease. However, almost no data address whether midlife estrogen therapy affects episodic memory in old age. Conclusions Episodic memory is not substantially impacted by the natural menopause transition or improved by use of estrogen-containing hormone therapy after age 60. Further research is needed to determine whether outcomes differ after surgical menopause or whether episodic memory later in life is modified by midlife estrogenic exposures. PMID:19996872

  7. Active disturbance rejection controller for chemical reactor

    SciTech Connect

    Both, Roxana; Dulf, Eva H.; Muresan, Cristina I.

    2015-03-10

    In the petrochemical industry, the synthesis of 2 ethyl-hexanol-oxo-alcohols (plasticizers alcohol) is of high importance, being achieved through hydrogenation of 2 ethyl-hexenal inside catalytic trickle bed three-phase reactors. For this type of processes the use of advanced control strategies is suitable due to their nonlinear behavior and extreme sensitivity to load changes and other disturbances. Due to the complexity of the mathematical model an approach was to use a simple linear model of the process in combination with an advanced control algorithm which takes into account the model uncertainties, the disturbances and command signal limitations like robust control. However the resulting controller is complex, involving cost effective hardware. This paper proposes a simple integer-order control scheme using a linear model of the process, based on active disturbance rejection method. By treating the model dynamics as a common disturbance and actively rejecting it, active disturbance rejection control (ADRC) can achieve the desired response. Simulation results are provided to demonstrate the effectiveness of the proposed method.

  8. Current and future challenges in therapy for antibody-mediated rejection.

    PubMed

    Nair, Nandini; Ball, Timothy; Uber, Patricia A; Mehra, Mandeep R

    2011-06-01

    Antibody-mediated rejection (AMR) continues to present a challenge for the survival of the cardiac allograft. AMR appears to be on the rise, likely secondary to changing trends in clinical practice, including selection of patients for transplantation on mechanical circulatory support and development of more effective combinations of immunosuppressive drugs against acute cellular rejection. Most current strategies are aimed at treating acute AMR, but the treatment of chronic AMR is still not well defined. Clinically, AMR can often be more severe than cellular rejection and more difficult to treat, often not responding to typical protocols of increased immunosuppression. Complex steps involved in the antibody response allows for several potential targets for therapeutic intervention, including suppression of T and B cells, elimination of circulating antibodies, and inhibition of residual antibodies. Existing evidence suggests a multiregimen approach is the best option. Sustenance of accommodation and induction of tolerance could be viewed as viable options if adequate immune surveillance can be achieved in this setting. This review discusses the challenges in treating AMR and provides a critical analysis of current and possible future therapies. PMID:21474341

  9. Acute and chronic poisoning from residential exposures to elemental mercury--Michigan, 1989-1990

    SciTech Connect

    Not Available

    1991-06-14

    From May 1989 through November 1990, eight episodes of elemental mercury exposure in private residences or schools in the United States were reported to the Agency for Toxic Substances and Disease Registry (ATSDR). The case studies in this report document two of these episodes (both in Michigan) of residential mercury poisoning--one involving acute mercury exposure, and the other, chronic exposure to elemental mercury. These episodes illustrate the differing clinical and toxicologic manifestations of acute and chronic mercury poisoning.

  10. Effect of Heat Rejection Conditions on Cryocooler Operational Stability

    NASA Technical Reports Server (NTRS)

    Ross, R. G., Jr.; Johnson, D. L.

    1997-01-01

    It is well known that cryocooler thermal efficiency is a strong function of heat rejection temperature, roughly following the dependency described by carnot. An equally important and generally overlooked implication of cryocooler heat-rejection thermodynamics is the effect of the heat rejection temparature control mode on cyrocooler performance and operational stability.

  11. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 8 2014-10-01 2014-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  12. 7 CFR 56.24 - Rejection of application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Rejection of application. 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application. (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  13. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2013-01-01 2013-01-01 false Approval or rejection. 1956.84 Section...

  14. 18 CFR 154.5 - Rejection of filings.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Rejection of filings. 154.5 Section 154.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Conditions § 154.5 Rejection of filings. A filing that fails to comply with this part may be rejected by...

  15. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 8 2013-10-01 2013-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  16. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  17. 18 CFR 154.5 - Rejection of filings.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Rejection of filings. 154.5 Section 154.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Conditions § 154.5 Rejection of filings. A filing that fails to comply with this part may be rejected by...

  18. 18 CFR 154.5 - Rejection of filings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Rejection of filings. 154.5 Section 154.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Conditions § 154.5 Rejection of filings. A filing that fails to comply with this part may be rejected by...

  19. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  20. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  1. 18 CFR 50.8 - Acceptance/rejection of applications.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Acceptance/rejection of... ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be... chapter. This rejection is without prejudice to an applicant's refiling a complete application....

  2. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  3. 18 CFR 154.5 - Rejection of filings.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Rejection of filings. 154.5 Section 154.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Conditions § 154.5 Rejection of filings. A filing that fails to comply with this part may be rejected by...

  4. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  5. 7 CFR 56.24 - Rejection of application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Rejection of application. 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application. (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  6. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  7. 37 CFR 1.113 - Final rejection or action.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Final rejection or action. 1... Applicant and Further Consideration § 1.113 Final rejection or action. (a) On the second or any subsequent examination or consideration by the examiner the rejection or other action may be made final,...

  8. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2014-01-01 2014-01-01 false Approval or rejection. 1956.84 Section...

  9. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  10. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  11. 37 CFR 1.113 - Final rejection or action.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Final rejection or action. 1... Applicant and Further Consideration § 1.113 Final rejection or action. (a) On the second or any subsequent examination or consideration by the examiner the rejection or other action may be made final,...

  12. 18 CFR 50.8 - Acceptance/rejection of applications.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Acceptance/rejection of... ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be... chapter. This rejection is without prejudice to an applicant's refiling a complete application....

  13. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 8 2012-10-01 2012-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  14. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  15. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 8 2011-10-01 2011-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  16. When Is Peer Rejection Justifiable? Children's Understanding across Two Cultures

    ERIC Educational Resources Information Center

    Park, Yoonjung; Killen, Melanie

    2010-01-01

    This study investigated how Korean (N = 397) and U.S. (N = 333) children and adolescents (10 and 13 years of age) evaluated personality (aggression, shyness) and group (gender, nationality) characteristics as a basis for peer rejection in three contexts (friendship rejection, group exclusion, victimization). Overall, peer rejection based on "group…

  17. 18 CFR 50.8 - Acceptance/rejection of applications.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Acceptance/rejection of... ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be... chapter. This rejection is without prejudice to an applicant's refiling a complete application....

  18. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  19. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  20. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2011-01-01 2011-01-01 false Approval or rejection. 1956.84 Section...

  1. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  2. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2012-01-01 2012-01-01 false Approval or rejection. 1956.84 Section...

  3. 49 CFR 1104.10 - Rejection of a deficient document.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Rejection of a deficient document. 1104.10 Section 1104.10 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION...-PLEADINGS, GENERALLY § 1104.10 Rejection of a deficient document. (a) The Board may reject a...

  4. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rejection of individual... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.404-2 Rejection... rejections, shall be preserved with the papers relating to the acquisition. (l) After submitting a bid,...

  5. 7 CFR 56.24 - Rejection of application.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Rejection of application. 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application. (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  6. 7 CFR 56.24 - Rejection of application

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Rejection of application 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  7. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... properly evaluate an offer is a compelling reason for rejection; however, the contracting officer...

  8. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Housing § 1956.84 Approval or rejection. (a)-(d) (e) Appeal rights. A debtor whose debt settlement offer is rejected will be notified of appeal rights pursuant to 7 CFR part 11. ... 7 Agriculture 14 2010-01-01 2009-01-01 true Approval or rejection. 1956.84 Section...

  9. 7 CFR 56.24 - Rejection of application

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rejection of application 56.24 Section 56.24... EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application (a) An... Administrator that prior commitments of the Department necessitate rejection of the application. (b) Each...

  10. 37 CFR 1.113 - Final rejection or action.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Final rejection or action. 1... Applicant and Further Consideration § 1.113 Final rejection or action. (a) On the second or any subsequent examination or consideration by the examiner the rejection or other action may be made final,...

  11. 7 CFR 1423.8 - Approval or rejection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Approval or rejection. 1423.8 Section 1423.8... WAREHOUSES § 1423.8 Approval or rejection. (a) CCC will notify warehouse operators approved under this part.... (b) CCC will notify the warehouse operator of rejection under this part in writing. The...

  12. Children's Coping with "In Vivo" Peer Rejection: An Experimental Investigation

    ERIC Educational Resources Information Center

    Reijntjes, Albert; Stegge, Hedy; Terwogt, Mark Meerum; Kamphuis, Jan Henk; Telch, Michael J.

    2006-01-01

    We examined children's behavioral coping in response to an "in vivo" peer rejection manipulation. Participants (N = 186) ranging between 10 and 13 years of age, played a computer game based on the television show "Survivor" and were randomized to either peer rejection (i.e., being voted out of the game) or non-rejection control. During a five-min.…

  13. Paying to belong: when does rejection trigger ingratiation?

    PubMed

    Romero-Canyas, Rainer; Downey, Geraldine; Reddy, Kavita S; Rodriguez, Sylvia; Cavanaugh, Timothy J; Pelayo, Rosemary

    2010-11-01

    Societies and social scientists have long held the belief that exclusion induces ingratiation and conformity, an idea in contradiction to robust empirical evidence linking rejection with hostility and aggression. The classic literatures on ingratiation and conformity help resolve this contradiction by identifying circumstances under which rejection may trigger efforts to ingratiate. Jointly, findings from these literatures suggest that when people are given an opportunity to impress their rejecters, ingratiation is likely after rejection experiences that are harsh and that occur in important situations that threaten the individual's self-definition. Four studies tested the hypothesis that people high in rejection sensitivity and therefore dispositionally concerned about rejection will utilize opportunities to ingratiate after harsh rejection in situations that are self-defining. In 3 studies of situations that are particularly self-defining for men, rejection predicted ingratiation among men (but not women) who were high in rejection sensitivity. In a 4th study, harsh rejection in a situation particularly self-defining for women predicted ingratiation among highly rejection-sensitive women (but not men). These findings help identify the specific circumstances under which people are willing to act in socially desirable ways toward those who have rejected them harshly. PMID:20649367

  14. 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

  15. 48 CFR 19.505 - Rejecting Small Business Administration recommendations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Rejecting Small Business... REGULATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 19.505 Rejecting Small Business Administration recommendations. (a) If the contracting officer rejects a...

  16. 48 CFR 19.505 - Rejecting Small Business Administration recommendations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rejecting Small Business... REGULATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 19.505 Rejecting Small Business Administration recommendations. (a) If the contracting officer rejects a...

  17. [Young person's first-episode psychosis].

    PubMed

    Mäki, Pirjo; Veijola, Juha

    2012-01-01

    Young person's first-episode psychosis may signify the onset of schizophrenia, psychotic depression or bipolar disorder. It can also be a brief condition resulting in full recovery. The psychosis may be caused by drugs. First-episode psychosis is usually preceded by a long period of nonspecific symptoms. Provision of close and active follow-up is important in the prodromal phase. Treatment of first-episode psychosis is individual. Usually it involves medication, individual discussions, psychotherapy or music therapy as well as family meetings. The therapy helps the young person become independent. PMID:22312825

  18. Acute pyelonephritis can have serious complications.

    PubMed

    Shields, Joanne; Maxwell, Alexander P

    2010-04-01

    Urinary tract infection (UTI) may predominantly involve the lower urinary tract, i.e. acute cystitis, or upper urinary tract consisting of the renal pelvis and kidney,, i.e. acute pyelonephritis The incidence of acute pyelonephritis is higher in young women than in men but the incidence in men over 65 is similar to that in older women. Women have up to a 10% risk of recurrent acute pyelonephritis in the year following a first acute episode. The equivalent risk in men is 6%. Acute pyelonephritis may be uncomplicated and resolve without serious sequelae. A minority of episodes may be complicated by acute kidney injury, papillary necrosis, renal or perinephric abscess or the development of emphysematous pyelonephritis. Acute pyelonephritis is generally caused by microorganisms ascending from the urethra via the bladder into the upper urinary tract. Rarely the kidney may be seeded by blood-borne infection. Ecoli is the most common uropathogen causing pyelonephritis accounting for 70-90% of infections. Species of Enterococci, Klebsiella, Pseudomonas, Proteus and Staphylococci are responsible for the remaining infections. There is a rising incidence in the community of UTI with bacteria that produce extended spectrum beta-lactamase (ESBL) enzymes. These ESBL bacteria have developed resistance to antibiotics such as penicillin, cephalosporins and increasingly to quinolones. Risk factors for uncomplicated acute pyelonephritis include recent sexual intercourse, acute cystitis, stress incontinence and diabetes and for complicated acute pyelonephritis include pregnancy, diabetes, anatomical abnormalities of the urinary tract and renal calculi. PMID:20486480

  19. Acute recurrent appendicitis with appendicolith.

    PubMed

    Hollerman, J J; Bernstein, M A; Kottamasu, S R; Sirr, S A

    1988-11-01

    Appendiceal disease can be acute, acute recurrent, or chronic. Acute appendicitis is the most common form. Acute recurrent appendicitis is more common than chronic appendicitis. In children the clinical manifestations of appendicitis are variable. Patients who have an appendicolith usually develop appendicitis, often with perforation. A case is presented of 3-year follow-up of a patient with an appendicolith and acute recurrent appendicitis. The literature about appendicoliths is reviewed. In the appropriate clinical setting, a history of prior episodes of similar right lower quadrant pain does not preclude the diagnosis of appendiceal disease. Awareness of the less common forms of appendicitis is important so that appropriate treatment is not delayed. PMID:3052484

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

    PubMed Central

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

    1997-01-01

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

  1. Vagus Nerve Stimulation for Major Depressive Episodes.

    PubMed

    Eljamel, Sam

    2015-01-01

    Stimulation of the left vagus nerve is a novel antidepressive therapy that relies upon the vagal projections to the brain stem to modulate brain circuits involved in mood regulation. There is cumulative evidence from prospective and long-term studies that has demonstrated tolerability and effectiveness of vagus nerve stimulation (VNS) in major depressive episodes (MDE). VNS in MDE has the following advantages: symptomatic response (defined as at least a 50% improvement in MDE severity) occurs in at least 15-17% of patients after 10 weeks of VNS treatment and in at least 22-37% of patients after 12 months of VNS treatment, remissions are observed in at least 15-17% of patients after 12 months of treatment, there is a sustained response in 13-27% of patients during 12 months of VNS, and successful maintenance of the initial improvement is observed in a high percentage of patients (73-77% of patients who had meaningful or greater benefit after 3 months of treatment maintained at least meaningful benefit after 12 months of treatment). VNS is a well-tolerated treatment as indicated by the high continuation rates of VNS therapy in the D01 and D02 studies after 12 months of therapy (90-98%) and the low rate of adverse event-related study discontinuations through 12 months or more in these studies (3%). Adverse effects are characterized by the absence of systemic effects associated with drug therapy and are primarily limited to those related to stimulation of the vagus nerve; many of the common adverse effects only occurred when VNS was on with the ability to stop acute stimulation-related adverse effects immediately through the use of magnet deactivation of the VNS device. More importantly, there were no adverse cognitive and psychomotor effects observed with antidepressant drugs and electroconvulsive therapy, no overdose toxicity observed with antidepressant drugs, favorable findings in animal reproductive studies, and an ability to add VNS therapy to antidepressant drug

  2. Episodic repetitive thought: dimensions, correlates, and consequences.

    PubMed

    Segerstrom, Suzanne C; Stanton, Annette L; Flynn, Sarah McQueary; Roach, Abbey R; Testa, Jamie J; Hardy, Jaime K

    2012-01-01

    Repetitive thought (RT) - attentive, prolonged, or frequent thought about oneself and one's world - plays an important role in many models of psychological and physical ill health (e.g., rumination and worry), as well as models of recovery and well-being (e.g., processing and reminiscing). In these models, repetitive thought is typically treated as stable or trait-like. In contrast, episodic RT reflects what people have "on their minds" at a particular point in time. In four studies, young women (N=94), college students (N=166), first-year law students (N=73), and older adults (N=174) described their episodic RT, which was then rated for qualities including valence, purpose, and theme. Episodic RT valence was associated with mood and depressive symptoms both between (Studies 1-4) and within people (Studies 3-4), and it mediated the effects of dispositional coping through emotional approach (Study 1). The effect of episodic RT valence in turn was moderated by other properties of episodic RT, including purpose, "trait" valence, and theme (Studies 1-4). The study of episodic RT complements that of trait RT and allows for observations of how RT and psychological adjustment change in concert and in context, as well as examining how the RT qualities that are not reflected in trait measures affect adjustment. PMID:21861772

  3. Clinical care management and workflow by episodes.

    PubMed Central

    Claus, P. L.; Carpenter, P. C.; Chute, C. G.; Mohr, D. N.; Gibbons, P. S.

    1997-01-01

    This paper describes the implementation of clinically defined episodes of care and the introduction of an episode-based summary list of patient problems across Mayo Clinic Rochester in 1996 and 1997. Although Mayo's traditional paper-based system has always relied on a type of 'episode of care' (called the "registration") for patient and history management, a new, more clinically relevant definition of episode of care was put into practice in November 1996. This was done to improve care management and operational processes and to provide a basic construct for the electronic medical record. Also since November 1996, a computer-generated summary list of patient problems, the "Master Sheet Summary Report," organized by episode, has been placed in all patient histories. In the third quarter of 1997, the ability to view the episode-based problem summary online was made available to the 3000+ EMR-capable workstations deployed across the Mayo Rochester campus. In addition, the clinically oriented problem summarization process produces an improved basic "package" of clinical information expected to lead to improved analytic decision support, outcomes analysis and epidemiological research. PMID:9357595

  4. Episodic Repetitive Thought: Dimensions, Correlates, and Consequences

    PubMed Central

    Segerstrom, Suzanne C.; Stanton, Annette L.; Flynn, Sarah McQueary; Roach, Abbey R.; Testa, Jamie J.; Hardy, Jaime K.

    2011-01-01

    Repetitive thought (RT) – attentive, prolonged, or frequent thought about oneself and one’s world – plays an important role in many models of psychological and physical ill health (e.g., rumination and worry), as well as models of recovery and well-being (e.g., processing and reminiscing). In these models, repetitive thought is typically treated as stable or trait-like. In contrast, episodic RT reflects what people have “on their minds” at a particular point in time. In four studies, young women (N = 94), college students (N = 166), first-year law students (N = 73), and older adults (N = 174) described their episodic RT, which was then rated for qualities including valence, purpose, and theme. Episodic RT valence was associated with mood and depressive symptoms both between (Studies 1–4) and within people (Studies 3–4), and it mediated the effects of dispositional coping through emotional approach (Study 1). The effect of episodic RT valence in turn was moderated by other properties of episodic RT, including purpose, “trait” valence, and theme (Studies 1–4). The study of episodic RT complements that of trait RT and allows for observations of how RT and psychological adjustment change in concert and in context, as well as examining the RT qualities that are not reflected in trait measures affecting adjustment. PMID:21861772

  5. Rejection of Bromide and Bromate Ions by a Ceramic Membrane

    PubMed Central

    Moslemi, Mohammadreza; Davies, Simon H.; Masten, Susan J.

    2012-01-01

    Abstract Effects of pH and the addition of calcium chloride (CaCl2) on bromate (BrO3−) and bromide (Br−) rejection by a ceramic membrane were investigated. Rejection of both ions increased with pH. At pH 8, the rejection of BrO3− and Br− was 68% and 63%, respectively. Donnan exclusion appears to play an important role in determining rejection of BrO3− and Br−. In the presence of CaCl2, rejection of BrO3− and Br− ions was greatly reduced, confirming the importance of electrostatic interactions in determining rejection of BrO3− and Br−. The effect of Ca2+ is so pronounced that in most natural waters, rejection of both BrO3− and Br− by the membrane would be extremely small. PMID:23236251

  6. Formal thought disorder in first-episode psychosis.

    PubMed

    Ayer, Ahmet; Yalınçetin, Berna; Aydınlı, Esra; Sevilmiş, Şilay; Ulaş, Halis; Binbay, Tolga; Akdede, Berna Binnur; Alptekin, Köksal

    2016-10-01

    Formal thought disorder (FTD) is one of the fundamental symptom clusters of schizophrenia and it was found to be the strongest predictor determining conversion from first-episode acute transient psychotic disorder to schizophrenia. Our goal in the present study was to compare a first-episode psychosis (FEP) sample to a healthy control group in relation to subtypes of FTD. Fifty six patients aged between 15 and 45years with FEP and forty five control subjects were included in the study. All the patients were under medication for less than six weeks or drug-naive. FTD was assessed using the Thought and Language Index (TLI), which is composed of impoverishment of thought and disorganization of thought subscales. FEP patients showed significantly higher scores on the items of poverty of speech, weakening of goal, perseveration, looseness, peculiar word use, peculiar sentence construction and peculiar logic compared to controls. Poverty of speech, perseveration and peculiar word use were the significant factors differentiating FEP patients from controls when controlling for years of education, family history of psychosis and drug abuse. PMID:27565775

  7. 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.

  8. Antibody-Mediated Rejection in Sensitized Nonhuman Primates: Modeling Human Biology.

    PubMed

    Burghuber, C K; Kwun, J; Page, E J; Manook, M; Gibby, A C; Leopardi, F V; Song, M; Farris, A B; Hong, J J; Villinger, F; Adams, A B; Iwakoshi, N N; Knechtle, S J

    2016-06-01

    We have established a model of sensitization in nonhuman primates and tested two immunosuppressive regimens. Animals underwent fully mismatched skin transplantation, and donor-specific antibody (DSA) response was monitored by flow cross-match. Sensitized animals subsequently underwent kidney transplantation from their skin donor. Immunosuppression included tacrolimus, mycophenolate, and methylprednisolone. Three animals received basiliximab induction; compared with nonsensitized animals, they showed a shorter mean survival time (4.7 ± 3.1 vs. 187 ± 88 days). Six animals were treated with T cell depletion (anti-CD4/CD8 mAbs), which prolonged survival (mean survival time 21.6 ± 19.0 days). All presensitized animals showed antibody-mediated rejection (AMR). In two of three basiliximab-injected animals, cellular rejection (ACR) was prominent. After T cell depletion, three of six monkeys experienced early acute rejection within 8 days with histological evidence of thrombotic microangiopathy and AMR. The remaining three monkeys survived 27-44 days, with mixed AMR and ACR. Most T cell-depleted animals experienced a rebound of DSA that correlated with deteriorating kidney function. We also found an increase in proliferating memory B cells (CD20(+) CD27(+) IgD(-) Ki67(+) ), lymph node follicular helper T cells (ICOS(+) PD-1(hi) CXCR5(+) CD4(+) ), and germinal center (GC) response. Depletion controlled cell-mediated rejection in sensitized nonhuman primates better than basiliximab, yet grafts were rejected with concomitant DSA rise. This model provides an opportunity to test novel desensitization strategies. PMID:26705099

  9. Oedipal shame, rejection, and adolescent development.

    PubMed

    Caparrotta, Luigi

    2003-12-01

    The definition of oedipal shame, dramatized in Sophocles' tragedy, is the painful affect resulting from accepting the reality of one's origins. A clinical example focusing on shame arising from adoption links oedipal shame to the theme of rejection. Furthermore, in adolescence the revival of the oedipal conflict may reactivate oedipal shame in which unconscious idealized fantasies of personal perfection and the object carried over from childhood have to be renegotiated. This process, illustrated by two clinical vignettes, may reveal entrenched masochistic defenses. An examination of a final scene from a film underscores the significance of oedipal shame in clinical practice. PMID:14703298

  10. 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

  11. Confidence and rejection in automatic speech recognition

    NASA Astrophysics Data System (ADS)

    Colton, Larry Don

    Automatic speech recognition (ASR) is performed imperfectly by computers. For some designated part (e.g., word or phrase) of the ASR output, rejection is deciding (yes or no) whether it is correct, and confidence is the probability (0.0 to 1.0) of it being correct. This thesis presents new methods of rejecting errors and estimating confidence for telephone speech. These are also called word or utterance verification and can be used in wordspotting or voice-response systems. Open-set or out-of-vocabulary situations are a primary focus. Language models are not considered. In vocabulary-dependent rejection all words in the target vocabulary are known in advance and a strategy can be developed for confirming each word. A word-specific artificial neural network (ANN) is shown to discriminate well, and scores from such ANNs are shown on a closed-set recognition task to reorder the N-best hypothesis list (N=3) for improved recognition performance. Segment-based duration and perceptual linear prediction (PLP) features are shown to perform well for such ANNs. The majority of the thesis concerns vocabulary- and task-independent confidence and rejection based on phonetic word models. These can be computed for words even when no training examples of those words have been seen. New techniques are developed using phoneme ranks instead of probabilities in each frame. These are shown to perform as well as the best other methods examined despite the data reduction involved. Certain new weighted averaging schemes are studied but found to give no performance benefit. Hierarchical averaging is shown to improve performance significantly: frame scores combine to make segment (phoneme state) scores, which combine to make phoneme scores, which combine to make word scores. Use of intermediate syllable scores is shown to not affect performance. Normalizing frame scores by an average of the top probabilities in each frame is shown to improve performance significantly. Perplexity of the wrong

  12. Pharmacologic Treatment of First-Episode Schizophrenia: A Review of the Literature

    PubMed Central

    Nandhra, Harpal Sing; Singh, Swaran P.

    2012-01-01

    Objective: To review the evidence base for the efficacy and tolerability of antipsychotic medication for the treatment of the first episode of schizophrenia. Data Source: MEDLINE databases were searched for published articles in English over the last 25 years, from January 1986 to January 2011, on choice of antipsychotic treatment for the first episode of schizophrenia, with an emphasis on efficacy and tolerability of antipsychotic drugs in the acute phase of psychotic illness. Study Selection: The keywords antipsychotic drugs and schizophrenia were used in combination with drug treatment, pharmacologic treatment, efficacy, and tolerability in addition to atypical antipsychotics, first-generation antipsychotics, second-generation antipsychotics, first-episode psychosis, and acute psychotic episode. Data Synthesis: At present, there is no convincing evidence to guide clinicians in choosing a single first-line antipsychotic that is effective in treating the positive and negative symptoms of the first episode of schizophrenia. Even though second-generation antipsychotic drugs offer potential benefits in terms of less extrapyramidal side effects and some benefits in treating negative, affective, and cognitive symptoms, these drugs are not without their own side effects. Conclusions: With the introduction of a number of second-generation antipsychotic drugs there have been significant advances in antipsychotic drug treatment over the last decade. Despite these advances, there are still a number of limitations in continued use of some antipsychotic medications due to their efficacy and tolerability issues in the acute and early maintenance phases of psychosis. Active research in this area would provide more promising results of improved efficacy and tolerability of antipsychotic medication. PMID:22690369

  13. Concealed semantic and episodic autobiographical memory electrified

    PubMed Central

    Ganis, Giorgio; Schendan, Haline E.

    2013-01-01

    Electrophysiology-based concealed information tests (CIT) try to determine whether somebody possesses concealed information about a crime-related item (probe) by comparing event-related potentials (ERPs) between this item and comparison items (irrelevants). Although the broader field is sometimes referred to as “memory detection,” little attention has been paid to the precise type of underlying memory involved. This study begins addressing this issue by examining the key distinction between semantic and episodic memory in the autobiographical domain within a CIT paradigm. This study also addresses the issue of whether multiple repetitions of the items over the course of the session habituate the brain responses. Participants were tested in a 3-stimulus CIT with semantic autobiographical probes (their own date of birth) and episodic autobiographical probes (a secret date learned just before the study). Results dissociated these two memory conditions on several ERP components. Semantic probes elicited a smaller frontal N2 than episodic probes, consistent with the idea that the frontal N2 decreases with greater pre-existing knowledge about the item. Likewise, semantic probes elicited a smaller central N400 than episodic probes. Semantic probes also elicited a larger P3b than episodic probes because of their richer meaning. In contrast, episodic probes elicited a larger late positive complex (LPC) than semantic probes, because of the recent episodic memory associated with them. All these ERPs showed a difference between probes and irrelevants in both memory conditions, except for the N400, which showed a difference only in the semantic condition. Finally, although repetition affected the ERPs, it did not reduce the difference between probes and irrelevants. These findings show that the type of memory associated with a probe has both theoretical and practical importance for CIT research. PMID:23355816

  14. Eosinophilic density in graft biopsies positive for rejection and blood eosinophil count can predict development of post-transplant digestive tract eosinophilia.

    PubMed

    Bush, Jonathan W; Mohammad, Saeed; Melin-Aldana, Hector; Kagalwalla, Amir F; Arva, Nicoleta C

    2016-06-01

    EGID is a known post-transplant complication. Its etiology has been related to antirejection medication, but other factors may also play a role as only few transplant recipients develop EGID despite standardized treatment. This study aimed to determine whether EGID is associated with rejection events and with a specific phenotype of the rejection-positive graft biopsies in children with solid organ transplant. All patients with liver, heart, and kidney transplant followed at our institution were included in the study. Digestive tract eosinophilia was more common in heart and liver recipients and was a rare event after renal transplantation. Subjects with EGID had higher incidence of rejection and elevated peripheral blood AEC. The first rejection event and high AEC values preceded EGID diagnosis in the majority of patients. Histologically, the initial rejection-positive graft biopsy revealed accentuated eosinophilia in EGID patients compared with non-EGID cohort, which correlated with higher blood eosinophil counts at the time of first rejection episode. Prominent graft tissue and peripheral blood eosinophilia prior to EGID diagnosis suggests a predisposition for eosinophil activation in patients with post-transplant digestive eosinophilic disorder. These parameters can be used as markers for subsequent development of EGID. PMID:26917244

  15. Phosphorylated S6 Kinase and S6 Ribosomal Protein are Diagnostic Markers of Antibody Mediated Rejection in Heart Allografts

    PubMed Central

    Valenzuela, Nicole M.; Lai, Chi; Zhang, Qiuheng; Gjertson, David; Fishbein, Michael C; Kobashigawa, Jon A; Deng, Mario; Reed, Elaine F.

    2014-01-01

    Background Anti-MHC class I alloantibodies have been implicated in the processes of acute and chronic rejection. These antibodies (Ab) bind to endothelial cells (EC) and transduce signals leading to the activation of cell survival and proliferation pathways, including Src, FAK, mTOR, and downstream targets ERK, S6 kinase (S6K) and S6 ribosomal protein (S6RP). We tested the hypothesis that phosphorylation of S6K, S6RP and ERK in capillary endothelium may serve as an adjunct diagnostic tool for antibody mediated rejection (AMR) in heart allografts. Methods Diagnosis of AMR was based on histology or immunoperoxidase staining of paraffin-embedded tissue consistent with 2013 ISHLT criteria. Diagnosis of acute cellular rejection (ACR) was based on ISHLT criteria. Endomyocardial biopsies from 67 heart transplant recipients diagnosed with acute rejection [33 with pAMR, 18 with ACR (15 with grade 1R, 3 with grade >2R), 16 with pAMR+ACR (13 with 1R and 3 with >2R)] and 40 age- and gender-matched recipients without rejection were tested for the presence of phosphorylated forms of ERK, S6RP and S6K by immunohistochemistry. Results Immunostaining of endomyocardial biopsies with evidence of pAMR showed significant increase in expression of p-S6K and p-S6RP in capillary EC compared to controls. A weaker association was observed between pAMR and p-ERK. Conclusions Biopsies diagnosed with pAMR often showed phosphorylation of S6K and S6RP, indicating that staining for p-S6K and p-S6RP is useful for the diagnosis of AMR. Our findings support a role for antibody-mediated HLA signaling in the process of graft injury. PMID:25511749

  16. 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. PMID:20882904

  17. 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…

  18. Acute Bronchitis

    MedlinePlus

    ... or though physical contact (for example, on unwashed hands). Being exposed to tobacco smoke, air pollution, dusts, vapors, and fumes can also cause acute bronchitis. Less often, bacteria can also cause acute bronchitis. To diagnose acute ...

  19. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  20. Correlates of Homeless Episodes among Indigenous People

    PubMed Central

    Whitbeck, Les B.; Crawford, Devan M.; Hartshorn, Kelley J. Sittner

    2011-01-01

    This study reports the correlates of homeless episodes among 873 Indigenous adults who are part of an ongoing longitudinal study on four reservations in the Northern Midwest and four Canadian First Nation reserves. Descriptive analyses depict differences between those who have and have not experienced an episode of homelessness in their lifetimes. Multivariate analyses assess factors associated with a history of homeless episodes at the time of their first interview. Results show that individuals with a history of homeless episodes had significantly more individual and family health, mental health, and substance abuse problems. Periods of homelessness also were associated with financial problems. Among the female caretakers who experienced episodes of homelessness over the course of the study, the majority had been homeless at least once prior to the start of the study and approximately one–fifth met criteria for lifetime alcohol dependence, drug abuse, or major depression. Family adversity during childhood was also common for women experiencing homelessness during the study. PMID:21656303

  1. The Prevalence and Diagnostic Validity of Short-Duration Hypomanic Episodes and Major Depressive Episodes.

    PubMed

    Miller, Shefali; Dennehy, Ellen B; Suppes, Trisha

    2016-03-01

    Current diagnostic criteria for a hypomanic episode, as outlined in both the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and DSM-5), require a minimum duration of four consecutive days of symptoms of mood elevation. The 4-day criterion for duration of hypomania has been challenged as arbitrary and lacking empirical support, with many arguing that shorter-duration hypomanic episodes are highly prevalent and that those experiencing these episodes are clinically more similar to patients with bipolar disorder than to those with unipolar major depressive disorder. We review the current evidence regarding the prevalence, diagnostic validity, and longitudinal illness correlates of shorter-duration hypomanic episodes and summarize the arguments for and against broadening the diagnostic criteria for hypomania to include shorter-duration variants. Accumulating findings suggest that patients with major depressive episodes and shorter-duration hypomanic episodes represent a complex clinical phenotype, perhaps best conceptualized as being on the continuum between those with unipolar depressive episodes alone and those with DSM-5-defined bipolar II disorder. Further investigation is warranted, ideally involving large prospective, controlled studies, to elucidate the diagnostic and treatment implications of depression with shorter-duration hypomanic episodes. PMID:26830885

  2. Episodic Memory and Episodic Foresight in 3- and 5-Year-Old Children

    ERIC Educational Resources Information Center

    Hayne, Harlene; Gross, Julien; McNamee, Stephanie; Fitzgibbon, Olivia; Tustin, Karen

    2011-01-01

    In the present study, we examined the development of episodic memory and episodic foresight. Three- and 5-year-olds were interviewed individually using a personalised timeline that included photographs of them at different points in their life. After constructing the timeline with the experimenter, each child was asked to discuss a number of…

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

    PubMed

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

    2011-01-01

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

  4. Rejection Sensitivity in Late Adolescence: Social and Emotional Sequelae

    PubMed Central

    Marston, Emily G.; Hare, Amanda; Allen, Joseph P.

    2010-01-01

    This study used longitudinal, multi-reporter data, in a community sample, to examine the role of rejection sensitivity in late adolescents’ social and emotional development. Rejection sensitivity was linked to a relative increase in adolescent depressive and anxiety symptoms over a three-year period, even after accounting for teens’ baseline level of social competence. Additionally, reciprocal relationships emerged between rejection sensitivity and internalizing symptoms. Rejection sensitivity was also linked to relative decreases in peer-reports of teens’ social competence over a three-year period. Consistent with research on gendered socialization, males reported higher levels of rejection sensitivity than females at age 16 and 17. Results are interpreted as highlighting the importance of rejection sensitivity in understanding late adolescent social and emotional development. PMID:21113326

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

    SciTech Connect

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

    1991-03-01

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

  6. The Rejection-Rage Contingency in Borderline Personality Disorder

    PubMed Central

    Berenson, Kathy R.; Downey, Geraldine; Rafaeli, Eshkol; Coifman, Karin; Leventhal, Nina

    2011-01-01

    Though longstanding clinical observation reflected in the DSM-IV suggests that the rage characteristic of borderline personality disorder (BPD) often appears in response to perceived rejection, the role of perceived rejection in triggering rage in BPD has never been empirically tested. Extending basic personality research on rejection sensitivity to a clinical sample, a priming-pronunciation experiment and a 21-day experience-sampling diary examined the contingent relationship between perceived rejection and rage in participants diagnosed with BPD compared to healthy controls. Despite the differences in these two assessment methods, the indices of rejection-contingent rage that they produced were both elevated in the BPD group, and were strongly interrelated. They provide corroborating evidence that reactions to perceived rejection significantly explain the rage seen in BPD. PMID:21500875

  7. 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. PMID:24846784

  8. Timing of spontaneous sleep-paralysis episodes.

    PubMed

    Girard, Todd A; Cheyne, J Allan

    2006-06-01

    The objective of this prospective naturalistic field study was to determine the distribution of naturally occurring sleep-paralysis (SP) episodes over the course of nocturnal sleep and their relation to bedtimes. Regular SP experiencers (N = 348) who had previously filled out a screening assessment for SP as well as a general sleep survey were recruited. Participants reported, online over the World Wide Web, using a standard reporting form, bedtimes and subsequent latencies of spontaneous episodes of SP occurring in their homes shortly after their occurrence. The distribution of SP episodes over nights was skewed to the first 2 h following bedtime. Just over one quarter of SP episodes occurred within 1 h of bedtime, although episodes were reported throughout the night with a minor mode around the time of normal waking. SP latencies following bedtimes were moderately consistent across episodes and independent of bedtimes. Additionally, profiles of SP latencies validated self-reported hypnagogic, hypnomesic, and hypnopompic SP categories, as occurring near the beginning, middle, and end of the night/sleep period respectively. Results are consistent with the hypothesis that SP timing is controlled by mechanisms initiated at or following sleep onset. These results also suggest that SP, rather than uniquely reflecting anomalous sleep-onset rapid eye movement (REM) periods, may result from failure to maintain sleep during REM periods at any point during the sleep period. On this view, SP may sometimes reflect the maintenance of REM consciousness when waking and SP hallucinations the continuation of dream experiences into waking life. PMID:16704578

  9. Evaluation of Risk Factors for Recurrent Wheezing Episodes

    PubMed Central

    Bozaykut, Abdulkadir; Paketci, Ahu; Sezer, Rabia Gonul; Paketci, Cem

    2013-01-01

    Background We aimed to evaluate the risk factors for recurrent wheezing in patients diagnosed with acute bronchiolitis. Method From 2009 to 2011, 500 patients from the pediatric clinics, with first attack of acute bronchiolitis were included in this prospective study. Each patient’s age, gender, birth weight, duration of breastfeeding, family history of atopy and asthma, smoking exposure, source of heating in the house, the presence of pets, any history of chronic disease have been questioned. The patients were followed for a duration of 12 - 24 months. Results In this study, 39% (n = 195) of the cases were female and 61% (n = 305) were male, with a median age of 3 months old. Male gender, low birth weight (< 2,500 g), low gestational age (< 37 weeks), breastfeeding of less than 6 months, congenital heart disease, family history of atopy, asthma, smoking exposure, stove warming, was found as significant risk factors for recurrent wheezing, however, presence of pets at home was found to be a protective factor. Conclusions Informing parents about the risk factors such as exposure to cigarette smoke, heating mode, duration of breastfeeding can significantly decrease recurrent episodes of wheezing. PMID:23976913

  10. Acute Gastric Dilatation in Anorexia Nervosa

    PubMed Central

    Jennings, K. P.; Klidjian, A. M.

    1974-01-01

    Two patients with anorexia nervosa were treated on a general surgical unit for acute gastric dilatation. In both cases the dilatation rapidly followed an increase in the usual low dietary intake of the patients, and the ingestion of extra food may have initiated the acute episode. Conservative treatment with parenteral fluids, nasogastric intubation, and then a gradual return to a normal diet proved a satisfactory method of management. In one patient the anorexia itself was improved. PMID:4834098

  11. Prediction of Acute Respiratory Disease in Current and Former Smokers With and Without COPD

    PubMed Central

    Kim, Victor; Regan, Elizabeth; Williams, André A. A.; Santorico, Stephanie A.; Make, Barry J.; Lynch, David A.; Hokanson, John E.; Washko, George R.; Bercz, Peter; Soler, Xavier; Marchetti, Nathaniel; Criner, Gerard J.; Ramsdell, Joe; Han, MeiLan K.; Demeo, Dawn; Anzueto, Antonio; Comellas, Alejandro; Crapo, James D.; Dransfield, Mark; Wells, J. Michael; Hersh, Craig P.; MacIntyre, Neil; Martinez, Fernando; Nath, Hrudaya P.; Niewoehner, Dennis; Sciurba, Frank; Sharafkhaneh, Amir; Silverman, Edwin K.; van Beek, Edwin J. R.; Wilson, Carla; Wendt, Christine; Wise, Robert A.; Curtis, Jeffrey; Kazerooni, Ella; Hanania, Nicola; Alapat, Philip; Bandi, Venkata; Guntupalli, Kalpalatha; Guy, Elizabeth; Lunn, William; Mallampalli, Antara; Trinh, Charles; Atik, Mustafa; DeMeo, Dawn; Hersh, Craig; Jacobson, Francine; Graham Barr, R.; Thomashow, Byron; Austin, John; MacIntyre, Neil; Washington, Lacey; Page McAdams, H.; Rosiello, Richard; Bresnahan, Timothy; McEvoy, Charlene; Tashjian, Joseph; Wise, Robert; Hansel, Nadia; Brown, Robert; Casaburi, Richard; Porszasz, Janos; Fischer, Hans; Budoff, Matt; Sharafkhaneh, Amir; Niewoehner, Dennis; Allen, Tadashi; Rice, Kathryn; Foreman, Marilyn; Westney, Gloria; Berkowitz, Eugene; Bowler, Russell; Friedlander, Adam; Meoni, Eleonora; Criner, Gerard; Kim, Victor; Marchetti, Nathaniel; Satti, Aditi; James Mamary, A.; Steiner, Robert; Dass, Chandra; Bailey, William; Dransfield, Mark; Gerald, Lynn; Nath, Hrudaya; Ramsdell, Joe; Ferguson, Paul; Friedman, Paul; McLennan, Geoffrey; van Beek, Edwin JR; Martinez, Fernando; Han, MeiLan; Thompson, Deborah; Kazerooni, Ella; Wendt, Christine; Allen, Tadashi; Sciurba, Frank; Weissfeld, Joel; Fuhrman, Carl; Bon, Jessica; Anzueto, Antonio; Adams, Sandra; Orozco, Carlos; Santiago Restrepo, C.; Mumbower, Amy; Crapo, James; Silverman, Edwin; Make, Barry; Regan, Elizabeth; Samet, Jonathan; Willis, Amy; Stinson, Douglas; Beaty, Terri; Klanderman, Barbara; Laird, Nan; Lange, Christoph; Ionita, Iuliana; Santorico, Stephanie; Silverman, Edwin; Lynch, David; Schroeder, Joyce; Newell, John; Reilly, John; Coxson, Harvey; Judy, Philip; Hoffman, Eric; San Jose Estepar, Raul; Washko, George; Leek, Rebecca; Zach, Jordan; Kluiber, Alex; Rodionova, Anastasia; Mann, Tanya; Crapo, Robert; Jensen, Robert; Farzadegan, Homayoon; Murphy, James; Everett, Douglas; Wilson, Carla; Hokanson, John

    2014-01-01

    BACKGROUND: The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS: Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS: At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George’s Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS: Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD. PMID:24945159

  12. Acute small bowel obstruction due to chicken bone bezoar

    PubMed Central

    Vetpillai, Preadeepan; Oshowo, Ayo

    2012-01-01

    Acute intestinal obstruction due to foreign bodies, or bezoar, is a rare occurrence in an adult with a normal intestinal tract. We report an unusual case of a 43-year-old black man with no previous abdominal surgery and no significant medical history who presented with an acute episode of small bowel obstruction due to an impacted undigested chicken bone. PMID:23754931

  13. Automatic detection of regional heart rejection in USPIO-enhanced MRI.

    PubMed

    Chang, Hsun-Hsien; Moura, José M F; Wu, Yijen L; Ho, Chien

    2008-08-01

    Contrast-enhanced magnetic resonance imaging (MRI) is useful to study the infiltration of cells in vivo. This research adopts ultrasmall superparamagnetic iron oxide (USPIO) particles as contrast agents. USPIO particles administered intravenously can be endocytosed by circulating immune cells, in particular, macrophages. Hence, macrophages are labeled with USPIO particles. When a transplanted heart undergoes rejection, immune cells will infiltrate the allograft. Imaged by T(2)(*)-weighted MRI, USPIO-labeled macrophages display dark pixel intensities. Detecting these labeled cells in the image facilitates the identification of acute heart rejection. This paper develops a classifier to detect the presence of USPIO-labeled macrophages in the myocardium in the framework of spectral graph theory. First, we describe a USPIO-enhanced heart image with a graph. Classification becomes equivalent to partitioning the graph into two disjoint subgraphs. We use the Cheeger constant of the graph as an objective functional to derive the classifier. We represent the classifier as a linear combination of basis functions given from the spectral analysis of the graph Laplacian. Minimization of the Cheeger constant based functional leads to the optimal classifier. Experimental results and comparisons with other methods suggest the feasibility of our approach to study the rejection of hearts imaged by USPIO-enhanced MRI. PMID:18672427

  14. Automatic Detection of Regional Heart Rejection in USPIO-Enhanced MRI

    PubMed Central

    Chang, Hsun-Hsien; Moura, José M. F.; Wu, Yijen L.; Ho, Chien

    2008-01-01

    Contrast-enhanced magnetic resonance imaging (MRI) is useful to study the infiltration of cells in vivo. This research adopts ultrasmall superparamagnetic iron oxide (USPIO) particles as contrast agents. USPIO particles administered intravenously can be endocytosed by circulating immune cells, in particular, macrophages. Hence, macrophages are labeled with USPIO particles. When a transplanted heart undergoes rejection, immune cells will infiltrate the allograft. Imaged by T2∗- weighted MRI, USPIO-labeled macrophages display dark pixel intensities. Detecting these labeled cells in the image facilitates the identification of acute heart rejection. This paper develops a classifier to detect the presence of USPIO-labeled macrophages in the myocardium in the framework of spectral graph theory. First, we describe a USPIO-enhanced heart image with a graph. Classification becomes equivalent to partitioning the graph into two disjoint subgraphs. We use the Cheeger constant of the graph as an objective functional to derive the classifier. We represent the classifier as a linear combination of basis functions given from the spectral analysis of the graph Laplacian. Minimization of the Cheeger constant based functional leads to the optimal classifier. Experimental results and comparisons with other methods suggest the feasibility of our approach to study the rejection of hearts imaged by USPIO-enhanced MRI. PMID:18672427

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. Spanish for Agricultural Purposes: The Video Episodes.

    ERIC Educational Resources Information Center

    Mainous, Bruce H.; And Others

    The transcripts of dialogues from videotape recordings were developed, along with accompanying language laboratory material, as part of a one-semester course in Spanish for North American agriculture specialists preparing to work in Latin America. Included are 48 episodes covering such topics as: working with a local Spanish-speaking counterpart,…

  18. Autobiographical Thinking Interferes with Episodic Memory Consolidation

    PubMed Central

    Craig, Michael; Della Sala, Sergio; Dewar, Michaela

    2014-01-01

    New episodic memories are retained better if learning is followed by a few minutes of wakeful rest than by the encoding of novel external information. Novel encoding is said to interfere with the consolidation of recently acquired episodic memories. Here we report four experiments in which we examined whether autobiographical thinking, i.e. an ‘internal’ memory activity, also interferes with episodic memory consolidation. Participants were presented with three wordlists consisting of common nouns; one list was followed by wakeful rest, one by novel picture encoding and one by autobiographical retrieval/future imagination, cued by concrete sounds. Both novel encoding and autobiographical retrieval/future imagination lowered wordlist retention significantly. Follow-up experiments demonstrated that the interference by our cued autobiographical retrieval/future imagination delay condition could not be accounted for by the sound cues alone or by executive retrieval processes. Moreover, our results demonstrated evidence of a temporal gradient of interference across experiments. Thus, we propose that rich autobiographical retrieval/future imagination hampers the consolidation of recently acquired episodic memories and that such interference is particularly likely in the presence of external concrete cues. PMID:24736665

  19. Effects of Episodic Crowding: A Developmental Perspective.

    ERIC Educational Resources Information Center

    Aiello, John R.

    The social, behavioral, and physiological effects of episodic crowding on children and elderly adults are reported in this paper. Children ranging in ages from 9 to 16 and elderly adults ranging in ages from 60 to 90 were grouped by age into small and large rooms. Each group sat silently for 30 minutes in the rooms while skin conductance equipment…

  20. Episodic Accretion among the Orion Protostars

    NASA Astrophysics Data System (ADS)

    Fischer, William J.; Safron, Emily; Megeath, S. Thomas

    2016-06-01

    Episodic accretion, where a young stellar object undergoes stochastic spikes in its disk-to-star accretion rate one or more times over its formation period, may be a crucial process in the formation of low-mass stars. These spikes result in a factor of 10 to 100 increase in the source luminosity over the course of several months that may persist for years. Six years after the Spitzer survey of the Orion molecular clouds, the WISE telescope mapped Orion with similar wavelength coverage. Thus, the two surveys can be used to explore the mid-infrared variability of young stars on this timescale, which is suitable for discovering episodic accretion events. Out of 319 Orion protostars that were targets of the Herschel Orion Protostar Survey, we identified two examples of episodic accretion with this method. One of them, HOPS 223, was previously known. The other, HOPS 383, is the first known example of episodic accretion in a Class 0 protostar (age < 0.2 Myr). With these and one other outburst that began early in the Spitzer mission, we estimate that the most likely interval between protostellar outbursts is 740 years, with a 90% confidence interval of 470 to 6200 years. These outbursts are weaker than the optically revealed FU Ori events. We will update the mid-infrared light curves of HOPS 223 and HOPS 383 with recent data from FORCAST aboard SOFIA; HOPS 223 shows signs of fading.