Sample records for posttransplant lymphoproliferative disease

  1. Posttransplant Lymphoproliferative Disease in Liver Transplant Patients

    Microsoft Academic Search

    Christina Hartmann; Marcus Schuchmann; Tim Zimmermann

    2011-01-01

    Posttransplant lymphoproliferative disorders (PTLD) are a life-threatening complication following solid organ transplantation.\\u000a Many posttransplant lymphomas develop from the uncontrolled proliferation of Epstein–Barr virus (EBV)-infected B-cells, whereas\\u000a EBV-negative PTLDs were increasingly recognized within the past decade. Major risk factors for the development of PTLDs after\\u000a liver transplantation are immunosuppressive therapy and the type of underlying disease: viral hepatitis, autoimmune liver\\u000a disease,

  2. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease.

    PubMed

    Kim, Manbok; Rahman, Masmudur M; Cogle, Christopher R; McFadden, Grant

    2015-07-10

    Epstein-Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. PMID:25843801

  3. Complete immunosuppressive withdrawal as a uniform approach to post-transplant lymphoproliferative disease in pediatric liver transplantation.

    PubMed

    Hurwitz, Melissa; Desai, Dev M; Cox, Kenneth L; Berquist, William E; Esquivel, Carlos O; Millan, Maria T

    2004-06-01

    Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients is associated with a high mortality (up to 60%) and the younger age groups, who are predominantly EBV-naďve, are at highest risk for development of this disease. The aim of this study is to assess, in this high-risk group, patient outcome and graft loss to rejection when complete withdrawal of immunosuppressive agents (IMS) is instituted as the mainstay of treatment in addition to the use of standard therapy. A retrospective analysis of 335 pediatric patients whose liver transplants were performed by our team between September 1988 and September 2002, was carried out through review of computer records, database and patient charts. Fifty patients developed either EBV or PTLD; 80% were < or =2 yr of age. Of these 50 patients, 19 had a positive tissue diagnosis for PTLD and 31 were diagnosed with EBV infection, 14 of whom had positive tissue for EBV. Fifty-eight percent of patients who developed PTLD and 51.6% of patients with EBV received antibody for induction or treatment of rejection prior to onset of disease. Forty-six patients (92%) received post-transplant antiviral prophylaxis with ganciclovir or acyclovir. Antiviral treatment included ganciclovir in 76%, acyclovir in 20% and Cytogam (in addition to one of the former agents) in 44%. In those with PTLD, treatment included chemotherapy (n = 1), Rituximab (n = 2), and ocular radiation (n = 1). IMS was stopped in all patients with PTLD and in 19 with EBV infection and was held as long as there was no allograft rejection. Eight patients have remained off IMS for a mean of 1535.5 +/- 623 days. Of the 21 patients who were restarted on IMS for acute rejection, 18 responded to steroids and/or reinstitution of low-dose calcineurin inhibitors. The mean time to rejection while off IMS in this group was 107.43 +/- 140 days (range: 7-476). Two patients were re-transplanted for chronic rejection; one had chronic rejection that existed prior to discontinuing IMS. The mortality rate in our series was 31.6% in those with PTLD and 6% in those with EBV disease. The cause of death was related to PTLD or sepsis in all cases; no deaths were due to graft loss from acute or chronic rejection. PTLD is associated with high mortality in the pediatric population. Based on this report, we advocate aggressive management of PTLD that is composed of early cessation of IMS, the use of antiviral therapy, and chemotherapy when indicated. Episodes of rejection that occur after stopping IMS can be successfully treated with standard therapy without graft loss to acute rejection. PMID:15176965

  4. Pediatric post-transplant lymphoproliferative disorder after cardiac transplantation

    Microsoft Academic Search

    Hideaki Ohta; Norihide Fukushima; Keiichi Ozono

    2009-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a well recognized and potentially fatal complication after pediatric\\u000a cardiac transplantation. PTLD encompasses a wide spectrum, ranging from benign hyperplasia to more aggressive lymphoma. Most\\u000a cases are Epstein-Barr virus (EBV)-related B-cell tumors resulting from impaired immunity due to immunosuppressive therapy.\\u000a Pediatric recipients, often seronegative for EBV at transplantation, have a greater risk for PTLD than

  5. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation

    Microsoft Academic Search

    Anna L. Taylor; Robert Marcus; J. Andrew Bradley

    2005-01-01

    Post-transplant lymphoproliferative disorders (PTLD) are a well-recognised and potentially fatal complication after solid organ transplantation. They include a spectrum of disorders ranging from benign hyperplasia to invasive malignant lymphoma. The majority of cases are associated with Epstein Barr virus (EBV)-driven tumour formation in B cells and are a consequence of the detrimental effect of immunosuppressive agents on the immune-control of

  6. Isolated Upper Extremity Posttransplant Lymphoproliferative Disorder in a Child

    PubMed Central

    Halula, Sarah E.; Leino, Daniel G.; Patel, Manish N.; Racadio, John M.; Lungren, Matthew P.

    2015-01-01

    Posttransplant lymphoproliferative disorder (PTLD) is a well-described complication of solid organ and bone marrow transplants. The most common presentation is intra-abdominal lymphadenopathy or single or multiple intraparenchymal masses involving the liver, spleen, or kidneys. Here we describe the imaging and pathology findings of an unusual case of PTLD appearing as an intramuscular forearm lesion in a pediatric male. The manifestation of PTLD as an isolated upper extremity mass in a pediatric patient has to our knowledge not been described. PMID:26167324

  7. Activation and Adoptive Transfer of Epstein-Barr Virus-Specific Cytotoxic T Cells in Solid Organ Transplant Patients with Posttransplant Lymphoproliferative Disease

    Microsoft Academic Search

    Rajiv Khanna; Scott Bell; Martina Sherriti; Andrew Galbraith; Scott R. Burrows; Lee Rafter; Belinda Clarke; Richard Slaughter; Michael C. Falk; Jo Douglass; Trevor Williams; Suzanne L. Ellioti; Denis J. Moss

    1999-01-01

    The treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential

  8. Post-transplant lymphoproliferative disease of donor origin, following haematopoietic stem cell transplantation in a patient with blastic plasmacytoid dendritic cell neoplasm.

    PubMed

    Piccin, Andrea; Morello, Enrico; Svaldi, Mirija; Haferlach, Torsten; Facchetti, Fabio; Negri, Giovanni; Vecchiato, Cinzia; Fisogni, Simona; Pusceddu, Irene; Cortelazzo, Sergio

    2012-12-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare condition that originates from dendritic cells. We report on the first case of Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disorder (PTLD) of donor origin in a BPDC patient post-allogeneic haematopoietic stem cell transplantation (HSCT). Flow cytometry study identified a cell population CD4+/CD56+/CD45RA+/CD123+/TCL1+ suggestive of BPDCN diagnosis, which was confirmed by a lymph node biopsy (cells positive for BCL11a, BDCA-2, CD2AP, CD123, TCL1 and S100). Cytogenetic analysis revealed a complex karyotype: (19 metaphase) 47,XX,t(1;6)(q21;q2?5),-13?+?2mar[11]/47, XX, +21 [3]/46,XX [5]. The patient was started on acute myeloid leukaemia (AML) induction schedule, and subsequently an allogeneic HSCT was performed. On day +36 post-HSCT, bone marrow biopsy/aspirate showed complete morphological remission, and chimerism study showed 100% donor chimera. However, on day +37, the patient was found to have enlarged cervical and supraclavicular lymphoadenopathy, splenomegaly and raised lactic dehydrogenase. EBV-DNA copies in blood were elevated, consistent with a lytic cycle. A lymph node biopsy showed EBV encoded RNA and large atypical B cells (CD45dim-, CD4+/CD56+, monoclonal for k-chain, CD19+/CD20+/CD21+/CD22+/CD38+/CD43+/CD79?-/CD5-/CD10-), consistent with PTLD monomorphic type. Chimerism study showed that PTLD was of donor origin. This case together with the recent literature findings on BPDCN and PTLD are discussed. PMID:22915052

  9. Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease.

    PubMed

    Khanna, R; Bell, S; Sherritt, M; Galbraith, A; Burrows, S R; Rafter, L; Clarke, B; Slaughter, R; Falk, M C; Douglass, J; Williams, T; Elliott, S L; Moss, D J

    1999-08-31

    The treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential use for immunotherapy against PTLD in solid organ transplant patients. Peripheral blood mononuclear cells from a panel of solid organ transplant recipients with and without active PTLD were used to assess EBV-specific memory CTL responses. The activation protocol involved cocultivation of peripheral blood mononuclear cells with an autologous lymphoblastoid cell line under conditions that favored expansion of virus-specific CTL and hindered the proliferation of allospecific T cells. These CTL consistently showed (i) strong EBV-specificity, including reactivity through defined epitopes in spite of concurrent immunosuppressive therapy, and (ii) no alloreactivity toward donor alloantigens. More importantly, adoptive transfer of these autologous CTLs into a single patient with active PTLD was coincident with a very significant regression of the PTLD. These results demonstrate that a potent EBV-specific memory response can be expanded from solid organ recipients who have acquired their primary EBV infection under high levels of immunosuppressive therapy and that these T cells may have therapeutic potential against PTLD. PMID:10468618

  10. Lymphoproliferative Disease of the Orbit.

    PubMed

    Li, Emmy Y; Yuen, Hunter K; Cheuk, Wah

    2015-01-01

    Lymphoproliferative diseases of the orbit account for majority of orbital tumors. The pathologies range from reactive lymphoid hyperplasia to specific IgG4-related inflammation to malignant lymphomas. This review summarizes current concepts regarding pathology, clinical presentation, diagnosis, staging, and treatment strategies of major orbital lymphoproliferative diseases based on updated and relevant bibliography. PMID:26065355

  11. Molecular Pathogenesis of B-Cell Posttransplant Lymphoproliferative Disorder: What Do We Know So Far?

    PubMed Central

    Morscio, J.; Dierickx, D.; Tousseyn, T.

    2013-01-01

    Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal disease that arises in 2%–10% of solid organ and hematopoietic stem cell transplants and is most frequently of B-cell origin. This very heterogeneous disorder ranges from benign lymphoproliferations to malignant lymphomas, and despite the clear association with Epstein-Barr Virus (EBV) infection, its etiology is still obscure. Although a number of risk factors have been identified (EBV serostatus, graft type, and immunosuppressive regimen), it is currently not possible to predict which transplant patient will eventually develop PTLD. Genetic studies have linked translocations (involving C-MYC, IGH, BCL-2), various copy number variations, DNA mutations (PIM1, PAX5, C-MYC, RhoH/TTF), and polymorphisms in both the host (IFN-gamma, IL-10, TGF-beta, HLA) and the EBV genome to B-cell PTLD development. Furthermore, the tumor microenvironment seems to play an important role in the course of disease representing a local niche that can allow antitumor immune responses even in an immunocompromised host. Taken together, B-cell PTLD pathogenesis is very complex due to the interplay of many different (patient-dependent) factors and requires thorough molecular analysis for the development of novel tailored therapies. This review aims at giving a global overview of the currently known parameters that contribute to the development of B-cell PTLD. PMID:23690819

  12. Post-transplant lymphoproliferative disorder after kidney transplantation: time to adopt monitoring of Epstein-Barr virus?

    PubMed

    Biller, P; Michaux, L; Pauw, L De; Camboni, A; Mourad, M; Kanaan, N

    2015-06-01

    Although post-transplant lymphoproliferative disorder is a classical complication encountered after kidney transplantation, its diagnosis can still be challenging and its outcome life-threatening. Most cases are related to Epstein-Barr virus (EBV) infection and occur mainly in the first year post-transplant, favoured by the seronegative EBV status of the recipient transplanted with a kidney from a seropositive donor, and strong immunosuppression. We report the case of a young kidney-pancreas transplant recipient who developed post-transplant lymphoproliferative disorder (PTLD) early after transplantation, with a rapid fatal issue. We review the pathogenesis, clinical presentation, and management of PTLD with a focus on prevention. PMID:25541210

  13. Rituximab as Treatment of Posttransplant Lymphoproliferative Disorder in Patients Who Underwent Small Bowel\\/Multivisceral Transplantation: Report of Three Cases

    Microsoft Academic Search

    M. Codeluppi; S. Cocchi; G. Guaraldi; F. Di Benedetto; A. Bagni; M. Pecorari; W. Gennari; A. D. Pinna; G. E. Gerunda; R. Esposito

    2005-01-01

    This report describes three cases of posttransplant lymphoproliferative disorder (PTLD) in multivisceral\\/small bowel transplant patients treated with rituximab (anti-CD20 monoclonal antibodies). In two cases (one of which was a B-cell lymphoma) a good response to therapy was achieved. A third case (with polymorphic PTLD with low CD20 expression) developed a refractory rejection and PTLD was still documented on graftectomy. Rituximab

  14. Hodgkin lymphoma post-transplant lymphoproliferative disorder following pediatric renal transplant: serial imaging with F-18 FDG PET/CT.

    PubMed

    Makis, William; Lisbona, Robert; Derbekyan, Vilma

    2010-09-01

    Post-transplant lymphoproliferative disorder (PTLD) occurs in 1.2% of pediatric renal transplant patients, and is frequently Epstein-Barr Virus mediated. Hodgkin Lymphoma PTLD is the rarest of the 4 types of PTLDs recognized by the World Health Organization, with an incidence of <4% of all PTLD patients. It has a distinct clinical course and treatment from all other types of PTLD. This is a case of a 16-year-old girl who had a renal transplant in 2000 due to Moya Moya disease. Her first F-18 FDG PET/CT done in 2006 showed mildly FDG-avid mediastinal adenopathy (histologically nonspecific reactive nodes), however in 2009, after presenting with fevers, a repeat PET/CT showed extensive intensely FDG-avid disease. Biopsy of a supraclavicular node identified Hodgkin Lymphoma PTLD. The patient was treated with chemotherapy and reimaged, showing excellent response to therapy. In contrast, classic PTLD is treated by withdrawal of immunosuppression and administration of Rituximab. F-18 FDG PET/CT is known to be very useful in the staging and monitoring of response to therapy in the setting of classic PTLD. In this case, serial F-18 FDG PET/CT scans proved very useful in the evaluation and follow-up of the rare and distinct Hodgkin Lymphoma PTLD subtype. PMID:20706047

  15. Maintaining calcineurin inhibition after the diagnosis of post-transplant lymphoproliferative disorder improves renal graft survival.

    PubMed

    Serre, Jean-Emmanuel; Michonneau, David; Bachy, Emmanuel; Noël, Laure-Hélčne; Dubois, Valérie; Suberbielle, Caroline; Kreis, Henri; Legendre, Christophe; Mamzer-Bruneel, Marie-France; Morelon, Emmanuel; Thaunat, Olivier

    2014-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is an uncontrolled proliferation of transformed lymphocytes fostered by immunosuppression. In addition to chemotherapy, treatment of PTLD includes a reduction of maintenance immunosuppression. Patients with PTLD have an increased risk of graft loss, suggesting that reduced immunosuppression strategy needs to be optimized with regard to graft outcome. Here we retrospectively reviewed 101 cases involving PTLD to identify the risks associated with graft loss. During a median follow-up of 70 months, 39 patients died and 21 lost their graft. Multivariate analysis found that an eGFR under 30?ml/min per 1.73?m(2) at PTLD diagnosis, a biopsy-proven acute rejection episode following reduction of immunosuppression, and the absence of calcineurin inhibition in maintenance immunosuppression are independent risk factors for allograft loss. Neither the type of PTLD nor the chemotherapy regimen was predictive of allograft failure. Histological analysis of graft biopsies showed that maintaining calcineurin inhibition after the diagnosis of PTLD reduced the risk of developing de novo anti-HLA antibodies and humoral rejection. Remarkably, calcineurin inhibitor maintenance was neither associated with higher mortality nor with worse progression-free survival. Thus, maintaining calcineurin inhibition at a reduced dose after the diagnosis of PTLD seems safe and may improve renal graft outcome, possibly through better control of the recipient's humoral immune response. PMID:23802193

  16. Occurrence and prognostic relevance of CD30 expression in post-transplant lymphoproliferative disorders.

    PubMed

    Vase, Maja Řlholm; Maksten, Eva Futtrup; Bendix, Knud; Hamilton-Dutoit, Stephen; Andersen, Claus; Mřller, Michael Boe; Sřrensen, Sřren Schwartz; Jespersen, Bente; Kampmann, Jan; Sřndergĺrd, Esben; Nielsen, Patricia Switten; D'amore, Francesco

    2015-06-01

    Post-transplant lymphoproliferative disorders (PTLDs) are potentially fatal, often Epstein-Barr virus (EBV)-driven neoplasias developing in immunocompromised hosts. Initial treatment usually consists of a reduction in immunosuppressive therapy and/or rituximab with or without chemotherapy. However, patients who relapse do poorly, and new treatment options are warranted. With the introduction of the immunoconjugate brentuximab vedotin, the CD30 antigen has become an effectively targetable molecule. Therefore, we investigated the frequency and level of CD30 expression in PTLDs. We identified 108 patients with PTLDs diagnosed during 1994-2011, of whom 62 had adequate paraffin-embedded tissue for tissue microarray construction. Immunohistochemical expression of CD30 was consistently detected in all types of PTLD (overall 85.25%), including the monomorphic subtypes, and was correlated with a more favorable outcome. For diffuse large B-cell lymphoma (DLBCL)-type PTLD this was regardless of EBV status, and remained significant in multivariate analysis. Cell-of-origin had no independent prognostic value in our series of DLBCL PTLD. PMID:25248878

  17. Viral induction and targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders.

    PubMed

    Ouyang, Jing; Juszczynski, Przemyslaw; Rodig, Scott J; Green, Michael R; O'Donnell, Evan; Currie, Treeve; Armant, Myriam; Takeyama, Kunihiko; Monti, Stefano; Rabinovich, Gabriel A; Ritz, Jerome; Kutok, Jeffery L; Shipp, Margaret A

    2011-04-21

    Posttransplant lymphoproliferative disorders (PTLDs) are potentially fatal, EBV-driven B-cell malignancies that develop in immunocompromised solid organ or hematopoietic stem cell recipients. In PTLD, the expression of EBV proteins, including latent membrane protein 1 (LMP1) and LMP2A, viral immune evasion strategies, and impaired host immune surveillance foster the proliferation of EBV-transformed B cells. Current PTLD treatment strategies include reduction of immunosuppression, which increases the risk of graft rejection, anti-CD20 treatment, combination chemotherapy, and administration of EBV-specific cytotoxic T cells. In the present study, we report that EBV-transformed lymphoblastoid B-cell lines (LCLs) and primary PTLDs overexpress galectin-1 (Gal1), a carbohydrate-binding lectin that induces tolerogenic dendritic cells and triggers the selective apoptosis of CD4(+) Th1 and Th17 cells and cytotoxic T cells. In transcriptional reporter assays, LMP2A and LMP1 each increased Gal1-driven luciferase expression, and the combination of LMP2A and LMP1 was additive. In addition, small interfering RNA (siRNA)-mediated depletion of LMP2A decreased Gal1 protein abundance in EBV-transformed LCLs. Gal1 expression in LCLs was dependent on both activating protein 1 (AP-1) and PI3K. A newly developed neutralizing Gal1 mAb selectively inhibited Gal1-mediated apoptosis of EBV-specific CD8(+) T cells. Given the tolerogenic and immunosuppressive function of Gal1, antibody-mediated Gal1 neutralization may represent a novel immunotherapeutic strategy for PTLD and other Gal1-expressing tumors. PMID:21300977

  18. Radioimmunotherapy ((90) Y-Ibritumomab Tiuxetan) for Posttransplant Lymphoproliferative Disorders After Prior Exposure to Rituximab.

    PubMed

    Rossignol, J; Terriou, L; Robu, D; Willekens, C; Hivert, B; Pascal, L; Guieze, R; Trappe, R; Baillet, C; Huglo, D; Morschhauser, F

    2015-07-01

    Posttransplantation lymphoproliferative disorders (PTLDs) are life-threatening complications after solid organ and hematopoietic stem cell transplantation. Only half of CD20-positive PTLDs respond to rituximab monotherapy, and outcomes remain poor for patients with relapsed/refractory disease, especially those who do not qualify for an anthracycline containing regimen due to frailty or comorbidities. Radioimmunotherapy (RIT) might be an option in this particular setting. We report a panel of eight patients with rituximab refractory/relapsed CD20-positive PTLDs including three ineligible for subsequent CHOP-like chemotherapy who received (90) Y-Ibritumomab tiuxetan as a single agent (n?=?7) or combined to chemotherapy (n?=?1). Five out of eight patients were kidney transplant recipients, while 2/8 had a liver transplant and 1/8 had a heart transplant. Patients received a median of two previous therapies. Overall response rate was 62.5%. Importantly, all responders achieved complete response. At a median follow-up of 37 months [5; 84], complete response was ongoing in four patients. Toxicity was predominantly hematological and easily manageable. No graft rejection was noticed concomitantly or following RIT administration despite immunosuppression reduction after diagnosis of PTLDs. This report emphasizes the potential efficiency of salvage RIT for early rituximab refractory PTLDs without any unexpected toxicity. PMID:25868706

  19. Adoptive therapy for EBV-induced cancers: driving success with post-transplant lymphoproliferative disorder to other EBV-derived tumors.

    PubMed

    Smith, Corey; Khanna, Rajiv

    2015-06-01

    Epstein-Barr virus (EBV) infection is associated with a range of human malignancies of lymphocytic and epithelial cell origin. In addition to viral-mediated and genetic oncogenic events that lead to the establishment of EBV-associated malignancies, defects in the immune control of EBV likely play a significant role in promoting the survival of malignant cells. This breakdown in immune surveillance is most evident in immunocompromised transplant patients who are susceptible to the development of post-transplant lymphoproliferative disorders. Observations over the last two decades have shown that reconstitution of EBV-specific cellular immunity via adoptive cell therapy can have a dramatic effect on both preventing and treating post-transplant lymphoproliferative disorders, leading to hope that similar strategies could be effective in preventing more prevalent EBV-associated malignancies. PMID:26065480

  20. Post-transplant lymphoproliferative disorder presenting as a tumor adjacent to the renal allograft: A case report and review of the literature

    PubMed Central

    GAO, CHEN; PENG, LONGKAI; PENG, FENGHUA; TUO, TING; LI, DAIQIANG

    2014-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of solid organ transplantation. The current report presents the case of a 42-year-old male who developed PTLD within the first year following renal transplantation. The disorder manifested as a tumor adjacent to the lower pole of the renal allograft and resulted in urinary obstruction. Durable complete remission was achieved as a result of surgical resection followed by a reduction in immunosuppression and low-dose rituximab-based chemotherapy, indicating that this therapeutic strategy may be safe and effective for the treatment of specific cases of localized and resectable PTLD. PMID:25364435

  1. Lymphoproliferative disease virus in wild turkeys in southeast United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously, retroviral neoplasms reported in wild upland game birds in the United States of America have typically been associated with reticuloendotheliosis virus (REV) infection. The information presented herein described the first reports of lymphoproliferative disease virus (LPDV) infection in ...

  2. Identification of lymphoproliferative disease virus in wild turkeys (Meleagris gallopavo) in the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Viral-associated lymphoproliferative neoplasia in domestic poultry is caused by infection with a herpesvirus (Marek’s disease virus) or three species of retroviruses [Reticuloendotheliosis virus (REV), Avian leukosis/sarcoma virus, lymphoproliferative disease virus (LPDV)]. Previously, retroviral n...

  3. Hepatitis C infection and lymphoproliferative disease: Accidental comorbidities?

    PubMed Central

    Khoury, Tawfik; Chen, Shmuel; Adar, Tomer; Jacob, E Ollech; Mizrahi, Meir

    2014-01-01

    Chronic hepatitis C virus (HCV) infection has been associated with liver cancer and cirrhosis, autoimmune disorders such as thyroiditis and mixed cryoglobulinema, and alterations in immune function and chronic inflammation, both implicated in B cell lymphoproliferative diseases that may progress to non-Hodgkin lymphoma (NHL). HCV bound to B cell surface receptors can induce lymphoproliferation, leading to DNA mutations and/or lower antigen response thresholds. These findings and epidemiological reports suggest an association between HCV infection and NHL. We performed a systematic review of the literature to clarify this potential relationship. We searched the English-language literature utilizing Medline, Embase, Paper First, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews, with search terms broadly defined to capture discussions of HCV and its relationship with NHL and/or lymphoproliferative diseases. References were screened to further identify relevant studies and literature in the basic sciences. A total of 62 reports discussing the relationship between HCV, NHL, and lymphoproliferative diseases were identified. Epidemiological studies suggest that at least a portion of NHL may be etiologically attributable to HCV, particularly in areas with high HCV prevalence. Studies that showed a lack of association between HCV infection and lymphoma may have been influenced by small sample size, short follow-up periods, and database limitations. The association appears strongest with the B-cell lymphomas relative to other lymphoproliferative diseases. Mechanisms by which chronic HCV infection promotes lymphoproliferative disease remains unclear. Lymphomagenesis is a multifactorial process involving genetic, environmental, and infectious factors. HCV most probably have a role in the lymphomagenesis but further study to clarify the association and underlying mechanisms is warranted. PMID:25473174

  4. Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas.

    PubMed

    Caillard, S; Lamy, F X; Quelen, C; Dantal, J; Lebranchu, Y; Lang, P; Velten, M; Moulin, B

    2012-03-01

    A registry of posttransplant lymphoproliferative disorders (PTLD) was set up for the entire population of adult kidney transplant recipients in France. Cases of PTLD were prospectively enrolled between January 1, 1998, and December 31, 2007. Ten-year cumulative incidence was analyzed in patients transplanted after January 1, 1989. PTLD risk factors were analyzed in patients transplanted after January 1, 1998 by Cox analysis. Cumulative incidence was 1% after 5 years, 2.1% after 10 years. Multivariate analysis showed that PTLD was significantly associated with: older age of the recipient 47-60 years and >60 years (vs. 33-46 years, adjusted hazard ratio (AHR) = 1.87, CI = 1.22-2.86 and AHR = 2.80, CI = 1.73-4.55, respectively, p < 0.0001), simultaneous kidney-pancreas transplantation (AHR = 2.52, CI = 1.27-5.01 p = 0.008), year of transplant 1998-1999 and 2000-2001 (vs. 2006-2007, AHR = 3.36, CI = 1.64-6.87 and AHR = 3.08, CI = 1.55-6.15, respectively, p = 0.003), EBV mismatch (HR = 5.31, CI = 3.36-8.39, p < 0.001), 5 or 6 HLA mismatches (vs. 0-4, AHR = 1.54, CI = 1.12-2.12, p = 0.008), and induction therapy (AHR = 1.42, CI = 1-2.02, p = 0.05). Analyses of subgroups of PTLD provided new information about PTLD risk factors for early, late, EBV positive and negative, polymorphic, monomorphic, graft and cerebral lymphomas. This nationwide study highlights the increased risk of PTLD as long as 10 years after transplantation and the role of cofactors in modifying PTLD risk, particularly in specific PTLD subgroups. PMID:22226336

  5. X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease

    PubMed Central

    Booth, Claire; Gilmour, Kimberly C.; Veys, Paul; Gennery, Andrew R.; Slatter, Mary A.; Chapel, Helen; Heath, Paul T.; Steward, Colin G.; Smith, Owen; O'Meara, Anna; Kerrigan, Hilary; Mahlaoui, Nizar; Cavazzana-Calvo, Marina; Fischer, Alain; Moshous, Despina; Blanche, Stephane; Pachlopnick-Schmid, Jana; Latour, Sylvain; de Saint-Basile, Genevieve; Albert, Michael; Notheis, Gundula; Rieber, Nikolaus; Strahm, Brigitte; Ritterbusch, Henrike; Lankester, Arjan; Hartwig, Nico G.; Meyts, Isabelle; Plebani, Alessandro; Soresina, Annarosa; Finocchi, Andrea; Pignata, Claudio; Cirillo, Emilia; Bonanomi, Sonia; Peters, Christina; Kalwak, Krzysztof; Pasic, Srdjan; Sedlacek, Petr; Jazbec, Janez; Kanegane, Hirokazu; Nichols, Kim E.; Hanson, I. Celine; Kapoor, Neena; Haddad, Elie; Cowan, Morton; Choo, Sharon; Smart, Joanne; Arkwright, Peter D.

    2011-01-01

    X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinemia, often triggered by Epstein-Barr virus infection. Historical data published before improved treatment regimens shows very poor outcome. We describe a large cohort of 91 genetically defined XLP1 patients collected from centers worldwide and report characteristics and outcome data for 43 patients receiving hematopoietic stem cell transplant (HSCT) and 48 untransplanted patients. The advent of better treatment strategies for HLH and malignancy has greatly reduced mortality for these patients, but HLH still remains the most severe feature of XLP1. Survival after allogeneic HSCT is 81.4% with good immune reconstitution in the large majority of patients and little evidence of posttransplant lymphoproliferative disease. However, survival falls to 50% in patients with HLH as a feature of disease. Untransplanted patients have an overall survival of 62.5% with the majority on immunoglobulin replacement therapy, but the outcome for those untransplanted after HLH is extremely poor (18.8%). HSCT should be undertaken in all patients with HLH, because outcome without transplant is extremely poor. The outcome of HSCT for other manifestations of XLP1 is very good, and if HSCT is not undertaken immediately, patients must be monitored closely for evidence of disease progression. PMID:20926771

  6. Neutropenia and G-CSF in lymphoproliferative diseases

    PubMed Central

    Ria, Roberto; Reale, Antonia; Moschetta, Michele; Dammacco, Franco; Vacca, Angelo

    2013-01-01

    Background Chemotherapy-induced neutropenia is a major cause of morbidity and mortality. It frequently causes dose reductions or treatment delay, which can be prevented or treated by the administration of granulocyte-colony-stimulating factor (G-CSF). However, a better knowledge of the incidence, day of onset after therapy, and duration of neutropenia is essential to optimize the use of G-CSF. Design and methods Six hundred and ninety-four patients from a single institution, affected by lympho-proliferative diseases, were retrospectively reviewed for the occurrence of grade 4 neutropenia and febrile neutropenia (FN). Duration of neutropenia and time of neutrophil nadir were also retrieved. The diagnoses included non-Hodgkin's lymphoma, Hodgkin's lymphoma, and multiple myeloma. Chemotherapy regimens were obviously different according to the diagnosis, disease stage, and first or subsequent lines of therapy. Results No patient received G-CSF as primary prophylaxis. Median nadir did not significantly differ among patients treated with first or successive lines of therapy. The incidence of grade 4 neutropenia and FN ranged from 0 to 94%, depending on the chemotherapy regimen. Patients receiving a first-line chemotherapy regimen had a significantly lower incidence of febrile grade 4 neutropenia compared to patients treated with a second or subsequent line of therapy. The duration of grade 4 neutropenia was significantly longer in patients given second or subsequent lines. Conclusion The results of this study could be useful to define the nadir onset in the hematologic setting in order to correctly tailor timing and duration of G-CSF prophylaxis and to assess the lowest fully effective dose. PMID:23321273

  7. Detection of Epstein-Barr Virus DNA in Sera from Transplant Recipients with Lymphoproliferative Disorders

    Microsoft Academic Search

    AJIT P. LIMAYE; MEEI-LI HUANG; EDERLYN E. ATIENZA; JAMES M. FERRENBERG; LAWRENCE COREY

    1999-01-01

    Early diagnosis of Epstein-Barr Virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD) is important because many patients respond to reduction in immunosuppression, especially if PTLD is detect- ed at an early stage. Previous studies have found elevated EBV DNA levels in blood from patients with PTLD, but these assays required isolation of cellular blood fractions and quantitation. We evaluated the presence of

  8. Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we ...

  9. CNI withdrawal for post-transplant lymphoproliferative disorders in kidney transplant is an independent risk factor for graft failure and mortality.

    PubMed

    Rabot, Nolwenn; Büchler, Matthias; Foucher, Yohann; Moreau, Anne; Debiais, Celine; Machet, Marie-Christine; Kessler, Michelle; Morelon, Emmanuel; Thierry, Antoine; Legendre, Christophe; Rivalan, Joseph; Kamar, Nassim; Dantal, Jacques

    2014-09-01

    Post-transplantation lymphoproliferative disorders (PTLD) are associated with poor patient and graft survival. The risk of rejection and subsequent graft loss are increased by the reduction of immunosuppression therapy, the cornerstone of PTLD treatment. This multicentre, retrospective, nonrandomized cohort study includes 104 adults who developed PTLD after renal or simultaneous renal/pancreatic transplantation between 1990 and 2007. It examines the effect of calcineurin inhibitor (CNI) withdrawal on long-term graft and patient survival. At 10 years postonset of PTLD, the Kaplan-Meier graft loss rate was 43.9% and graft loss or death with functioning graft was 64.4%. Cox multivariate analysis determined risk factors of graft loss as PTLD stage greater than I-II and CNI withdrawal, and for graft loss and mortality, these remained risk factors along with age over 60 years. Type and location of PTLD, year of diagnosis, and chemotherapy regime were not independent risk factors. Multivariate analysis determined CNI withdrawal as the most important risk factor for graft loss (HR = 3.07, CI 95%: 1.04-9.09; P = 0.04) and death (HR: 4.00, CI 95%: 1.77-9.04; P < 0.001). While long-term stable renal function after definitive CNI withdrawal for PTLD has been reported, this review determined that withdrawal is associated with reduced graft and patient survival. PMID:24964147

  10. Methotrexate-associated Lymphoproliferative Disease with Multiple Pulmonary Nodules in a Patient with Rheumatoid Arthritis.

    PubMed

    Suemori, Koichiro; Hasegawa, Hitoshi; Ishizaki, Jun; Matsumoto, Takuya; Onishi, Sachiko; Sada, Eiji; Sugita, Atsuro; Yasukawa, Masaki

    2015-01-01

    Patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) sometimes develop lymphoproliferative disease (LPD). MTX-associated LPD can affect nodal or extranodal sites, including the gastrointestinal tract, skin, lungs, kidneys and soft tissues, at almost equal frequency. However, it is very rare for MTX-associated LPD to manifest as multiple nodules in the lungs. We herein report the case of a RA patient who developed MTX-associated LPD with multiple pulmonary nodules during a 5-year course of MTX therapy. PMID:26028000

  11. A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease.

    PubMed Central

    Sneller, M C; Straus, S E; Jaffe, E S; Jaffe, J S; Fleisher, T A; Stetler-Stevenson, M; Strober, W

    1992-01-01

    In mice, the two distinct autosomal recessive genes lpr and gld can induce a syndrome characterized by autoantibody formation and the progressive accumulation of an unusual CD4-CD8- T cell population in peripheral lymphoid tissue. This phenotype does not precisely mirror any human disease. In this report we describe two patients with a progressive lymphoproliferative disorder associated with autoimmunity. The peripheral blood and lymph nodes of these patients contained large numbers of an unusual CD4-CD8- T cell population. These CD4-CD8- T cells express surface markers characteristic of mature peripheral blood T cells (CD3, CD2, CD5), express the alpha/beta form of the T cell receptor, and do not express surface markers characteristic of immature thymocytes (CD1) or NK cells (CD16, CD56). Functionally, these cells exhibited deficient proliferation and lymphokine production upon stimulation with mitogenic antibodies to CD3 or CD2. Both proliferation and lymphokine production could be augmented by co-stimulation with an antibody directed at the CD28 determinant. The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gld mice. Images PMID:1386609

  12. Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease.

    PubMed

    Vickers, Mark A; Wilkie, Gwen M; Robinson, Nicolas; Rivera, Nadja; Haque, Tanzina; Crawford, Dorothy H; Barry, Jacqueline; Fraser, Neil; Turner, David M; Robertson, Victoria; Dyer, Phil; Flanagan, Peter; Newlands, Helen R; Campbell, John; Turner, Marc L

    2014-11-01

    Epstein-Barr virus (EBV) is associated with several malignancies, including post-transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establishment and operation of a bank of EBV-specific CTLs derived from 25 blood donors with human leucocyte antigen (HLA) types found at high frequency in European populations. Since licensure, there have been enquiries about 37 patients, who shared a median of three class I and two class II HLA types with these donors. Cells have been infused into ten patients with lymphoproliferative disease, eight of whom achieved complete remission. Neither patient with refractory disease was matched for HLA class II. Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission. Thirteen patients died before any cells could be issued, emphasizing that the bank should be contacted before patients become pre-terminal. Thus, this third party donor-derived EBV-specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes. PMID:25066775

  13. Repeated detection of gas in the portal vein after liver transplantation: A sign of EBV-associated post-transplant lymphoproliferation?

    PubMed

    Wallot, Michael A; Klepper, Jörg; Clapuyt, Philippe; Dirsch, Olaf; Malagó, Max; Reding, Raymond; Otte, Jean Bernard; Sokal, Etienne M

    2002-08-01

    A 1-yr-old child presented with intractable right sided pleural effusion and progressive clinical deterioration 3 weeks after liver transplantation for Alagille Syndrome. He had been treated successfully for severe acute rejection before. Ultrasound and Doppler mode studies repeatedly demonstrated air in the portal vein. Intra-abdominal and intra-thoracic lymphoproliferation was detected, and EBV virus load and serology were suggestive of primary EBV infection. Liver biopsy revealed blast-like infiltrates of B-cells, considered diagnostic for post-transplant lymphoproliferative disease. The disease resolved upon reduction of immunosuppression. We suggest that the detection of portal vein gas in pediatric liver transplant recipients beyond the early post-operative period may be a sign of intra-abdominal post-transplant lymphoproliferative disease. PMID:12234275

  14. BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients

    Microsoft Academic Search

    Rowena D. Faulkner; Charles Craddock; Jennifer L. Byrne; Prem Mahendra; Andrew P. Haynes; Hugh G. Prentice; Michael Potter; Antonio Pagliuca; Aloysius Ho; Stephen Devereux; Grant McQuaker; Ghulam Mufti; John Liu; Nigel H. Russell

    2003-01-01

    We report the outcomes of reduced-inten- sity allogeneic stem cell transplantation us- ing BEAM-alemtuzumab conditioning (carmustine, etoposide, cytosine arabino- side, melphalan, and alemtuzumab 10 mg\\/d on days 5t o1) in 6 United Kingdom transplant centers. Sixty-five pa- tients with lymphoproliferative diseases underwent sibling (n 57) or matched unrelated donor (n 8) transplantation. Sustained donor engraftment occurred in 60 (97%) of

  15. Expression of HSV-1 Receptors in EBV-Associated Lymphoproliferative Disease Determines Susceptibility to Oncolytic HSV

    PubMed Central

    Wang, Pin-Yi; Currier, Mark A; Hansford, Loen; Kaplan, David; Chiocca, E. Antonio; Uchida, Hiroaki; Goins, William F.; Cohen, Justus B.; Glorioso, Joseph C.; van Kuppevelt, Toin H.; Mo, Xiaokui; Cripe, Timothy P

    2012-01-01

    Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disease (LPD) after hematopoietic stem cell or solid organ transplantation remains a life-threatening complication. Expression of the virus-encoded gene product, EBER, has been shown to prevent apoptosis via blockade of PKR activation. Because PKR is a major cellular defense against Herpes simplex virus, and oncolytic HSV-1 (oHSV) mutants have shown promising anti-tumor efficacy in preclinical models, we sought to determine whether EBV-LPD cells are susceptible to infection by oHSVs. We tested three primary EBV-infected lymphocyte cell cultures from neuroblastoma (NB) patients as models of naturally acquired EBV-LPD. NB12 was most susceptible, NB122R was intermediate, and NB88R2 was essentially resistant. Despite EBER expression, PKR was activated by oHSV infection. Susceptibility to oHSV correlated with the expression of the HSV receptor, nectin-1. The resistance of NB88R2 was reversed by exogenous nectin-1 expression, whereas down-regulation of nectin-1 on NB12 decreased viral entry. Xenografts derived from the EBV-LPDs exhibited only mild (NB12) or no (NB88R2) response to oHSV injection, compared with a neuroblastoma cell line that showed a significant response. We conclude that EBV-LPDs are relatively resistant to oHSV virotherapy, in some cases due to low virus receptor expression but also due to intact anti-viral PKR signaling. PMID:23254370

  16. Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.

    PubMed

    Pochon, Cécile; Oger, Emmanuel; Michel, Gérard; Dalle, Jean-Hugues; Salmon, Alexandra; Nelken, Brigitte; Bertrand, Yves; Cavé, Hélčne; Cayuela, Jean-Michel; Grardel, Nathalie; Macintyre, Elizabeth; Margueritte, Genevičve; Méchinaud, Françoise; Rohrlich, Pierre; Paillard, Catherine; Demeocq, François; Schneider, Pascale; Plantaz, Dominique; Poirée, Marilyne; Eliaou, Jean-François; Semana, Gilbert; Drunat, Séverine; Jonveaux, Philippe; Bordigoni, Pierre; Gandemer, Virginie

    2015-04-01

    Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days -30, 30, 90 and 150 post-transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre- or post-transplant MRD status ?10(-3) . Only nine patients received DLI. Pre- and post-transplant MRD status, and the duration of ciclosporin were independently associated with 5-year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre-transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post-transplantation was a valuable prognostic tool to guide therapeutic intervention. PMID:25522886

  17. A Rapid Flow Cytometric Screening Test for X-linked Lymphoproliferative Disease due to XIAP Deficiency

    PubMed Central

    Marsh, Rebecca A.; Villanueva, Joyce; Zhang, Kejian; Snow, Andrew L.; Su, Helen C.; Madden, Lisa; Mody, Rajen; Kitchen, Brenda; Marmer, Dan; Jordan, Michael B.; Risma, Kimberly; Filipovich, Alexandra; Bleesing, Jack J.

    2009-01-01

    Background Deficiency of X-linked Inhibitor of Apoptosis (XIAP), caused by BIRC4 gene mutations, is the second known cause of X-linked Lymphoproliferative Disease (XLP), a rare primary immunodeficiency that often presents with life-threatening hemophagocytic lymphohistiocytosis (HLH). Rapid diagnosis of the known genetic causes of HLH, including XIAP deficiency, facilitates the initiation of life-saving treatment and preparation for allogeneic hematopoietic cell transplantation (HCT). Until now, a rapid screening test for XIAP deficiency has not been available. Methods In order to develop a flow cytometric screening test for XIAP deficiency, we first used lymphoblastic cell lines generated from controls and patients with BIRC4 mutations to identify 2 commercially available antibodies specific for native intracellular XIAP. Next, we used these antibodies to study control whole blood leukocyte XIAP expression. We then studied XIAP expression in leukocytes from patients with XLP due to BIRC4 mutations, maternal carriers, and patients following HCT. Results XIAP was expressed by the majority of all whole blood nucleated cells in normal controls. In contrast, XIAP was absent or decreased in all lymphocyte subsets, monocytes and granulocytes from 4 unrelated patients with XLP due to BIRC4 mutations. Bimodal distribution of XIAP expression was evident in two maternal carriers, with significant skewing towards cells expressing normal XIAP. Bimodal distribution was also observed in a patient following HCT. Conclusions Flow cytometric analysis of intracellular XIAP provides a rapid screening test for XLP due to XIAP deficiency. It also allows carrier detection and can be used to monitor donor versus recipient reconstitution following HCT. PMID:19288545

  18. Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma.

    PubMed

    Randen, Ulla; Trřen, Gunhild; Tierens, Anne; Steen, Chloé; Warsame, Abdirashid; Beiske, Klaus; Tjřnnfjord, Geir E; Berentsen, Sigbjřrn; Delabie, Jan

    2014-03-01

    Primary chronic cold agglutinin disease is a rare hemolytic disease mediated by monoclonal IGHV4-34-encoded cold agglutinins with a predominant specificity for the blood group antigen I. Bone marrow from 54 patients was studied to type the underlying lymphoproliferative disorder better. Bone marrow biopsies showed circumscribed intra-parenchymatous nodules with small monotonous monoclonal B cells in 40/54 patients (median infiltration: 10% of marrow cells) with a CD20(+), IgMs(+), IgDs(+), CD27(+), CD5(-/+), CD11c(-), CD23(-), CD38(-) immunophenotype. Neither plasmacytoid cytological features nor expression of plasma cell differentiation-associated transcription factors MUM1, XBP1 and BLIMP1 were noted in these B cells. However, a limited number of mature monoclonal IgM(+), IgD(-) plasma cells were present outside the lymphoid nodules and were diffusely scattered throughout the marrow. Of interest, the MYD88 L265P mutation, typical of lymphoplasmacytic lymphoma, was not detected (17/17 cases). Somatically mutated monoclonal IGHV4-34 gene rearrangement was demonstrated in eight patients with frozen samples (mean sequence homology 95.4%). However, mutations of BCL6 intron 1 were not demonstrated, except in one patient, suggesting that the lymphoma cells had not matured in the germinal center. In conclusion, cold agglutinin-associated lymphoproliferative disease displays homogeneous histological and immunophenotypic features. The absence of plasmacytoid cells, the presence of plasma cells predominantly outside the nodular lymphoid infiltrates, IGHV4-34 restriction and absence of MYD88 L265P mutation strongly suggest that cold agglutinin-associated lymphoproliferative disease is a distinct entity that is different from lymphoplasmacytic lymphoma. PMID:24143001

  19. The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease

    Microsoft Academic Search

    Michael J. Eck; Cox Terhorst; Pablo Engel

    2003-01-01

    SAP (signalling lymphocytic activation molecule (SLAM)-associated protein) is a T- and natural killer (NK)-cell-specific protein containing a single SH2 domain encoded by a gene that is defective or absent in patients with X-linked lymphoproliferative syndrome (XLP). The SH2 domain of SAP binds with high affinity to the cytoplasmic tail of the haematopoietic cell-surface glycoprotein SLAM and five related receptors. SAP

  20. Successful treatment of lymphoproliferative disease complicating primary immunodeficiency/immunodysregulatory disorders with reduced-intensity allogeneic stem-cell transplantation.

    PubMed

    Cohen, Jonathan M; Sebire, Neil J; Harvey, Julia; Gaspar, H Bobby; Cathy, Cale; Jones, Alison; Rao, Kanchan; Cubitt, David; Amrolia, Persis J; Davies, E Graham; Veys, Paul

    2007-09-15

    Lymphoproliferative disease (LPD) is a recognized complication of primary immunodeficiency (PID) and immunodysregulatory syndromes. Historically, it has a very poor outcome. For patients surviving LPD, myeloablative hematopoietic stem cell transplantation (SCT) was the only cure for the underlying PID, with a high risk of developing posttransplantation complications, including recurrent lymphoproliferative disease. We describe 8 patients with a range of PID and immunodysregulatory syndromes complicated by LPD. After initial treatment of the LPD (including the use of anti-CD20 monoclonal antibody, rituximab, in 6 of the patients), all patients underwent reduced-intensity conditioning (RIC) SCT with prospective monitoring for Epstein-Barr virus (EBV) viremia. After transplantation, 3 patients received rituximab, and 3 patients received prophylactic EBV-specific cytotoxic T-lymphocytes. Only 1 patient developed recurrent LPD posttransplantation, which responded to rituximab. All patients who underwent transplantation survive free of LPD and are cured of their PID at a median follow-up of 4 years (range, 1-7 years). With careful monitoring and pre-emptive therapy, we advocate this RIC SCT approach to patients with PID who have pre-existing EBV-LPD. PMID:17502458

  1. Autoimmune lymphoproliferative syndrome-like disease in patients with LRBA mutation.

    PubMed

    Revel-Vilk, Shoshana; Fischer, Ute; Keller, Bärbel; Nabhani, Schafiq; Gámez-Díaz, Laura; Rensing-Ehl, Anne; Gombert, Michael; Hönscheid, Andrea; Saleh, Hani; Shaag, Avraham; Borkhardt, Arndt; Grimbacher, Bodo; Warnatz, Klaus; Elpeleg, Orly; Stepensky, Polina

    2015-07-01

    Mutations in LPS-responsive and beige-like anchor (LRBA) gene were recently described in patients with combined immunodeficiency, enteropathy and autoimmune cytopenia. Here, we extend the clinical and immunological phenotypic spectrum of LRBA associated disorders by reporting on three patients from two unrelated families who presented with splenomegaly and lymphadenopathy, cytopenia, elevated double negative T cells and raised serum Fas ligand levels resembling autoimmune lymphoproliferative syndrome (ALPS) and one asymptomatic patient. Homozygous loss of function mutations in LRBA were identified by whole exome analysis. Similar to ALPS patients, Fas mediated apoptosis was impaired in LRBA deficient patients, while apoptosis in response to stimuli of the intrinsic mitochondria mediated apoptotic pathway was even enhanced. This manuscript illustrates the phenotypic overlap of other primary immunodeficiencies with ALPS-like disorders and strongly underlines the necessity of genetic diagnosis in order to provide early correct diagnosis and subsequent care. PMID:25931386

  2. Cyclosporine A drives a Th17- and Th2-mediated posttransplant obliterative airway disease.

    PubMed

    Lemaître, P H; Vokaer, B; Charbonnier, L-M; Iwakura, Y; Field, K A; Estenne, M; Goldman, M; Leo, O; Remmelink, M; Le Moine, A

    2013-03-01

    Calcineurin-inhibitor refractory bronchiolitis obliterans (BO) represents the leading cause of late graft failure after lung transplantation. T helper (Th)2 and Th17 lymphocytes have been associated with BO development. Taking advantage of a fully allogeneic trachea transplantation model in mice, we addressed the pathogenicity of Th cells in obliterative airway disease (OAD) occurring in cyclosporine A (CsA)-treated recipients. We found that CsA prevented CD8(+) T cell infiltration into the graft and downregulated the Th1 response but affected neither Th2 nor Th17 responses in vivo. In secondary mixed lymphocyte cultures, CsA dramatically decreased donor-specific IFN-? production, enhanced IL-17 production and did not affect IL-13. As CD4(+) depletion efficiently prevented OAD in CsA-treated recipients, we further explored the role of Th2 and Th17 immunity in vivo. Although IL-4 and IL-17 deficient untreated mice developed an OAD comparable to wild-type recipients, a single cytokine deficiency afforded significant protection in CsA-treated recipients. In conclusion, CsA treatment unbalances T helper alloreactivity and favors Th2 and Th17 as coexisting pathways mediating chronic rejection of heterotopic tracheal allografts. PMID:23331973

  3. Blood dendritic cell levels associated with impaired IL-12 production and T-cell deficiency in patients with kidney disease: implications for post-transplant viral infections.

    PubMed

    Chen, Ping; Sun, Qianmei; Huang, Yanfei; Atta, Mohamed G; Turban, Sharon; Segev, Dorry L; Marr, Kieren A; Naqvi, Fizza F; Alachkar, Nada; Kraus, Edward S; Womer, Karl L

    2014-10-01

    Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL-12 production and T-cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV-V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22). Along with a statistically significant reduction in mDC levels, reduced CD8(+) T-cell levels were also demonstrated in the kidney disease groups compared with HC. Reduced PB mDC and monocyte-derived DC (MoDC) IL-12 production was observed after in vitro LPS stimulation in the HD versus HC groups. Finally, ELISpot assays demonstrated less robust CD3(+) INF-? responses by MoDCs pulsed with CMV pp65 peptide from HD patients compared with HC. PB mDC level deficiency in patients with kidney disease is associated with deficient IL-12 production and T-cell level/function, which may explain the known correlation of CD8(+) T-cell lymphopenia with deficient post-transplant antiviral responses. PMID:24963818

  4. Blood dendritic cell levels associated with impaired IL-12 production and T-cell deficiency in patients with kidney disease: implications for post-transplant viral infections

    PubMed Central

    Chen, Ping; Sun, Qianmei; Huang, Yanfei; Atta, Mohamed G.; Turban, Sharon; Segev, Dorry L.; Marr, Kieren A.; Naqvi, Fizza F.; Alachkar, Nada; Kraus, Edward S.; Womer, Karl L.

    2015-01-01

    Summary Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL- 12 production and T-cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV-V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22). Along with a statistically significant reduction in mDC levels, reduced CD8+ T-cell levels were also demonstrated in the kidney disease groups compared with HC. Reduced PB mDC and monocyte-derived DC (MoDC) IL-12 production was observed after in vitro LPS stimulation in the HD versus HC groups. Finally, ELISpot assays demonstrated less robust CD3+ INF-? responses by MoDCs pulsed with CMV pp65 peptide from HD patients compared with HC. PB mDC level deficiency in patients with kidney disease is associated with deficient IL-12 production and T-cell level/function, which may explain the known correlation of CD8+ T-cell lymphopenia with deficient post-transplant antiviral responses. PMID:24963818

  5. Posttransplant bone disease

    Microsoft Academic Search

    Marianne Rix; Ewa Lewin; Klaus Olgaard

    2003-01-01

    Even after a successful kidney transplantation with good kidney function, many renal transplant patients have disabling skeletal symptoms. Approximately 7% to 10% of renal transplant patients may experience a fracture, mainly of the cancellous bones but also of the vertebrae. The fracture frequency is even higher in female renal transplant patients and much higher still in diabetic renal transplant patients.

  6. Missense mutations in SH2D1A identified in patients with X-linked lymphoproliferative disease differentially affect the expression and function of SAP

    Microsoft Academic Search

    Nathan J. Hare; Cindy S. Ma; Frank Alvaro; Kim E. Nichols; Stuart G. Tangye

    2006-01-01

    X-linked lymphoproliferative disease (XLP) is an immunodeficiency resulting from mutations in SH2D1A, which encodes signalling lymphocytic activation molecule (SLAM)-associated protein (SAP). In addition to SLAM, SAP associates with several other cell-surface receptors including 2B4 (CD244), Ly9 (CD229), CD84 and NTB-A. SAP contains a single src-homology-2 domain and acts as an intracellular adaptor protein by recruiting the protein tyrosine kinase FynT

  7. Defective control of Epstein-Barr virus-infected B cell growth in patients with X-linked lymphoproliferative disease.

    PubMed Central

    Yasuda, N; Lai, P K; Rogers, J; Purtlo, D T

    1991-01-01

    We studied the cellular function and lymphokine production of T cells from patients with X-linked lymphoproliferative disease (XLP) when activated by the challenge with Epstein-Barr virus (EBV) infection. We used an assay system in which T cells were stimulated with membrane antigens of autologous EBV-infected B lymphoblastoid cell lines (B-LCL) and we examined cellular and humoral factors derived from the stimulated T cells which control the growth of EBV-infected B-LCL. Immunoglobulin secretion from the autologous B-LCL was suppressed with radiosensitive suppressor cells in the patients with XLP. The degree of suppression was correlated with the immunoglobulin levels in the serum of the patients with acquired hypogammaglobulinaemia (P less than 0.05). In addition, T cells from the patients with XLP failed to produce interferon-gamma (IFN-gamma) (P less than 0.001). Moreover, the T cell supernatants from the patients with XLP were less potent to inhibit the B-LCL growth. This diminished inhibition of the B-LCL growth was correlated well with the decreased concentration of IFN-gamma in the T cell supernatants. These findings suggest that suppressor cells may be activated in the patients with the hypogammaglobulinaemia phenotype of XLP, but the frequent development of B cell lymphoma in hypogammaglobulinaemia indicate that immunoglobulin suppression may not exert enough pressure on the in vivo growth of EBV-infected B cells. The defective secretion of IFN-gamma may be, at least partially, responsible for the abnormal cytotoxic T cell and natural killer activities found in the patients with XLP, and may indicate the clinical evaluation about the preventive injection of IFN-gamma against the development of malignant lymphoma. PMID:1846327

  8. Abundant expression of type l K+ channels. A marker for lymphoproliferative diseases?

    PubMed

    Grissmer, S; Cahalan, M D; Chandy, K G

    1988-08-15

    Using the patch clamp whole-cell recording technique, we studied expression of K+ channels in mAb-defined T cell subsets from diseased C3H-lpr/lpr and C3H-gld/gld mice and from healthy C3H-HeJ congenic controls. Both mutant mouse strains develop a lupus-like syndrome accompanied by hyperplasia of a functionally and phenotypically abnormal T cell subset. These defective cells, which are Thy-1.2+ CD4- CD8- B220+ F23.1+, display an abundance of type l K+ channels. Phenotypically similar lymph node T cells from normal C3H-HeJ mice, or young C3H-lpr/lpr mice before the onset of disease, do not display large numbers of type l K+ channels. CD4+ CD8- T cells (helper/inducer) from the mutant mice express a small number of type n K+ channels, and CD4- CD8+ T cells (suppressor/cytotoxic) show a low level of type l or n' K+ channels, as do their phenotypically equivalent counterparts in the normal mouse thymus. These results suggest that the abundant expression of type l K+ channels is a marker for the defective lpr and gld T cell subset and may reflect the "abnormal" proliferative status of these cells. PMID:2456342

  9. Disclosing the CXCR4 Expression in Lymphoproliferative Diseases by Targeted Molecular Imaging

    PubMed Central

    Wester, Hans Jürgen; Keller, Ulrich; Schottelius, Margret; Beer, Ambros; Philipp-Abbrederis, Kathrin; Hoffmann, Frauke; Šime?ek, Jakub; Gerngross, Carlos; Lassmann, Michael; Herrmann, Ken; Pellegata, Natalia; Rudelius, Martina; Kessler, Horst; Schwaiger, Markus

    2015-01-01

    Chemokine ligand-receptor interactions play a pivotal role in cell attraction and cellular trafficking, both in normal tissue homeostasis and in disease. In cancer, chemokine receptor-4 (CXCR4) expression is an adverse prognostic factor. Early clinical studies suggest that targeting CXCR4 with suitable high-affinity antagonists might be a novel means for therapy. In addition to the preclinical evaluation of [68Ga]Pentixafor in mice bearing human lymphoma xenografts as an exemplary CXCR4-expressing tumor entity, we report on the first clinical applications of [68Ga]Pentixafor-Positron Emission Tomography as a powerful method for CXCR4 imaging in cancer patients. [68Ga]Pentixafor binds with high affinity and selectivity to human CXCR4 and exhibits a favorable dosimetry. [68Ga]Pentixafor-PET provides images with excellent specificity and contrast. This non-invasive imaging technology for quantitative assessment of CXCR4 expression allows to further elucidate the role of CXCR4/CXCL12 ligand interaction in the pathogenesis and treatment of cancer, cardiovascular diseases and autoimmune and inflammatory disorders. PMID:25825601

  10. A Case of Alport Syndrome with Posttransplant Antiglomerular Basement Membrane Disease despite Negative Antiglomerular Basement Membrane Antibodies by EIA Treated with Plasmapheresis and Intravenous Immunoglobulin

    PubMed Central

    Armstead, Sumiko I.; Hellmark, Thomas; Wieslander, Jorgen; Zhou, Xin J.; Rajora, Nilum

    2013-01-01

    Posttransplant antiglomerular basement membrane (anti-GBM) disease occurs in approximately 5% of Alport patients and usually ends in irreversible graft failure. Recent research has focused on characterizing the structure of the anti-GBM alloepitope. Here we present a case of a 22-year-old male with end-stage renal disease secondary to Alport syndrome, with a previously failed renal allograft, who received a second deceased-donor kidney transplant. Six days after transplantation, he developed acute kidney injury. The serum anti-GBM IgG was negative by enzyme immunoassay (EIA). On biopsy, he had crescentic glomerulonephritis with linear GBM fixation of IgG. With further analysis by western blotting, we were able to detect antibodies to an unidentified protein from the basement membrane. This patient was treated with plasmapheresis twice per week and monthly intravenous immunoglobulin (IVIG) for a total of five months. At the end of treatment, these unknown antibodies were no longer detected. His renal function improved, and he has not required dialysis. We conclude that anti-GBM disease in patients with Alport Syndrome may be caused by circulating antibodies to other components of the basement membrane that are undetectable by routine anti-GBM EIA and may respond to treatment with plasmapheresis and IVIG. PMID:24363950

  11. Autoimmune Lymphoproliferative Syndrome (ALPS)

    MedlinePLUS

    ... Syndrome (ALPS) Top Banner Content Area Skip Content Marketing Share this: Main Content Area Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of the immune system that affects both children and adults. In ALPS, unusually high numbers of ...

  12. EXPRESSION OF EPSTEIN–BARR VIRUS–ENCODED SMALL RNA (BY THE EBER-1 GENE) IN LIVER SPECIMENS FROM TRANSPLANT RECIPIENTS WITH POST-TRANSPLANTATION LYMPHOPROLIFERATIVE DISEASE

    PubMed Central

    Randhawa, Parmjeet S.; Jaffe, Ronald; Demetris, Anthony J.; Nalesnik, Michael; Starzl, Thomas E.; Chen, Yuan Yuan; Weiss, Lawrence M.

    2010-01-01

    Background Epstein–Barr virus (EBV)–associated post-transplantation lymphoproliferative disease (PTLD) develops in 1 to 10 percent of transplant recipients, in whom it can be treated by a reduction in the level of immunosuppression. We postulated that the tissue expression of the small RNA transcribed by the EBER-1 gene during latent EBV infection would identify patients at risk for PTLD. Methods We studied EBER-1 gene expression in liver specimens obtained from 24 patients 2 days to 22 months before the development of PTLD, using in situ hybridization with an oligonucleotide probe. Control specimens were obtained from 20 recipients of allografts with signs of injury due to organ retrieval, acute graft rejection, or viral hepatitis in whom PTLD had not developed 9 to 71 months after the biopsy. Results Of the 24 patients with PTLD, 17 (71 percent) had specimens in which 1 to 40 percent of mononuclear cells were positive for the EBER-1 gene. In addition, 10 of these 17 patients (59 percent) had specimens with histopathological changes suggestive of EBV hepatitis. In every case, EBER-1–positive cells were found within the lymphoproliferative lesions identified at autopsy. Only 2 of the 20 controls (10 percent) had specimens with EBER-1–positive cells (P< 0.001), and such cells were rare. Conclusions EBER-1 gene expression in liver tissue precedes the occurrence of clinical and histologic PTLD. The possibility of identifying patients at risk by the method we describe here and preventing the occurrence of PTLD by a timely reduction of immunosuppression needs to be addressed by future prospective studies. PMID:1331789

  13. Epstein–Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8–9 September 2008

    PubMed Central

    Cohen, J. I.; Kimura, H.; Nakamura, S.; Ko, Y.-H.; Jaffe, E. S.

    2009-01-01

    Background: Recently novel Epstein–Barr virus (EBV) lymphoproliferative diseases (LPDs) have been identified in non-immunocompromised hosts, both in Asia and Western countries. These include aggressive T-cell and NK-cell LPDs often subsumed under the heading of chronic active Epstein–Barr virus (CAEBV) infection and EBV-driven B-cell LPDs mainly affecting the elderly. Design: To better define the pathogenesis, classification, and treatment of these disorders, participants from Asia, The Americas, Europe, and Australia presented clinical and experimental data at an international meeting. Results: The term systemic EBV-positive T-cell LPD, as adopted by the WHO classification, is preferred as a pathological classification over CAEBV (the favored clinical term) for those cases that are clonal. The disease has an aggressive clinical course, but may arise in the background of CAEBV. Hydroa vacciniforme (HV) and HV-like lymphoma represent a spectrum of clonal EBV-positive T-cell LPDs, which have a more protracted clinical course; spontaneous regression may occur in adult life. Severe mosquito bite allergy is a related syndrome usually of NK cell origin. Immune senescence in the elderly is associated with both reactive and neoplastic EBV-driven LPDs, including EBV-positive diffuse large B-cell lymphomas. Conclusion: The participants proposed an international consortium to facilitate further clinical and biological studies of novel EBV-driven LPDs. PMID:19515747

  14. A PLC-?1-independent, RasGRP1-ERK dependent pathway drives lymphoproliferative disease in LAT-Y136F mutant mice

    PubMed Central

    Kortum, Robert L.; Rouquette-Jazdanian, Alexandre K.; Miyaji, Michihiko; Merrill, Robert K.; Markegard, Evan; Pinski, John M.; Wesselink, Amelia; Nath, Nandan N.; Alexander, Clayton P.; Li, Wenmei; Kedei, Noemi; Roose, Jeroen P.; Blumberg, Peter M.; Samelson, Lawrence E.; Sommers, Connie L.

    2012-01-01

    Mice expressing a germline mutation in the PLC-?1 binding site of LAT (linker for activation of T cells) show progressive lymphoproliferation and ultimately die at 4–6 months of age. The hyper-activated T cells in these mice show defective TCR-induced calcium flux, but enhanced Ras/ERK activation that is critical for disease progression. Despite the loss of LAT-dependent PLC-?1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major RasGEF responsible for ERK activation and the lymphoproliferative phenotype in these mice. Analysis of isolated CD4+ T cells from LAT-Y136F mice showed altered proximal TCR-dependent kinase signaling, which activated a Zap70- and LAT-independent pathway. Moreover, LAT-Y136F T cells showed ERK activation that was dependent on Lck and/or Fyn, PKC?, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting. PMID:23209318

  15. The translation inhibitor silvestrol exhibits direct anti-tumor activity while preserving innate and adaptive immunity against EBV-driven lymphoproliferative disease.

    PubMed

    Patton, John T; Lustberg, Mark E; Lozanski, Gerard; Garman, Sabrina L; Towns, William H; Drohan, Callie M; Lehman, Amy; Zhang, Xiaoli; Bolon, Brad; Pan, Li; Kinghorn, A Douglas; Grever, Michael R; Lucas, David M; Baiocchi, Robert A

    2015-02-20

    Treatment options for patients with Epstein-Barr Virus-driven lymphoproliferative diseases (EBV-LPD) are limited. Chemo-immunotherapeutic approaches often lead to immune suppression, risk of lethal infection and EBV reactivation, thus it is essential to identify agents that can deliver direct anti-tumor activity while preserving innate and adaptive host immune surveillance. Silvestrol possesses direct anti-tumor activity in multiple hematologic malignancies while causing minimal toxicity to normal mononuclear cells. However, the effects of silvestrol on immune function have not been described. We utilized in vitro and in vivo models of EBV-LPD to simultaneously examine the impact of silvestrol on both tumor and normal immune function. We show that silvestrol induces direct anti-tumor activity against EBV-transformed lymphoblastoid cell lines (LCL), with growth inhibition, decreased expression of the EBV oncogene latent membrane protein-1, and inhibition of the downstream AKT, STAT1 and STAT3 signaling pathways. Silvestrol promoted potent indirect anti-tumor effects by preserving expansion of innate and EBV antigen-specific adaptive immune effector subsets capable of effective clearance of LCL tumor targets in autologous co-cultures. In an animal model of spontaneous EBV-LPD, silvestrol demonstrated significant therapeutic activity dependent on the presence of CD8-positive T-cells. These findings establish a novel immune-sparing activity of silvestrol, justifying further exploration in patients with EBV-positive malignancies. PMID:25393910

  16. The translation inhibitor silvestrol exhibits direct anti-tumor activity while preserving innate and adaptive immunity against EBV-driven lymphoproliferative disease

    PubMed Central

    Patton, John T.; Lustberg, Mark E.; Lozanski, Gerard; Garman, Sabrina L.; Towns, William H.; Drohan, Callie M.; Lehman, Amy; Zhang, Xiaoli; Bolon, Brad; Pan, Li; Kinghorn, A. Douglas; Grever, Michael R.

    2015-01-01

    Treatment options for patients with Epstein-Barr Virus-driven lymphoproliferative diseases (EBV-LPD) are limited. Chemo-immunotherapeutic approaches often lead to immune suppression, risk of lethal infection and EBV reactivation, thus it is essential to identify agents that can deliver direct anti-tumor activity while preserving innate and adaptive host immune surveillance. Silvestrol possesses direct anti-tumor activity in multiple hematologic malignancies while causing minimal toxicity to normal mononuclear cells. However, the effects of silvestrol on immune function have not been described. We utilized in vitro and in vivo models of EBV-LPD to simultaneously examine the impact of silvestrol on both tumor and normal immune function. We show that silvestrol induces direct anti-tumor activity against EBV-transformed lymphoblastoid cell lines (LCL), with growth inhibition, decreased expression of the EBV oncogene latent membrane protein-1, and inhibition of the downstream AKT, STAT1 and STAT3 signaling pathways. Silvestrol promoted potent indirect anti-tumor effects by preserving expansion of innate and EBV antigen-specific adaptive immune effector subsets capable of effective clearance of LCL tumor targets in autologous co-cultures. In an animal model of spontaneous EBV-LPD, silvestrol demonstrated significant therapeutic activity dependent on the presence of CD8-positive T-cells. These findings establish a novel immune-sparing activity of silvestrol, justifying further exploration in patients with EBV-positive malignancies. PMID:25393910

  17. Outcome of Rapamycin Therapy for Post-Transplant-Lymphoproliferative Disorder after Kidney Transplantation: Case Series

    PubMed Central

    Ashrafi, Farzaneh; Shahidi, Shahrzad; Mortazavi, Mojgan

    2015-01-01

    ABSTRACT Background Post-transplant lymphoproliferative disorders (PTLD) are a complication of chronic immunosuppressive therapy in solid organ transplantation with a high mortality rate. Alternative treatments such as rapamycin have been explored. Methods: A detailed retrospective analysis was performed according to data collected from 13 patients with PTLD. At the time of PTLD diagnosis, immunosuppressive therapy was decreased and rapamycin administered. Overall survival, disease-free survival of patients and graft survival were determined. Results: Among 590 kidney transplant recipients, 13 adult patients with PTLD were included in this study. The mean age of the patients was 42.15 (range: 25–58) years at the time of PTLD diagnosis, and 9 patients were male. Histology was distributed in 9 diffuse large B cell, 1 Malt lymphoma, 1 Burkitt lymphoma, 2 Hodgkin-like PTLD. The response rate to rapamycin alone was 30.8%. The mean overall survival period was 23.38 months and 11 patients are still alive. In total, 10 patients (76.9%) achieved a complete remission with functioning graft in 11 (84.6%) patients. Conclusion: Despite the retrospective focus and limited number of patients, this study provides promising results regarding the effectiveness of stopping calcineurin inhibitors and switching to rapamycin for patients with PTLD. PMID:25802698

  18. Antigen-specific lymphoproliferative responses to tetanus toxoid: a means for the evaluation of Marek's disease virus-induced immunosuppression in chickens

    Microsoft Academic Search

    S. K. Reddy; M. Suresh; K. Karaca; J. M. Sharma; J. McMillen; R. D. Schwartz

    1996-01-01

    Antigen-specific lymphoproliferative responses were examined in chickens following immunization with tetanus toxoid (Ttx). The immune competence of chickens was assessed by mitogen assay utilizing phytohemagglutinin (PHA)-stimulation and Ttx-specific antigen proliferation assay (Ttx-APA). Immune spleen cells but not peripheral blood leucocytes demonstrated specific proliferation following stimulation in vitro in a Ttx-APA. In this study, we examined firstly the effects of Marek's

  19. Posttransplant Diabetes in Kidney Transplant Recipients

    Microsoft Academic Search

    Eli A. Friedman; Tai-ping Shyh; Monica M. Beyer; Thomas Manis; Khalid M. H. Butt

    1985-01-01

    We retrospectively reviewed the course of 1,000 renal transplants performed in 835 recipients (758 non-diabetics) to assess the incidence of new onset posttransplant diabetes in former nondiabetics. A total of 119 (15.7%) recipients manifested posttransplant diabetes, of whom 64 (53.8%) became hyperglycemic within 3 weeks of transplantation. Actuarial survival analysis indicated a statistically significant selection of blacks; 68 (57.1 %)

  20. [Advances in the knowledge and management of autoimmune lymphoproliferative syndrome].

    PubMed

    Garrido Colino, C

    2014-02-01

    Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to maintain lymphocyte homeostasis. ALPS often manifest in childhood with cytopenias, chronic non-malignant lymphoproliferation and autoimmune complications. A number of new insights have improved the understanding of the genetics and biology of ALPS. The treatment of the disease has changed and mycophenolate mofetil and sirolimus have been demonstrated to have marked activity against the disease, improving quality of life for many patients. These will be discussed in this review. PMID:24055319

  1. Renal transplantation in the modern immunosuppressive era in Spain: four-year results from a multicenter database focus on post-transplant cardiovascular disease

    Microsoft Academic Search

    Jose M Morales; Roberto Marcén; Amado Andrés; Miguel González Molina; Domingo del Castillo; Mercedes Cabello; Luis Capdevila; Josep M Campistol; Federico Oppenheimer; Daniel Serón; Salvador Gil Vernet; Ildefonso Lampreave; Francisco Valdés; Fernando Anaya; Fernando Escuín; Manuel Arias; Luis Pallardó; Jesús Bustamante

    2008-01-01

    To evaluate cardiovascular disease (CVD) after renal transplantation we established a CVD database (no-intervention) including all patients transplanted among 2000–2002 in 14 hospitals from Spain (Renal Forum Group) (n=2600). They were prospective followed annually thereafter and we present herein the most important results concerning survival figures and CVD at four years. Mean recipient age was 49.7±13.7 years: 16% retransplanted and

  2. A phospholipase C-?1-independent, RasGRP1-ERK-dependent pathway drives lymphoproliferative disease in linker for activation of T cells-Y136F mutant mice.

    PubMed

    Kortum, Robert L; Rouquette-Jazdanian, Alexandre K; Miyaji, Michihiko; Merrill, Robert K; Markegard, Evan; Pinski, John M; Wesselink, Amelia; Nath, Nandan N; Alexander, Clayton P; Li, Wenmei; Kedei, Noemi; Roose, Jeroen P; Blumberg, Peter M; Samelson, Lawrence E; Sommers, Connie L

    2013-01-01

    Mice expressing a germline mutation in the phospholipase C-?1-binding site of linker for activation of T cells (LAT) show progressive lymphoproliferation and ultimately die at 4-6 mo age. The hyperactivated T cells in these mice show defective TCR-induced calcium flux but enhanced Ras/ERK activation, which is critical for disease progression. Despite the loss of LAT-dependent phospholipase C-?1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major Ras guanine exchange factor responsible for ERK activation and the lymphoproliferative phenotype in these mice. Analysis of isolated CD4(+) T cells from LAT-Y136F mice showed altered proximal TCR-dependent kinase signaling, which activated a Zap70- and LAT-independent pathway. Moreover, LAT-Y136F T cells showed ERK activation that was dependent on Lck and/or Fyn, protein kinase C-?, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting. PMID:23209318

  3. Pure Red Cell Aplasia and Lymphoproliferative Disorders: An Infrequent Association

    PubMed Central

    Vlachaki, Efthymia; Diamantidis, Michael D.; Klonizakis, Philippos; Haralambidou-Vranitsa, Styliani; Ioannidou-Papagiannaki, Elizabeth; Klonizakis, Ioannis

    2012-01-01

    Pure red cell aplasia (PRCA) is a rare bone marrow failure syndrome defined by a progressive normocytic anaemia and reticulocytopenia without leukocytopenia and thrombocytopenia. Secondary PRCA can be associated with various haematological disorders, such as chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma (NHL). The aim of the present review is to investigate the infrequent association between PRCA and lymphoproliferative disorders. PRCA might precede the appearance of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or might appear following the lymphomatic disorder. Possible pathophysiological molecular mechanisms to explain the rare association between PRCA and lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be autoimmune mediated by antibodies against either erythroblasts or erythropoietin, by T-cells secreting factors selectively inhibiting erythroid colonies in the bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given to the therapeutical approach, as several treatment regimens have failed for PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving anaemia in the majority of patients with lymphoma-associated PRCA. Further investigation is required to define the pathophysiology of PRCA at a molecular level and to provide convincing evidence why it might appear as a rare complication of lymphoproliferative disorders. PMID:22593689

  4. Primary central nervous system posttransplantation lymphoproliferative disorder after heart and lung transplantation.

    PubMed

    Gifford, G; Fay, K; Jabbour, A; Ma, D D

    2015-05-01

    Primary central nervous system posttransplantation lymphoproliferative disorder (PCNS-PTLD) is uncommon, especially after heart or lung transplantation. Database analysis from a single heart and lung transplantation centre and a literature review pertaining to PCNS-PTLD was performed. In this study, the prevalence of PCNS-PTLD was 0.18% after heart and/or lung transplants. Of 1674 transplants, three cases of PCNS-PTLD developed 14 months, 9 years and 17 years posttransplant, and all were Epstein-Barr virus driven malignancies. Literature review of the topic revealed predominantly retrospective studies, with most reported cases after renal transplantation. The overall survival is poor, and it may be improved by early diagnosis and treatment. There are no published guidelines on the management of PCNS-PTLD; immune-chemotherapy in conjunction with reduction of immune suppression is preferred based on available evidence. PMID:25955465

  5. Recognizing and treating secondary immune thrombocytopenic purpura associated with lymphoproliferative disorders.

    PubMed

    Liebman, Howard A

    2009-01-01

    Immune thrombocytopenic purpura (ITP), a condition of low platelets, can occur from primary causes, often referred to as idiopathic thrombocytopenic purpura, or secondary to an underlying disease, such as an autoimmune disorder or an infection. Secondary ITP can also occur with lymphoproliferative malignancies, such as chronic lymphocytic leukemia (CLL), Hodgkin's disease (HD), and non-Hodgkin's lymphomas (NHL). ITP associated with lymphoproliferative disorders has the same mechanism of platelet destruction as in idiopathic or primary ITP. The current treatment paradigm for secondary ITP varies according to the underlying condition. Standard treatments for primary ITP, which include corticosteroids, intravenous immunoglobulin (IVIg), anti-D, and splenectomy, are often successful in secondary ITP. However, in most situations with secondary ITP, treatment should focus on resolving the underlying disorder before treating the shortage of platelets, and, in the circumstances of ITP developing in patients with lymphoproliferative disorders, responses are frequently linked to remission of the primary malignancy. PMID:19245932

  6. Lymphoproliferative disorders in chronic hepatitis C.

    PubMed

    Idilman, R; Colantoni, A; De Maria, N; Alkan, S; Nand, S; Van Thiel, D H

    2004-07-01

    Chronic hepatitis C virus (HCV) infection is associated with the development of lymphoproliferative disorders (LPDs). The aim of this investigation was to determine the prevalence and characterization of monoclonal gammopathy and benign and malignant LPDs in individuals with chronic hepatitis C. A total of 233 subjects diagnosed with chronic hepatitis C (male/female ratio: 131/102, median age; 49 years) were studied. Serum and urine were examined for the presence of a monoclonal gammopathy. A bone marrow aspirate and biopsy was obtained in individuals with a monoclonal gammopathy. Thirty-two patients (13.7%, 32 of 233) had a monoclonal gammopathy; 75% of them were benign and were not associated with malignant disorders (24 of 32) while 25% were associated with malignant LPDs or a plasma cell disorder (eight of 32). Two additional subjects without monoclonal gammopathy were diagnosed as having a malignant LPDs. The prevalence of malignant LPDs/plasma cell disorder in individuals with HCV-induced chronic liver disease was 4.3%. No difference was found in terms of disease duration, HCV genotype, viral load, alanine aminotransferase level or histopathologic score between the subjects with or without a monoclonal gammopathy. The presence of mixed cryoglobulinaemia was strongly associated with the presence of an underlying malignant disorder. Hence a monoclonal gammopathy is found in 14% of patients with chronic hepatitis C and is associated with malignant B-cell LPD in more than a quarter of such patients. The prevalence of LPDs in individuals with HCV-induced chronic liver disease is greater than that of the normal healthy population. PMID:15230852

  7. Autoimmune lymphoproliferative syndrome-like syndrome presented as lupus-like syndrome with mycobacterial joint infection evolved into the lymphoma

    Microsoft Academic Search

    Young Hoon Hong; Choong Ki Lee

    2009-01-01

    The autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like syndrome are variable clinical conditions characterized by\\u000a lymphoproliferative disease, autoimmune cytopenias and susceptibility to malignancy. A 59-year-old woman was admitted to the\\u000a hospital for intractable generalized pain and stiffness with multiple swollen joints for 2 weeks. A low-grade fever, intermittent\\u000a hypotension and confusion were associated with the pain. The evaluation revealed multiple joint bony

  8. Cryofibrinogenemia After a Liver Transplant: First Reported Case Posttransplant and a Case-Based Review of the Nontransplant Literature.

    PubMed

    Chen, Yuanyuan; Sreenivasan, Gayatri M; Shojania, Kam; Yoshida, Eric M

    2015-06-01

    Cryofibrinogenemia is a rare disorder in which plasma, not serum, forms a cryoprecipitate. Patients with cryofibrinogenemia may be asymptomatic, or they may have painful ulcers, purpura, livedo reticularis, Raynaud phenomenon, perniosis of the extremities, thrombosis, and arthralgia. Cryofibrinogenemia may be primary or secondary to an underlying disorder such as connective tissue disease, malignancy, infection, drugs, or thromboembolic disease. Here, we present a 41-year-old woman with a pancreatic neuroendocrine tumor who underwent a Whipple procedure in 2003 followed by 2 liver transplants for hepatic metastases. Three years posttransplant, we discovered a biopsy-proven metastatic lesion in her femur. Five years posttransplant, she developed acute, severe pain in both feet, and was found to have cryofibrinogenemia despite immunosuppression post-transplant. Testing for connective tissue diseases and hematologic malignancy were negative. She was treated with high-dose prednisone, which completely resolved her symptoms. We also conducted a review of the literature via a PubMed search to summarize the association of cryofibrinogenemia with malignancy and treating cryofibrinogenemia with corticosteroids. Our study is the first reported case of cryofibrinogenemia that developed secondary to a neuroendocrine tumor posttransplant. Our report suggests that cryofibrinogenemia may occur despite immunosuppression adequate to prevent graft rejection, and that high-dose corticosteroids are an effective treatment for posttransplant cryofibrinogenemia. PMID:24679054

  9. Autoimmune Lymphoproliferative Syndrome Misdiagnosed as Hemophagocytic Lymphohistiocytosis

    PubMed Central

    Rudman Spergel, Amanda; Walkovich, Kelly; Price, Susan; Niemela, Julie E.; Wright, Dowain; Fleisher, Thomas A.

    2013-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder of apoptosis, most commonly due to mutations in the FAS (TNFRSF6) gene. It presents with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage cytopenias in an otherwise healthy child. Unfortunately, these clinical findings are also noted in other childhood lymphoproliferative conditions, such as leukemia, lymphoma, and hemophagocytic lymphohistiocytosis, which can confound the diagnosis. This report describes a 6-year-old girl with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis and treated with chemotherapy before the recognition that her symptoms and laboratory values were consistent with a somatic FAS mutation leading to ALPS. This case should alert pediatricians to include ALPS in the differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenias; obtain discriminating screening laboratory biomarkers, such as serum vitamin B-12 and ferritin levels; and, in the setting of a highly suspicious clinical scenario for ALPS, pursue testing for somatic FAS mutations when germ-line mutation testing is negative. PMID:24101757

  10. Initial Steroid Sensitivity in Children with Steroid-Resistant Nephrotic Syndrome Predicts Post-Transplant Recurrence

    PubMed Central

    Ding, Wen Y.; Koziell, Ania; McCarthy, Hugh J.; Bierzynska, Agnieszka; Bhagavatula, Murali K.; Dudley, Jan A.; Inward, Carol D.; Coward, Richard J.; Tizard, Jane; Reid, Christopher; Antignac, Corinne; Boyer, Olivia

    2014-01-01

    Of children with idiopathic nephrotic syndrome, 10%–20% fail to respond to steroids or develop secondary steroid resistance (termed initial steroid sensitivity) and the majority progress to transplantation. Although 30%–50% of these patients suffer disease recurrence after transplantation, with poor long-term outcome, no reliable indicator of recurrence has yet been identified. Notably, the incidence of recurrence after transplantation appears reduced in patients with steroid-resistant nephrotic syndrome (SRNS) due to monogenic disorders. We reviewed 150 transplanted patients with SRNS to identify biomarkers that consistently predict outcome of SRNS after transplantation. In all, 25 children had genetic or familial SRNS and did not experience post-transplant recurrence. We reviewed phenotypic factors, including initial steroid sensitivity, donor type, age, ethnicity, time to ESRD, and time on dialysis, in the remaining 125 children. Of these patients, 57 (45.6%) developed post-transplant recurrence; 26 of 28 (92.9%) patients with initial steroid sensitivity recurred after transplantation, whereas only 26 of 86 (30.2%) patients resistant from the outset recurred (odds ratio, 30; 95% confidence interval, 6.62 to 135.86; P<0.001). We were unable to determine recurrence in two patients (one with initial steroid sensitivity), and nine patients did not receive initial steroids. Our data show that initial steroid sensitivity is highly predictive of post-transplant disease recurrence in this pediatric patient population. Because a pathogenic circulating permeability factor in nephrotic syndrome remains to be confirmed, we propose initial steroid sensitivity as a surrogate marker for post-transplant recurrence. PMID:24511128

  11. [KHSV/EBV associated germinotropic lymphoproliferative disorder: a rare entity, case report and review of the literature].

    PubMed

    Taris, Michaël; de Mascarel, Antoine; Riols, Mercédčs; Delwail, Vincent; Milpied, Noël; Dubus, Pierre; Parrens, Marie

    2014-10-01

    We report a case of KSHV/EBV associated germinotropic lymphoproliferative disorder (LPG) in a 49-year-old African patient, without immunosuppression. LPG is a rare entity arising in immunocompetent patients in opposition to other lymphoproliferative disorders associated to Kaposi sarcoma-associated herpes virus (KSHV). The disease presents itself as localized lymphadenopathy with an infiltration of germinal centers by plasmablastic cells coinfected by KSHV and EBV (Epstein-Barr Virus). After treatment, the outcome is favorable. Differential diagnosis in our case, due to the presence of clusters of Hodgkin-like cells in the mantle zone, included lymphocyte rich classic Hodgkin lymphoma (LHCRL) and nodular lymphocyte predominant Hodgkin lymphoma (LHNPL). Finally, we highlight the differential diagnostic criteria of KSHV lymphoproliferative diseases. PMID:25439990

  12. Bridge to lung transplantation and rescue post-transplant: the expanding role of extracorporeal membrane oxygenation

    PubMed Central

    Gulack, Brian C.; Hirji, Sameer A.

    2014-01-01

    Over the last several decades, the growth of lung transplantation has been hindered by a much higher demand for donor lungs than can be supplied, leading to considerable waiting time and mortality among patients waiting for transplant. This has led to the search for an alternative bridging strategy in patients with end-stage lung disease. The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation as well as a rescue strategy post-transplant for primary graft dysfunction (PGD) has been studied previously, however due to initially poor outcomes, its use was not heavily instituted. In recent years, with significant improvement in technologies, several single and multi-center studies have shown promising outcomes related to the use of ECMO as a bridging strategy as well as a therapy for patients suffering from PGD post-transplant. These results have challenged our current notion on ECMO use and hence forced us to reexamine the utility, efficacy and safety of ECMO in conjunction with lung transplantation. Through this review, we will address the various aspects related to ECMO use as a bridge to lung transplantation as well as a rescue post-transplant in the treatment of PGD. We will emphasize newer technologies related to ECMO use, examine recent observational studies and randomized trials of ECMO use before and after lung transplantation, and reflect upon our own institutional experience with the use of ECMO in these difficult clinical situations. PMID:25132974

  13. Predictive roles of intraoperative blood glucose for post-transplant outcomes in liver transplantation

    PubMed Central

    Park, Chul Soo

    2015-01-01

    Diabetogenic traits in patients undergoing liver transplantation (LT) are exacerbated intraoperatively by exogenous causes, such as surgical stress, steroids, blood transfusions, and catecholamines, which lead to intraoperative hyperglycemia. In contrast to the strict glucose control performed in the intensive care unit, no systematic protocol has been developed for glucose management during LT. Intraoperative blood glucose concentrations typically exceed 200 mg/dL in LT, and extreme hyperglycemia (> 300 mg/dL) is common during the neohepatic phase. Only a few retrospective studies have examined the relationship between intraoperative hyperglycemia and post-transplant complications, with reports of infectious complications or mortality. However, no prospective studies have been conducted regarding the influence of intraoperative hyperglycemia in LT on post-transplant outcome. In addition to absolute blood glucose values, the temporal patterns in blood glucose levels during LT may serve as prognostic features. Persistent neohepatic hyperglycemia (without a decline) throughout LT is a useful indicator of early graft dysfunction. Moreover, intraoperative variability in glucose levels may predict the need for reoperation for hemorrhage after LT. Thus, there is an urgent need for guidelines for glucose control in these patients, as well as prospective studies on the impact of glucose control on various post-transplant complications. This report highlights some of the recent studies related to perioperative blood glucose management focused on LT and liver disease. PMID:26078559

  14. Post-transplant adjustment--the later years.

    PubMed

    Fredericks, Emily M; Zelikovsky, Nataliya; Aujoulat, Isabelle; Hames, Anna; Wray, Jo

    2014-11-01

    As survival rates for pediatric solid organ transplantation have continued to improve, researchers and healthcare providers have increasingly focused on understanding and enhancing the HRQOL and psychosocial functioning of their patients. This manuscript reviews the psychosocial functioning of pediatric transplant recipients during the "later years," defined as more than three yr post-transplant, and focuses on the day-to-day impact of living with a transplant after the immediate period of adjustment and early years after surgery. Key topics reviewed include HRQOL, cognitive functioning, impact on the family, regimen adherence, and transition of responsibility for self-management tasks. Overall, pediatric transplant recipients evidence impairment in HRQOL, neuropsychological outcomes, and family functioning as compared to non-transplant recipients. However, the degree of impairment is influenced by a variety of factors including, disease severity, age, solid organ type, and study methodologies. Studies are limited by small samples, cross-sectional design, and the lack of universal assessment battery to allow for comparisons across solid organ populations. Areas for future research are discussed. PMID:25220845

  15. Epstein-Barr virus: dermatologic associations and implications: part II. Associated lymphoproliferative disorders and solid tumors.

    PubMed

    Eminger, Lindsay A; Hall, Lawrence David; Hesterman, Kathleen S; Heymann, Warren R

    2015-01-01

    Epstein-Barr virus (EBV) was the first human virus to be associated with oncogenesis. Over the past few decades, cumulative research has revealed that latent EBV infection may be implicated in the pathogenesis of a heterogeneous group of lymphoproliferative disorders and malignancies occurring in both immunocompetent and immunocompromised hosts. Many of these diseases have either primary or secondary cutaneous manifestations. Serologic studies and EBV-encoded RNA in situ hybridization stains have been used to show the association of EBV with disease; while these findings may imply a role, they do not equate with causation. In part II of this continuing medical education review, the salient features of EBV-associated lymphoproliferative disorders and solid tumors are detailed. PMID:25497918

  16. Urinary Calprotectin and Posttransplant Renal Allograft Injury

    PubMed Central

    Bistrup, Claus; Marcussen, Niels; Pagonas, Nikolaos; Seibert, Felix S.; Arndt, Robert; Zidek, Walter; Westhoff, Timm H.

    2014-01-01

    Objective Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. Methods In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. Results We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r?=??0.33; P<0.001). Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 m2 four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66). Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. Conclusions Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation. PMID:25402277

  17. A Case of Isolated Cardiac Hydatid Cyst that Mimics Lymphoproliferative Malignancy.

    PubMed

    Yildiz, Cenk Eray; Sinan, Ümit Ya?ar; Yildiz, Ahmet; Çetin, Gürkan; Küçüko?lu, Serdar

    2015-06-01

    Cardiac cystic echinococcosis is a rare parasitic infestation caused by Echinococcus granulosus larvae and it composes 0.5-2% of all human cystic echinococcosis cases. The left ventricle is the most common affected area followed by right ventricle, interventricular septum, left atrium, right atrium, and interatrial septum. The diagnosis is difficult because of nonspecific clinical and radiographic findings. We present a case of isolated apical cardiac cystic echinococcosis mimicking lymphoproliferative disease. PMID:25470654

  18. Rosette formation with mouse erythrocytes. III. Studies in patients with primary immunodeficiency and lymphoproliferative disorders.

    PubMed Central

    Gupta, S; Good, R A; Siegal, F P

    1976-01-01

    Rosette formation with mouse erythrocytes and other cell-surface markers were examined on lymphocytes from patients with a variety of primary immunodeficiency and lymphoproliferative disorders. Mouse erythrocyte rosette-forming cells and lymphocytes with surface immunoglobulins were regularly absent in patients with Bruton type agammaglobulinaemia, immunodeficiency and thymoma syndrome and severe combined immunodeficiency disease. However, they were present in normal or low numbers in patients with common variable immunodeficiency, selective IgA deficiency and ataxis telangiectasia. Lymphocytes from patients with acute lymphoblastic leukaemia Sezary syndrome and mycosis fungoides made no or few rosettes with mouse erythrocytes. Increased numbers of mouse erythrocyte rosette-forming cells were present in patients with chronic lymphocytic leukaemia and Waldenstrom's macroglobulinaemia. The significance of the mouse erythrocyte rosette as a B-cell marker in the analysis of primary immunodeficiency and lymphoproliferative disorders is discussed. PMID:1068759

  19. Induction and progression of human lymphoproliferative lesions by Epstein-Barr virus.

    PubMed Central

    Chappuis, B B; Müller-Hermelink, H K

    1990-01-01

    Epstein-Barr virus (EBV) is involved in numerous lymphoproliferative diseases. In addition to classical lesions such as endemic Burkitt's lymphoma and infectious mononucleosis, there are other disorders of the lymphoid system that are discussed in relation to EBV: B-cell lymphomas in immunosuppressed individuals. Hodgkin's disease and, to some extent, primary extranodal lymphomas. Studies of the EBV expression in classical and nonclassical lesions could lead to the better understanding of different EBV mechanisms in lymphomagenesis. Images FIGURE 1. FIGURE 2. PMID:2176977

  20. [Benign lymphoproliferative lesions of the parotid gland in HIV infection].

    PubMed

    Cecconi, L; Busi Rizzi, E; Schininŕ, V; Mazzuoli, G

    1996-01-01

    The authors investigated the role of ultrasonography (US) as the method of choice in diagnosing parotid lesions in HIV+ patients. Bilateral parotid gland enlargement associated with laterocervical lymph node enlargement is a sign of HIV infection. This pathologic condition is observed in 2-10% of seropositive patients. Histology demonstrates benign lymphoproliferative lesions referrable to immune system activation. Our series consisted of 37 HIV+ patients monitored with US for a year, all patients had cytologic confirmation of their disease, with needle biopsy in 9 patients and with MR studies in 4 patients. US showed focal solid lesions, with cystic and mixed appearance in the 26 adult subjects and gross parenchymal inhomogeneity in the 11 children; laterocervical lymph node enlargement was associated in 31 cases. In the only two cases with unilateral parotid involvement, an abscess and a lymphoma were diagnosed. To conclude, US findings in HIV+ patients, although aspecific, can help make the correct diagnosis, if they are integrated with the patient's history and clinical findings. PMID:8966280

  1. Pretransplant cardiovascular evaluation and posttransplant cardiovascular risk

    Microsoft Academic Search

    James B Young; Hans-Hellmut Neumayer; Robert D Gordon

    2010-01-01

    Modern immunosuppression has expanded access to kidney transplantation by limiting the risk of rejection. However, cardiovascular disease (CVD) remains the principal cause of death with a functioning graft, threatening the long-term survival of transplant recipients. The article reviews the leading risk factors for cardiovascular morbidity both before and after kidney transplantation. Evidence linking poor renal function to CVD is discussed.

  2. How I treat autoimmune lymphoproliferative syndrome

    PubMed Central

    Oliveira, Joăo Bosco

    2011-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to maintain lymphocyte homeostasis, permitting accumulation of lymphoid mass and persistence of autoreactive cells that often manifest in childhood with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and recurring multilineage cytopenias. Cytopenias in these patients can be the result of splenic sequestration as well as autoimmune complications manifesting as autoimmune hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. More than 300 families with hereditary ALPS have now been described; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years by our colleagues and ourselves. Some of these patients with FAS mutations affecting the intracellular portion of the FAS protein also have an increased risk of B-cell lymphoma. The best approaches to diagnosis, follow-up, and management of ALPS, its associated cytopenias, and other complications resulting from infiltrative lymphoproliferation and autoimmunity are presented. This trial was registered at www.clinicaltrial.gov as #NCT00001350. PMID:21885601

  3. [Autoimmune and lymphoproliferative HCV-correlated manifestations: example of mixed cryoglobulinaemia (review)].

    PubMed

    Ghinoi, A; Mascia, M T; Puccini, R; Ferri, C

    2004-01-01

    Mixed cryoglobulinaemia (MC) is a systemic vasculitis involving small vessels (arterioles, capillaries, venules). The histological hallmark of the disease is the leukocytoclastic vasculitis secondary to the vascular deposition of circulating immune-complexes (CIC), mainly cryoglobulins and complement. The immune-mediated vasculitic lesions are responsible for different MC clinical features, including cutaneous and visceral organ involvement. Hepatitis C virus (HCV) represents the triggering factor in the large majority of MC patients (>90%). Moreover, several epidemiological, clinico-pathological and laboratory investigations suggested a possible role for HCV in a wide spectrum of immuno-lymphoproliferative disorders; namely, porphyria cutanea tarda, diabetes, polyarthritis, lung fibrosis, poly-dermatomyositis, thyroiditis, thyroid cancer, B-cell non-Hodgkin's lymphomas (B-NHL), etc. Renal involvement with or without MC syndrome can be observed in HCV-infected individuals. There is great geographical etherogeneity in the prevalence of HCV-related disorders. This epidemiological observation suggests a multifactorial and multistep process in the pathogenesis of these conditions, involving other unknown genetic and/or environmental factors. HCV lymphotropism may explain the mono-oligoclonal B-lymphocyte expansion observed in HCV-infected individuals, particularly in MC patients. The 'benign' lymphoproliferative disorder, classified as monotypic lymphoproliferative disorders of undetermined significance (MLDUS), may be responsible for the wide production of CIC, including cryoglobulins, rheumatoid factor and different organ and non-organ specific autoantibodies. The consequence is the appearance of various HCV-related autoimmune diseases, including MC syndrome. This latter may be complicated by B-NHL in 10% of the cases; moreover, HCV infection has been confirmed in a significant percentage of 'idiopathic B-NHL. For a correct therapeutic approach to cryoglobulinaemic vasculitis, as well as to other HCV-related disorders, we should deal with concomitant, conflicting conditions: HCV infection, autoimmune and lymphoproliferative alterations. In this scenario, we can treat the diseases at three different levels by means of etiologic, pathogenetic and/or symptomatic therapies. The eradication of HCV by combined interferon and ribavirin therapy can be achieved in only a minority of cases. On the contrary, severe complications such as glomerulonephritis, sensory-motor neuropathy or diffuse vasculitis can be effectively treated by a combination of corticosteroids, plasma exchange and cyclophosphamide. More recently, a pathogenetic treatment with rituximab, a monoclonal chimeric antibody that binds to the B-cell surface antigen CD20 with selective B-cell blockade, was proposed in patients with HCV-related MC syndrome. PMID:15285001

  4. Variations of the UNC13D Gene in Patients with Autoimmune Lymphoproliferative Syndrome

    PubMed Central

    Aricň, Maurizio; Boggio, Elena; Cetica, Valentina; Melensi, Matteo; Orilieri, Elisabetta; Clemente, Nausicaa; Cappellano, Giuseppe; Buttini, Sara; Soluri, Maria Felicia; Comi, Cristoforo; Dufour, Carlo; Pende, Daniela; Dianzani, Irma; Ellis, Steven R.; Pagliano, Sara; Marcenaro, Stefania; Ramenghi, Ugo; Chiocchetti, Annalisa; Dianzani, Umberto

    2013-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is caused by genetic defects decreasing Fas function and is characterized by lymphadenopathy/splenomegaly and expansion of CD4/CD8 double-negative T cells. This latter expansion is absent in the ALPS variant named Dianzani Autoimmune/lymphoproliferative Disease (DALD). In addition to the causative mutations, the genetic background influences ALPS and DALD development. We previously suggested a disease-modifying role for the perforin gene involved in familial hemophagocytic lymphohistiocytosis (FHL). The UNC13D gene codes for Munc13-4, which is involved in perforin secretion and FHL development, and thus, another candidate for a disease-modifying role in ALPS and DALD. In this work, we sequenced UNC13D in 21 ALPS and 20 DALD patients and compared these results with sequences obtained from 61 healthy subjects and 38 multiple sclerosis (MS) patients. We detected four rare missense variations in three heterozygous ALPS patients carrying p.Cys112Ser, p.Val781Ile, and a haplotype comprising both p.Ile848Leu and p.Ala995Pro. Transfection of the mutant cDNAs into HMC-1 cells showed that they decreased granule exocytosis, compared to the wild-type construct. An additional rare missense variation, p.Pro271Ser, was detected in a healthy subject, but this variation did not decrease Munc13-4 function. These data suggest that rare loss-of-function variations of UND13D are risk factors for ALPS development. PMID:23840885

  5. Ptaquiloside-induced, B-cell lymphoproliferative and early-stage urothelial lesions in mice.

    PubMed

    Gil da Costa, Rui M; Oliveira, Paula A; Vilanova, Manuel; Bastos, Margarida M S M; Lopes, Célia C; Lopes, Carlos

    2011-11-01

    Bracken (Pteridium aquilinum) has long been known to cause cancer in farm and laboratory animals. Ptaquiloside, a norsesquiterpene glycoside found in bracken, is considered its main carcinogenic toxin and is capable of inducing tumours in a variety of organ systems, but especially in the urinary bladder, depending on the animal species, the administration route employed and the duration of exposure. In the present study, 12 male CD-1 mice were intraperitoneally administered with 0.5 mg ptaquiloside weekly for 15 weeks, followed by 15 weeks without any treatment. Twelve animals used as controls were administered the vehicle solution (phosphate buffered saline). Two exposed animals died during the experimental work. On necropsy, blood and tissue samples (brain, eyes, thymus, heart, lungs, liver, digestive system, spleen, bladder, kidney, adrenal gland, urinary bladder, sexual accessory glands, testes, muscle, skin and femur) were collected for histological analysis. Leukograms were prepared from blood smears and total WBC counts obtained with a Neubauer chamber. Flow cytometry was used to assess blood T-(CD3(+)) and B-(CD19(+))-lymphocytes, medullary granulocytic (CD11b(+)/Ly-6G(-), CD11b(+)/Ly-6G(+)) and lymphocytic (CD19(+)/IgM(-), CD19+/IgM(+)) populations and thymic lymphoid (CD4(+), CD8(+), CD4(+)/CD8(+)) populations. Lymphoproliferative lesions were analysed immunohistochemically using antibodies against CD45R and CD3. All of the 10 surviving mice developed a lymphoproliferative malignancy. Lymphoproliferative disease was characterized by multifocal B-(CD45(+)/CD3(-))-lymphocytic renal (10/10 animals) and hepatic (2/10 animals) invasion, splenic white pulp hyperplasia (10/10) together with a significant increase in circulating B-(CD19(+))-lymphocytes and the appearance of circulating dysplastic lymphoid cells. Eight out of 10 ptaquiloside-exposed animals developed urothelial dysplasia (six low-grade dysplasia and two high-grade dysplasia). No lesions were detected in control mice. These results show that ptaquiloside is capable of inducing malignant transformation in mice and provide an in-depth characterisation of lymphoproliferative lesions. Furthermore, the urinary bladder is shown to be a target organ for this toxin in mice as well as in other animal species. PMID:21907228

  6. Hepatitis C management in post-transplant patients.

    PubMed

    Hilgenfeldt, E; Firpi, R J

    2015-03-01

    Hepatitis C virus (HCV)-related cirrhosis is the leading cause for liver transplantation (LT) in developed countries. One of the most troubling complications following LT in patients with HCV is that of recurrence. Unfortunately, this occurs in nearly all patients with HCV. Patients suffering recurrence are known to have faster times to fibrosis and consequently higher rates of graft failure. In general, patients whom undergo transplantation for HCV cirrhosis have higher mortalities comparatively. It is for this reason that HCV in post-transplant patients must be strictly monitored for and treated. Until recently, treatment with standard therapy or pegylated interferon and ribavirin was only marginally effective and the use in this population was off-label. With the advent of direct acting antivirals (DAA), hopes for improved sustained virologic response (SVR) exists. This review will attempt to provide an update regarding recent data for HCV treatment in post-transplant patients, and by doing so, hopefully shed light on a previously dim and dreaded illness. PMID:25390286

  7. Post-transplant acute renal failure in cadaver renal recipients treated with cyclosporine

    Microsoft Academic Search

    Bruce M Hall; David J Tiller; Geoffrey G Duggin; John S Horvath; Annabelle Farnsworth; James May; James R Johnson; A G Ross Sheil

    1985-01-01

    Post-transplant acute renal failure in cadaver renal recipients treated with cyclosporine. The outcome of patients with acute renal failure following cadaveric renal transplant has been evaluated in a prospective, controlled trial, comparing treatment with cyclosporine (CSA) to prednisone, azathioprine, and antilymphocyte globulin (AZA). There was a high incidence of acute post-transplant renal failure in both groups: 37 of 51 CSA

  8. Posttransplantation lymphoproliferative disorders in pediatric thoracic organ recipients

    Microsoft Academic Search

    Gerard J. Boyle; Marian G. Michaels; Steven A. Webber; A. S. Knisely; Geoffrey Kurland; Lynne A. Cipriani; Bartley P. Griffith; Frederick J. Fricker

    1997-01-01

    Objective: To determine the frequency, predisposing factors, clinical presentation, and outcome of posttransplantation lymphoproliferative disorders (PTLDs) in pediatric thoracic organ transplant recipients.Methods: Retrospective review of the medical records of all 120 children who survived longer than 1 month after thoracic organ transplantation at our center.Results: PTLD was diagnosed in 14 patients (11.7%), including 7.7% of heart and 19.5% of heart-lung\\/lung

  9. Gray's Time-Varying Coefficients Model for Posttransplant Survival of Pediatric Liver Transplant Recipients with a Diagnosis of Cancer

    PubMed Central

    Chang, Chung-Chou H.; Tomko, Heather E.; Donnell, Drew Michael S.; Roberts, Mark S.; Bryce, Cindy L.

    2013-01-01

    Transplantation is often the only viable treatment for pediatric patients with end-stage liver disease. Making well-informed decisions on when to proceed with transplantation requires accurate predictors of transplant survival. The standard Cox proportional hazards (PH) model assumes that covariate effects are time-invariant on right-censored failure time; however, this assumption may not always hold. Gray's piecewise constant time-varying coefficients (PC-TVC) model offers greater flexibility to capture the temporal changes of covariate effects without losing the mathematical simplicity of Cox PH model. In the present work, we examined the Cox PH and Gray PC-TVC models on the posttransplant survival analysis of 288 pediatric liver transplant patients diagnosed with cancer. We obtained potential predictors through univariable (P < 0.15) and multivariable models with forward selection (P < 0.05) for the Cox PH and Gray PC-TVC models, which coincide. While the Cox PH model provided reasonable average results in estimating covariate effects on posttransplant survival, the Gray model using piecewise constant penalized splines showed more details of how those effects change over time. PMID:23762197

  10. Post liver transplantation lymphoproliferative disorder mimics recurrence of hepatocellular carcinoma.

    PubMed

    Poovorawan, Kittiyod; Linlawan, Sittikorn; Wisedopas, Naruemon; Komolmit, Piyawat

    2013-01-01

    We report a case of Epstein-Barr virus (EBV)-related postliver transplantation lymphoproliferative disorder (PTLD) in a patient with post liver transplant which initially presented in a CT scan image mimicking recurrence of hepatocellular carcinoma. Histopathology showed atypical plasma cell-like infiltration, and immunohistochemistry confirmed diagnosis of EBV-associated diffuse large B-cell lymphoma. Typical imaging from dynamic phases contrast CT scan might not accurately diagnose recurrent HCC in postorthotropic liver transplantation. Liver biopsy should be performed for accurate diagnosis and proper treatment. PMID:24351512

  11. Single-dose pegfilgrastim is comparable to daily filgrastim in mobilizing peripheral blood stem cells: a case-matched study in patients with lymphoproliferative malignancies

    Microsoft Academic Search

    Mervi Putkonen; Auvo Rauhala; Tarja-Terttu Pelliniemi; Kari Remes

    2009-01-01

    Pegfilgrastim (PEGFIL) has been found to be comparable to daily filgrastim (FIL) in managing chemotherapy-induced neutropenia.\\u000a In the present study, we evaluated the ability of PEGFIL to mobilize stem cells in 38 consecutive patients with lymphoproliferative\\u000a diseases (multiple myeloma, n?=?18; lymphomas, n?=?15; chronic lymphocytic leukemia, n?=?5). Patients were mobilized using PEGFIL (6–18 mg as a single dose) during 2005–2006; 32 then

  12. Quaternary epitopes of ?345(IV) collagen initiate Alport post-transplant anti-GBM nephritis.

    PubMed

    Olaru, Florina; Luo, Wentian; Wang, Xu-Ping; Ge, Linna; Hertz, Jens Michael; Kashtan, Clifford E; Sado, Yoshikazu; Segal, Yoav; Hudson, Billy G; Borza, Dorin-Bogdan

    2013-05-01

    Alport post-transplant nephritis (APTN) is an aggressive form of anti-glomerular basement membrane disease that targets the allograft in transplanted patients with X-linked Alport syndrome. Alloantibodies develop against the NC1 domain of ?5(IV) collagen, which occurs in normal kidneys, including renal allografts, forming distinct ?345(IV) and ?1256(IV) networks. Here, we studied the roles of these networks as antigens inciting alloimmunity and as targets of nephritogenic alloantibodies in APTN. We found that patients with APTN, but not those without nephritis, produce two kinds of alloantibodies against allogeneic collagen IV. Some alloantibodies targeted alloepitopes within ?5NC1 monomers, shared by ?345NC1 and ?1256NC1 hexamers. Other alloantibodies specifically targeted alloepitopes that depended on the quaternary structure of ?345NC1 hexamers. In Col4a5-null mice, immunization with native forms of allogeneic collagen IV exclusively elicited antibodies to quaternary ?345NC1 alloepitopes, whereas alloimmunogens lacking native quaternary structure elicited antibodies to shared ?5NC1 alloepitopes. These results imply that quaternary epitopes within ?345NC1 hexamers may initiate alloimmune responses after transplant in X-linked Alport patients. Thus, ?345NC1 hexamers are the culprit alloantigen and primary target of all alloantibodies mediating APTN, whereas ?1256NC1 hexamers become secondary targets of anti-?5NC1 alloantibodies. Reliable detection of alloantibodies by immunoassays using ?345NC1 hexamers may improve outcomes by facilitating early, accurate diagnosis. PMID:23620401

  13. Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders

    PubMed Central

    MUŃOZ, Ana; RIBER, Cristina; TRIGO, Pablo; CASTEJÓN, Francisco

    2010-01-01

    Leukemia, i.e., the neoplasia of one or more cell lines of the bone marrow, although less common than in other species, it is also reported in horses. Leukemia can be classified according to the affected cells (myeloproliferative or lymphoproliferative disorders), evolution of clinical signs (acute or chronic) and the presence or lack of abnormal cells in peripheral blood (leukemic, subleukemic and aleukemic leukemia). The main myeloproliferative disorders in horses are malignant histiocytosis and myeloid leukemia, the latter being classified as monocytic and myelomonocytic, granulocytic, primary erythrocytosis or polycythemia vera and megakaryocytic leukemia. The most common lymphoproliferative disorders in horses are lymphoid leukemia, plasma cell or multiple myeloma and lymphoma. Lymphoma is the most common hematopoietic neoplasia in horses and usually involves lymphoid organs, without leukemia, although bone marrow may be affected after metastasis. Lymphoma could be classified according to the organs involved and four main clinical categories have been established: generalized-multicentric, alimentary-gastrointestinal, mediastinal-thymic-thoracic and cutaneous. The clinical signs, hematological and clinical pathological findings, results of bone marrow aspirates, involvement of other organs, prognosis and treatment, if applicable, are presented for each type of neoplasia. This paper aims to provide a guide for equine practitioners when approaching to clinical cases with suspicion of hematopoietic neoplasia. PMID:24833969

  14. Anticipation in Families with Chronic Lymphocytic Leukemia and Other Lymphoproliferative Disorders

    PubMed Central

    Awan, Haneef; Jřnsson, Viggo; Johannesen, Tom B.; Ly, Bernt; Tjřnnfjord, Geir E.

    2010-01-01

    Fifty-one parent-offspring pairs with chronic lymphocytic leukemia (CLL) or other lymphoproliferative disorders (nonCLL) such as malignant lymphoma, multiple myeloma, or other types of lymphocytic leukemia than CLL were ascertained independently in 38 families. There were 30 CLL-CLL parent-offspring pairs and 21 pairs with nonCLL in parents and/or in offspring. The median age of onset of disease was 13 years lower in the offspring than in the parents when comparing all 51 pairs (P < 0.001). This difference was mainly caused by a significantly lower age at onset in offspring with parental nonCLL (P < 0.001) where paternal disease was transferred especially to sons, while affected offspring to parents with CLL have the same age at debut of disease than their parents (P = 0.130) and a nearly equal transfer to sons and daughters. The low-malignant follicular small B-cell lymphoma was the predominant diagnosis within nonCLL. Anticipation is pointed out as one likely mechanism behind the lower age at onset of disease in offspring than in parents, even if a part of this difference is ascribed to a generally earlier diagnosis with modern technology in offspring than in parents. PMID:21566766

  15. AUTOLOGOUS LYMPHOKINE-ACTIVATED KILLER CELL THERAPY OF EPSTEIN-BARR VIRUS-POSITIVE AND -NEGATIVE LYMPHOPROLIFERATIVE DISORDERS ARISING IN ORGAN TRANSPLANT RECIPIENTS1

    PubMed Central

    Nalesnik, Michael A.; Rao, Abdul S.; Furukawa, Hiro; Pham, Si; Zeevi, Adriana; Fung, John J.; Klein, George; Gritsch, H. Albin; Elder, Elaine; Whiteside, Theresa L.; Starzl, Thomas E.

    2010-01-01

    Lymphoreticular malignancies, collectively called posttransplant lymphoproliferative disorders (PTLD), eventually develop in 2–5% of organ transplant recipients. They frequently undergo regression when immunosuppression is reduced or stopped. This feature has been associated with a previous or de novo Epstein-Barr virus (EBV) infection. We herein describe immunotherapy with autologous lymphokine-activated killer (LAK) cells in seven patients with PTLD (four EBV-positive patients and three EBV-negative patients). Autologous peripheral blood mononuclear cells were obtained by leukapheresis, depleted of monocytes, and cultured in the presence of interleukin 2 for 10 to 11 days. A single dose of 5.2 × 109 to 5.6 × 1010 LAK cells was given intravenously. Systemic interleukin 2 was not administered. The four patients with EBV+ PTLD had complete tumor regression; two of them developed controllable rejection. Three patients are well 13–16 months after treatment; the fourth patient died of pneumonia 41 days after infusion. Three patients with EBV? lymphomas had no response despite prior evidence that their tumors also were subject to immune surveillance. Two of these three patients died after being given other treatment, and the third patient has persistent tumor. In conclusion, autologous LAK cell infusion was effective for treatment of four EBV+ organ transplant recipients. LAK cell efficacy for three patients with EBV? PTLD was not evaluable under the management circumstances in which this treatment was utilized. PMID:9142315

  16. Filgrastim, lenograstim and pegfilgrastim in the mobilization of peripheral blood progenitor cells in patients with lymphoproliferative malignancies.

    PubMed

    Ria, Roberto; Reale, Antonia; Melaccio, Assunta; Racanelli, Vito; Dammacco, Franco; Vacca, Angelo

    2015-05-01

    Patients with lymphoproliferative disorders, candidate to autologous stem cell transplantation (ASCT), require mobilization with chemotherapy and granulocyte colony -stimulating factor (G-CSF). This study looked for differences in hematopoietic peripheral stem cells (HPSCs) mobilization in response to the three available G-CSFs, namely lenograstim, filgrastim, and pegfilgrastim. Between 2000 and 2012, 146 patients (66 M and 80 F) who underwent ASCT for multiple myeloma, non-Hodgkin's lymphoma or Hodgkin's lymphoma were studied. All patients received induction therapy and then a mobilization regimen with cyclophosphamide plus lenograstim, or filgrastim, or pegfilgrastim. From days 12 to 14, HPSCs were collected by two to three daily leukaphereses. Our results show that high-dose cyclophosphamide plus lenograstim achieved adequate mobilization and the collection target more quickly and with fewer leukaphereses as compared to filgrastim and pegfilgrastim. No differences between the three regimens were observed regarding toxicity and days to WBC and platelet recovery. Thus, lenograstim may represent the ideal G-CSF for PBSC mobilization in patients with lymphoproliferative diseases. Further studies are needed to confirm these results and better understand the biological bases of these differences. PMID:24722996

  17. Detection of BRAF mutations in patients with hairy cell leukemia and related lymphoproliferative disorders.

    PubMed

    Blombery, Piers A; Wong, Stephen Q; Hewitt, Chelsee A; Dobrovic, Alexander; Maxwell, Ellen L; Juneja, Surender; Grigoriadis, George; Westerman, David A

    2012-05-01

    Hairy cell leukemia has been shown to be strongly associated with the BRAF V600E mutation. We screened 59 unenriched archived bone marrow aspirate and peripheral blood samples from 51 patients with hairy cell leukemia using high resolution melting analysis and confirmatory Sanger sequencing. The BRAF V600E mutation was detected in 38 samples (from 36 patients). The BRAF V600E mutation was detected in all samples with disease involvement above the limit of sensitivity of the techniques used. Thirty-three of 34 samples from other hematologic malignancies were negative for BRAF mutations. A BRAF K601E mutation was detected in a patient with splenic marginal zone lymphoma. Our data support the recent finding of a disease defining point mutation in hairy cell leukemia. Furthermore, high resolution melting with confirmatory Sanger sequencing are useful methods that can be employed in routine diagnostic laboratories to detect BRAF mutations in patients with hairy cell leukemia and related lymphoproliferative disorders. PMID:22133769

  18. Detection of BRAF mutations in patients with hairy cell leukemia and related lymphoproliferative disorders

    PubMed Central

    Blombery, Piers A.; Wong, Stephen Q.; Hewitt, Chelsee A.; Dobrovic, Alexander; Maxwell, Ellen L.; Juneja, Surender; Grigoriadis, George; Westerman, David A.

    2012-01-01

    Hairy cell leukemia has been shown to be strongly associated with the BRAF V600E mutation. We screened 59 unenriched archived bone marrow aspirate and peripheral blood samples from 51 patients with hairy cell leukemia using high resolution melting analysis and confirmatory Sanger sequencing. The BRAF V600E mutation was detected in 38 samples (from 36 patients). The BRAF V600E mutation was detected in all samples with disease involvement above the limit of sensitivity of the techniques used. Thirty-three of 34 samples from other hematologic malignancies were negative for BRAF mutations. A BRAF K601E mutation was detected in a patient with splenic marginal zone lymphoma. Our data support the recent finding of a disease defining point mutation in hairy cell leukemia. Furthermore, high resolution melting with confirmatory Sanger sequencing are useful methods that can be employed in routine diagnostic laboratories to detect BRAF mutations in patients with hairy cell leukemia and related lymphoproliferative disorders. PMID:22133769

  19. Associations of pretransplant serum albumin with post-transplant outcomes in kidney transplant recipients.

    PubMed

    Molnar, M Z; Kovesdy, C P; Bunnapradist, S; Streja, E; Mehrotra, R; Krishnan, M; Nissenson, A R; Kalantar-Zadeh, K

    2011-05-01

    The association between pretransplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48 ± 13 years old and included 37% women and 27% diabetics. The higher pretransplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pretransplant serum albumin concentration was associated with 13% lower all-cause mortality (HR = 0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR = 0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR = 0.93[0.89-0.97]) and 4% lower DGF risk (OR = 0.96[0.93-0.99]). Hence, lower pretransplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-waitlisted hemodialysis patients and their impacts on post-transplant outcomes are indicated. PMID:21449945

  20. Extra-intestinal malignancies in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (III).

    PubMed

    Magro, Fernando; Peyrin-Biroulet, Laurent; Sokol, Harry; Aldeger, Xavier; Costa, Antonia; Higgins, Peter D; Joyce, Joel C; Katsanos, Konstantinos H; Lopez, Anthony; de Xaxars, Teresa Mas; Toader, Elena; Beaugerie, Laurent

    2014-01-01

    The incidence of lymphoproliferative disorders (LD) is increasing in developed countries. Patients with inflammatory bowel disease (IBD) exposed to thiopurines are at additional risk of three specific forms of LD: Epstein-Barr-Virus-related post-transplant like LD, hepato-splenic T-cell lymphoma and post-mononucleosis lymphoproliferation. The risk of the two latter forms of LD can be reduced when considering specific immunosuppressive strategies in young males. It is still unclear whether the risk of uterine cervix abnormalities is increased in IBD women, irrespective of the use of immunosuppressants. Given the excess risk demonstrated in various other contexts of immunosuppression, it is currently recommended that all women with IBD, particularly those receiving immunosuppressants, strictly adhere to a screening program of cervical surveillance and undergo vaccination against HPV, when appropriate. Patients with IBD receiving immunosuppressants are at increased risk of skin cancers. The risk of non-melanoma skin cancer is notably increased in patients receiving thiopurines. Recent data suggest that the risk of melanoma is mildly increased in patients exposed to anti-TNF therapy. All IBD patients should adhere to a program of sun protection and dermatological surveillance, whose details should take into account the other non-IBD-related risk factors. PMID:23721759

  1. Epstein-Barr virus-associated lymphoproliferative disorders.

    PubMed

    Grywalska, Ewelina; Markowicz, Justyna; Grabarczyk, Piotr; Pasiarski, Marcin; Roli?ski, Jacek

    2013-01-01

    The Epstein-Barr virus (EBV) is one of the most common human viruses, infecting more than 90% of the world's adult population. In some individuals the interplay between EBV replication, latency and immune control can be disrupted and evokes prolonged proliferation of EBV-infected lymphocytes and their malignant transformation. Since its discovery as the first human tumor virus, EBV has been implicated in the development of a wide range of human cancers. The evidence for an association with EBV is the strongest for Burkitt's lymphoma, NK/T cell lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma and for malignant lymphomas in immune incompetent patients. Additionally, certain epithelial cell tumors, such as gastric carcinoma and breast carcinoma, have been defined as EBV related. However, the virus may be encountered in other types of malignancies. The oncogenic potential of EBV is related to its ability to infect and transform B lymphocytes into continuously growing lymphoblastoid cell lines. EBV encodes a series of products mimicking several growth, transcription and anti-apoptotic factors, to usurp control of the pathways that regulate diverse homeostatic cellular functions. However, the exact mechanism by which EBV promotes oncogenesis remains unclear. The focus of this review is to summarize the current knowledge of oncogenic potential of the Epstein-Barr virus and its role in the pathogenesis of EBV-associated lymphoproliferative disorders. PMID:23752600

  2. Primary Cutaneous Gamma-Delta T-Cell Lymphoproliferative Disorder in a 3-Year-Old Boy.

    PubMed

    Soon, Christopher W M; Link, Michael; Kim, Youn H; Kim, Jinah

    2015-07-01

    Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a rare disorder, constituting less than 1% of primary cutaneous lymphomas. Most cases occur in adults and may present as plaques or nodules with ulceration. Here we describe an unusual case of PCGD-TCL in a 3-year-old boy who presented with asymptomatic subcutaneous nodules. To our knowledge, this report represents one of the youngest reported patients with gamma-delta lymphoma/lymphoproliferative disorder. In addition, our patient has an indolent clinical presentation with greater than 1 year clinical follow-up. Because gamma-delta T-cell lymphomas are exceedingly rare in children, we acknowledge that the clinical course/outcome in young patients is still unclear. We hope to add to the recognition that PCGD-TCLs demonstrate a wide clinical spectrum of disease with relatively indolent presentations in some cases. PMID:25072685

  3. Interleukin-12 stimulation of lymphoproliferative responses in Trypanosoma cruzi infection

    PubMed Central

    Galvăo da Silva, Ana Paula; de Almeida Abrahamsohn, Ises

    2001-01-01

    The cytokine interleukin-12 (IL-12) is essential for resistance to Trypanosoma cruzi infection because it stimulates the synthesis of interferon-? (IFN-?), a major activator of the parasiticidal effect of macrophages. A less studied property of IL-12 is its ability to amplify the proliferation of T or natural killer (NK) lymphocytes. We investigated the role of endogenously produced IL-12 in the maintenance of parasite antigen (T-Ag)-specific lymphoproliferative responses during the acute phase of T. cruzi infection. We also studied whether treatment with recombinant IL-12 (rIL-12) would stimulate T-Ag-specific or concanavalin A (Con A)-stimulated lymphoproliferation and abrogate the suppression that is characteristic of the acute phase of infection. Production of IL-12 by spleen-cell cultures during T. cruzi infection increased in the first days of infection (days 3–5) and decreased as infection progressed beyond day 7. The growth-promoting activity of endogenous IL-12 on T-Ag-specific proliferation was observed on day 5 of infection. Treatment of cultures with rIL-12 promoted a significant increase in Con A-stimulated proliferation by spleen cells from normal or infected mice. Enhanced T-Ag-specific proliferation by rIL-12 was seen in spleen cell cultures from infected mice providing that nitric oxide production was inhibited by treatment with the competitive inhibitor NG-monomethyl-l-arginine (NMMA). Enhancement of proliferation promoted by IL-12 occurred in the presence of neutralizing anti-interleukin-2 (IL-2) antibody, suggesting that this activity of IL-12 was partly independent of endogenous IL-2. Thymidine incorporation levels achieved with rIL-12 treatment of the cultures were ? 50% of those stimulated by rIL-2 in the same cultures. PMID:11722650

  4. Haploidentical BMT and post-transplant Cy for severe aplastic anemia: a multicenter retrospective study.

    PubMed

    Esteves, I; Bonfim, C; Pasquini, R; Funke, V; Pereira, N F; Rocha, V; Novis, Y; Arrais, C; Colturato, V; de Souza, M P; Torres, M; Fernandes, J F; Kerbauy, F R; Ribeiro, A A F; Santos, F P S; Hamerschlak, N

    2015-05-01

    Patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor need new therapeutic approaches. Hematopoietic SCT (HSCT) using mismatched or haploidentical related donors has been used in the past, but was associated with a significant risk of GVHD and mortality. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but the majority of reports have focused on patients with hematology malignancies. We describe the outcome of 16 patients who underwent haploidentical transplantation using a reduced-intensity conditioning regimen with post-transplant Cy. Stem cell sources were BM (N=13) or PBSCs (N=3). The rate of neutrophil engraftment was 94% and of platelet engraftment was 75%. Two patients had secondary graft failure and were successfully salvaged with another transplant. Three patients developed acute GVHD being grades 2-4 in two. Five patients have died and the 1-year OS was 67.1% (95% confidence interval: 36.5-86.4%). In our small series, the use of a reduced-intensity conditioning with post-transplant Cy in haploidentical BMT was associated with high rates of engraftment and low risk of GVHD in patients with relapsed/refractory SAA. PMID:25730184

  5. EBV-driven B-cell lymphoproliferative disorders: from biology, classification and differential diagnosis to clinical management.

    PubMed

    Ok, Chi Young; Li, Ling; Young, Ken H

    2015-01-01

    Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting >90% of the adult population. EBV targets B-lymphocytes and achieves latent infection in a circular episomal form. Different latency patterns are recognized based on latent gene expression pattern. Latent membrane protein-1 (LMP-1) mimics CD40 and, when self-aggregated, provides a proliferation signal via activating the nuclear factor-kappa B, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase pathways to promote cellular proliferation. LMP-1 also induces BCL-2 to escape from apoptosis and gives a signal for cell cycle progression by enhancing cyclin-dependent kinase 2 and phosphorylation of retinoblastoma (Rb) protein and by inhibiting p16 and p27. LMP-2A blocks the surface immunoglobulin-mediated lytic cycle reactivation. It also activates the Ras/PI3K/Akt pathway and induces Bcl-xL expression to promote B-cell survival. Recent studies have shown that ebv-microRNAs can provide extra signals for cellular proliferation, cell cycle progression and anti-apoptosis. EBV is well known for association with various types of B-lymphocyte, T-lymphocyte, epithelial cell and mesenchymal cell neoplasms. B-cell lymphoproliferative disorders encompass a broad spectrum of diseases, from benign to malignant. Here we review our current understanding of EBV-induced lymphomagenesis and focus on biology, diagnosis and management of EBV-associated B-cell lymphoproliferative disorders. PMID:25613729

  6. Posttransplant Complex Inferior Venacava Balloon Dilatation After Hepatic Vein Stenting

    SciTech Connect

    Kohli, Vikas, E-mail: vkohli_md@yahoo.co [Indraprastha Apollo Hospital, Pediatric Cardiology and Congenital Cardiac Surgery Unit (India); Wadhawan, Manav [Indraprastha Apollo Hospital, Department of Gastroenterology and Hepatology (India); Gupta, Subhash [Indraprastha Apollo Hospital, Department of Liver Transplant (India); Roy, Vipul [Indraprastha Apollo Hospital, Department of Cardiology (India)

    2010-02-15

    Orthotopic and living related liver transplantation is an established mode of treatment of end-stage liver disease. One of the major causes of postoperative complications is vascular anastomotic stenosis. One such set of such complications relates to hepatic vein, inferior vena cava (IVC), or portal vein stenosis, with a reported incidence of 1-3%. The incidence of vascular complications is reported to be higher in living donor versus cadaveric liver transplants. We encountered a patient with hepatic venous outflow tract obstruction, where the hepatic vein had been previously stented, but the patient continued to have symptoms due to additional IVC obstruction. The patient required double-balloon dilatation of the IVC simultaneously from the internal jugular vein and IVC.

  7. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia

    PubMed Central

    Jerez, Andres; Clemente, Michael J.; Makishima, Hideki; Koskela, Hanna; LeBlanc, Francis; Peng Ng, Kwok; Olson, Thomas; Przychodzen, Bartlomiej; Afable, Manuel; Gomez-Segui, Ines; Guinta, Kathryn; Durkin, Lisa; Hsi, Eric D.; McGraw, Kathy; Zhang, Dan; Wlodarski, Marcin W.; Porkka, Kimmo; Sekeres, Mikkael A.; List, Alan; Mustjoki, Satu; Loughran, Thomas P.

    2012-01-01

    Chronic lymphoproliferative disorders of natural killer cells (CLPD-NKs) and T-cell large granular lymphocytic leukemias (T-LGLs) are clonal lymphoproliferations arising from either natural killer cells or cytotoxic T lymphocytes (CTLs). We have investigated for distribution and functional significance of mutations in 50 CLPD-NKs and 120 T-LGL patients by direct sequencing, allele-specific PCR, and microarray analysis. STAT3 gene mutations are present in both T and NK diseases: approximately one-third of patients with each type of disorder convey these mutations. Mutations were found in exons 21 and 20, encoding the Src homology 2 domain. Patients with mutations are characterized by symptomatic disease (75%), history of multiple treatments, and a specific pattern of STAT3 activation and gene deregulation, including increased expression of genes activated by STAT3. Many of these features are also found in patients with wild-type STAT3, indicating that other mechanisms of STAT3 activation can be operative in these chronic lymphoproliferative disorders. Treatment with STAT3 inhibitors, both in wild-type and mutant cases, resulted in accelerated apoptosis. STAT3 mutations are frequent in large granular lymphocytes suggesting a similar molecular dysregulation in malignant chronic expansions of NK and CTL origin. STAT3 mutations may distinguish truly malignant lymphoproliferations involving T and NK cells from reactive expansions. PMID:22859607

  8. Immunophenotypic characterization of acute leukemias and chronic lymphoproliferative disorders: practical recommendations and classifications

    Microsoft Academic Search

    R. Garand; N. Robillard

    1997-01-01

    Immunophenotypic characterization of leukemic cells has become essential for the diagnosis of acute leukemias (AL) and chronic lymphoproliferative disorders (CLPD). Immunophenotyping allows to classify AL according to (i) lineage assignement of the leukemic clone based on the degree of specificity (or “score”) of expressed markers, (ii) the différentiation level of the clone and (iii) the presence of irrelevant markers. In

  9. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome

    Microsoft Academic Search

    Stéphanie Rigaud; Marie-Claude Fondančche; Nathalie Lambert; Benoit Pasquier; Véronique Mateo; Pauline Soulas; Lionel Galicier; Françoise Le Deist; Frédéric Rieux-Laucat; Patrick Revy; Alain Fischer; Genevičve de Saint Basile; Sylvain Latour

    2006-01-01

    The homeostasis of the immune response requires tight regulation of the proliferation and apoptosis of activated lymphocytes. In humans, defects in immune homeostasis result in lymphoproliferation disorders including autoimmunity, haemophagocytic lymphohystiocytosis and lymphomas. The X-linked lymphoproliferative syndrome (XLP) is a rare, inherited immunodeficiency that is characterized by lymphohystiocytosis, hypogammaglobulinaemia and lymphomas, and that usually develops in response to infection with

  10. Research update: Avian Disease and Oncology Laboratory avian tumor viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomics and Immunogenetics Use of genomics to identify QTL, genes, and proteins associated with resistance to Marek’s disease. Marek’s disease (MD), a lymphoproliferative disease caused by the highly oncogenic herpesvirus Marek's disease virus (MDV), continues to be a major disease concern to the p...

  11. Host and donor immune responses contribute to antiviral effects of amotosalen-treated donor lymphocytes following early posttransplant cytomegalovirus infection.

    PubMed

    Hossain, Mohammad S; Roback, John D; Wang, Fengrong; Waller, Edmund K

    2008-05-15

    We have previously shown that amotosalen-treated splenocytes rescued allorecipients from a lethal dose of mouse CMV (MCMV) administered on day 0 in experimental parent C57BL/6-->CB6F1 allogeneic bone marrow transplant. In this study, we investigated the mechanism of antiviral activity of amotosalen-treated donor splenocytes when sublethal MCMV infections were administered 7 days posttransplant. Recipients of 3 x 10(6) untreated splenocytes were used as control. Following MCMV infection, recipients of untreated splenocytes had 40% early mortality due to acute graft-vs-host disease compared with no deaths among recipients of 10 x 10(6) treated splenocytes. However, recipients of both types of donor splenocytes effectively cleared MCMV from their liver. Like the untreated CD8(+) T cells, amotosalen-treated CD8(+) T cells equally retained their in vivo CTL activity against MCMV early peptide-pulsed targets and expressed similar levels of granzyme B within 11 days of infection. In contrast to full donor chimerism in recipients of untreated splenocytes, recipients of amotosalen-treated splenocytes showed mixed chimerism with both donor spleen- and host-derived anti-MCMV CD8(+) T cells in their blood and lymphoid organs, with significantly higher numbers of host-derived CD4(-)CD8(-) (double negative) T cells in the spleens of recipients of treated splenocytes compared with the recipients of untreated splenocytes. Additionally, recipients of amotosalen-treated splenocytes had lower levels of serum IFN-gamma and TNF-alpha in response to MCMV infection compared with untreated recipients. Thus, adoptive immunotherapy with treated T cells is a novel therapeutic approach that facilitates hematopoietic engraftment and permits antiviral immunity of both donor and host T cells without graft-vs-host disease. PMID:18453610

  12. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update.

    PubMed

    Bacigalupo, A; Dominietto, A; Ghiso, A; Di Grazia, C; Lamparelli, T; Gualandi, F; Bregante, S; Van Lint, M T; Geroldi, S; Luchetti, S; Grasso, R; Pozzi, S; Colombo, N; Tedone, E; Varaldo, R; Raiola, A M

    2015-06-01

    This is a report of 148 patients with hematologic malignancies who received an unmanipulated haploidentical bone marrow transplant (BMT), followed by post-transplant high-dose cyclophosphamide (PT-CY). All patients received a myeloablative conditioning consisting of thiotepa, busulfan, fludarabine (n=92) or TBI, fludarabine (n=56). The median age was 47 years (17-74); 47 patients were in first remission (CR1), 37 in second remission (CR2) and 64 had an active disease; all patients were first grafts. The diagnosis was acute leukemia (n=75), myelodisplastic syndrome (n=24), myelofibrosis (n=16), high-grade lytmphoma (n=15) and others (n=18). GVHD prophylaxis consisted in PT-CY on days +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). The median day for neutrophil engraftment was day +18 (13-32). The cumulative incidence of grades II-IV acute GVHD was 24%, and of grades III-IV GVHD 10%. The incidence of moderate-severe chronic GVHD was 12%. With a median follow-up for the surviving patients of 313 days (100-1162), the cumulative incidence of transplant-related mortality (TRM) is 13%, and the relapse-related death is 23%. The actuarial 22 months overall survival is 77% for CR1 patients, 49% for CR2 patients and 38% for patients grafted in relapse (P<0.001). Major causes of death were relapse (22%), GVHD (2%) and infections (6%). We confirm our initial results, suggesting that a myeloablative conditioning regimen followed by unmanipulated haploidentical BMT with PT-CY, results in a low risk of acute and chronic GVHD and encouraging rates of TRM and overall survival, also for patients with active disease at the time of transplant. PMID:26039205

  13. Waldenström's macroglobulinemia harbors a unique proteome where Ku70 is severely underexpressed as compared with other B-lymphoproliferative disorders.

    PubMed

    Perrot, A; Pionneau, C; Azar, N; Baillou, C; Lemoine, F M; Leblond, V; Merle-Béral, H; Béné, M-C; Herbrecht, R; Bahram, S; Vallat, L

    2012-01-01

    Waldenström's macroglobulinemia (WM) is a clonal B-cell lymphoproliferative disorder (LPD) of post-germinal center nature. Despite the fact that the precise molecular pathway(s) leading to WM remain(s) to be elucidated, a hallmark of the disease is the absence of the immunoglobulin heavy chain class switch recombination. Using two-dimensional gel electrophoresis, we compared proteomic profiles of WM cells with that of other LPDs. We were able to demonstrate that WM constitutes a unique proteomic entity as compared with chronic lymphocytic leukemia and marginal zone lymphoma. Statistical comparisons of protein expression levels revealed that a few proteins are distinctly expressed in WM in comparison with other LPDs. In particular we observed a major downregulation of the double strand repair protein Ku70 (XRCC6); confirmed at both the protein and RNA levels in an independent cohort of patients. Hence, we define a distinctive proteomic profile for WM where the downregulation of Ku70-a component of the non homologous end-joining pathway-might be relevant in disease pathophysiology. PMID:22961060

  14. Marek's disease virus induced transient paralysis--a closer look

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s Disease (MD) is a lymphoproliferative disease of domestic chickens caused by a highly cell-associated alpha herpesvirus, Marek’s disease virus (MDV). Clinical signs of MD include depression, crippling, weight loss, and transient paralysis (TP). TP is a disease of the central nervous system...

  15. Research update: Avian Disease and Oncology Laboratory avian tumor viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomics and Immunogenetics Marek’s disease (MD), a lymphoproliferative disease caused by the highly oncogenic herpesvirus Marek's disease virus (MDV), continues to be a major disease concern to the poultry industry. The fear of MD is further enhanced by unpredictable vaccine breaks that result in ...

  16. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab.

    PubMed

    Schlegel, Patrick; Lang, Peter; Zugmaier, Gerhard; Ebinger, Martin; Kreyenberg, Hermann; Witte, Kai-Erik; Feucht, Judith; Pfeiffer, Matthias; Teltschik, Heiko-Manuel; Kyzirakos, Christina; Feuchtinger, Tobias; Handgretinger, Rupert

    2014-07-01

    We report on posttransplant relapsed pediatric patients with B-precursor acute lymphoblastic leukemia with no further standard of care therapy who were treated with the T-cell engaging CD19/CD3-bispecific single-chain antibody construct blinatumomab on a compassionate use basis. Blast load was assessed prior to, during and after blinatumomab cycle using flow cytometry to detect minimal residual disease, quantitative polymerase chain reaction for rearrangements of the immunoglobulin or T-cell receptor genes, and bcr/abl mutation detection in one patient with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blinatumomab was administered as a 4-week continuous intravenous infusion at a dosage of 5 or 15 ?g/m(2)/day. Nine patients received a total of 18 cycles. Four patients achieved complete remission after the first cycle of treatment; 2 patients showed a complete remission from the second cycle after previous reduction of blast load by chemotherapy. Three patients did not respond, of whom one patient proceeded to a second cycle without additional chemotherapy and again did not respond. Four patients were successfully retransplanted in molecular remission from haploidentical donors. After a median follow up of 398 days, the probability of hematologic event-free survival is 30%. Major toxicities were grade 3 seizures in one patient and grade 3 cytokine release syndrome in 2 patients. Blinatumomab can induce molecular remission in pediatric patients with posttransplant relapsed B-precursor acute lymphoblastic leukemia and facilitate subsequent allogeneic hematopoietic stem cell transplantation from haploidentical donor with subsequent long-term leukemia-free survival. PMID:24727818

  17. Multiple Clinical Presentations of Lymphoproliferative Disorders in Pediatric Liver Transplant Recipients: A Single-Center Experience

    Microsoft Academic Search

    M. L. Pinho-Apezzato; U. Tannuri; A. C. A. Tannuri; E. S. Mello; F. Lima; N. E. Gibelli; M. M. Santos; A. A. Ayoub; J. G. Maksoud-Filho; M. C. Velhote; M. M. Silva; W. C. Andrade; H. T. Miyatani

    2010-01-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation that has been linked to Epstein-Barr virus (EBV) infection. The aim of this article was to describe a single-center experience with the multiplicity of clinical presentations of PTLD. Among 350 liver transplantations performed in 303 children, 13 survivor children displayed a histological diagnosis of PTLD (13\\/242 survivors; 5.4%).

  18. Age-related EBV-associated lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma

    PubMed Central

    Dojcinov, Stefan D.; Venkataraman, Girish; Pittaluga, Stefania; Wlodarska, Iwona; Schrager, Jeffrey A.; Raffeld, Mark; Hills, Robert K.

    2011-01-01

    We investigated age-related EBV+ B-cell lymphoproliferations in the Western population. The clinical features, histology, immunophenotype, EBV-encoded RNA in situ hybridization, and clonality by PCR of T-cell receptor gamma and immunoglobulin genes were categorized in 122 EBV+ lesions as follows: (1) reactive lymphoid hyperplasia; (2) polymorphic extranodal or (3) polymorphic nodal lymphoproliferative disease (LPD); and (4) diffuse large B-cell lymphoma (DLBCL). Interphase FISH for IG and PAX5 gene rearrangements was performed on 17 cases of DLBCL. The overall median age was 75 years (range, 45-101 years; 67 men, 55 women), and 67, 79, 73, and 77 years, respectively, for groups 1 through 4. Sixteen of 21 cases of polymorphic extranodal LPD were classified as EBV+ mucocutaneous ulcer. PCR for immunoglobulin genes was polyclonal in reactive lymphoid hyperplasia (84%) and monoclonal in 33%, 63%, and 56% of polymorphic extranodal and nodal LPD cases and DLBCL, respectively. All groups showed restricted/clonal T-cell receptor responses (27%-70%). By FISH, 19% of DLBCLs showed IGH@ rearrangements, but PAX5 was unaffected. Disease-specific 5-year survival was 100%, 93%, 57%, and 25% for groups 1-4, respectively, and 100% for patients with EBV+ mucocutaneous ulcer. Disease volume was predictive of therapy response (P = .0002), and pathologic subtype was predictive of overall outcome (P = .001). Age-related EBV+ B-cell LPD encompasses a wider disease spectrum than previously recognized and includes both reactive and neoplastic conditions. Reduction in the T-cell repertoire may contribute to decreased immune surveillance. PMID:21385849

  19. Genetic bases for Marek's disease resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek's disease (MD) is a highly contagious lymphoproliferative disease of chickens caused by MD virus (MDV). Therefore, the control of MD is of particular concern to the poultry industry. The poultry industry has been heavily relying on biosecurity and vaccination to control the spread and occurren...

  20. Immunophenotyping by flow cytometry of fine needle aspirates in the diagnosis of lymphoproliferative disorders: A retrospective study.

    PubMed

    Henrique, R M; Sousa, M E; Godinho, M I; Costa, I; Barbosa, I L; Lopes, C A

    1999-01-01

    In order to determine the value of flow cytometric (FCM) immunophenotyping of fine-needle aspirates (FNA) in the diagnosis and classification of lymphoproliferative diseases, 61 tissue samples were studied and compared with the cytologic/histological results. In vivo and ex vivo FNA biopsy yielded the material for FCM, which comprised an extensive number of lymphoid cell markers. In all but three cases sufficient cells were collected. Overall, malignancy was diagnosed in 33 cases from a total of 47 (70.2%), and in the remaining cases malignancy was not detected. Eleven cases were correctly diagnosed as reactive processes (11/11). There were no false positive cases of malignancy, as diagnosed by FCM-FNA. The best accuracy was achieved in the low-grade B-cell lymphomas and lymphoblastic lymphoma/leukemia. We conclude that in a significant number of cases, FCM-FNA permits the separation between lymphoid malignancies and reactive processes without false positive results. It was found to be particularly useful in the differential diagnosis of mantle-cell and small-lymphocytic lymphoma and in the identification of lymphoblastic lymphoma/leukemia. PMID:10494131

  1. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop

    PubMed Central

    Bleesing, Jack J.; Dianzani, Umberto; Fleisher, Thomas A.; Jaffe, Elaine S.; Lenardo, Michael J.; Rieux-Laucat, Frederic; Siegel, Richard M.; Su, Helen C.; Teachey, David T.

    2010-01-01

    Lymphadenopathy in children for which no infectious or malignant cause can be ascertained constitutes a challenging diagnostic dilemma. Autoimmune lymphoproliferative syndrome (ALPS) is a human genetic disorder of lymphocyte apoptosis resulting in an accumulation of lymphocytes and childhood onset chronic lymphadenopathy, splenomegaly, multilineage cytopenias, and an increased risk of B-cell lymphoma. In 1999, investigators at the National Institutes of Health (NIH) suggested criteria to establish the diagnosis of ALPS. Since then, with approximately 500 patients with ALPS studied worldwide, significant advances in our understanding of the disease have prompted the need for revisions to the existing diagnostic criteria and classification scheme. The rationale and recommendations outlined here stem from an international workshop held at NIH on September 21 and 22, 2009, attended by investigators from the United States, Europe, and Australia engaged in clinical and basic science research on ALPS and related disorders. It is hoped that harmonizing the diagnosis and classification of ALPS will foster collaborative research and better understanding of the pathogenesis of autoimmune cytopenias and B-cell lymphomas. PMID:20538792

  2. A novel post-transplant alloantibody surveillance and intervention strategy that improves graft outcomes in sensitized renal transplant recipients.

    PubMed

    Kimball, Pamela M; King, Anne

    2011-01-01

    Chronic rejection, the leading cause of renal graft failure, is mediated by alloantibody graft destruction. Monitoring alloantibodies posttransplant might facilitate early diagnosis of alloantibody mediated graft destruction and provide an opportunity for intervention. Herein, we describe our alloantibody surveillance and intervention protocol that has improved graft survival. Patients (n = 69) with preoperatively positive FCXM and DSA were transplanted. Patient compatibility with donors was assessed by FCXM and donor specific antibody using single antigen bead Luminex. FCXM and DSA levels were monitored quarterly posttransplant. We identified a posttransplant profile strongly associated with chronic rejection. We then implemented a point-based formula that indicated when to initiate preemptive treatment with IVIG and plasmapheresis. The results of posttransplant antibody surveillance revealed 2 profiles. Most patients (65%) showed complete elimination of FCXM reactivity and DSA levels within 12 months of transplant. Three-year graft survival exceeded 95% and patients were chronic rejection-free. In contrast, the remaining patients failed to eliminate antibody as assessed by FCXM and DSA levels. Graft survival was inferior and chronic rejection was diagnosed in 43% of the group. Subsequent inclusion of preemptive treatment using the point-based system improved 3-year graft survival from 50% to 90%. In conclusion, the data show that implementation of an evidence based antibody surveillance protocol and an intervention protocol successfully improved graft survival. PMID:22755433

  3. Correlation between Marek’s disease virus pathotype and replication

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease virus (MDV) is an alphaherpesvirus that causes Marek’s disease (MD), a lymphoproliferative disease in chickens. Pathotyping has become an increasingly important assay for monitoring shifts in virulence of field strains, however, it is time-consuming and expensive and alternatives are...

  4. A COL4A3 gene mutation and post-transplant anti-?3(IV) collagen alloantibodies in Alport syndrome

    Microsoft Academic Search

    Raghu Kalluri; L. P. van den Heuvel; H. J. M. Smeets; C. H. Schroder; H. H. Lemmink; Ariel Boutaud; Eric G Neilson; Billy G Hudson

    1995-01-01

    A COL4A3 gene mutation and post-transplant anti-?3(IV) collagen alloantibodies in Alport syndrome. The X-linked Alport syndrome is associated with mutations and deletions in COL4A5 gene, one of six genes which constitute the ?-chains of type IV collagen in basement membranes. The autosomal recessive form of Alport syndrome is characterized by mutations and deletions in the COL4A3 and COL4A4 genes. A

  5. Post-transplant acute renal failure in cadaver renal recipients treated with cyclosporine.

    PubMed

    Hall, B M; Tiller, D J; Duggin, G G; Horvath, J S; Farnsworth, A; May, J; Johnson, J R; Sheil, A G

    1985-08-01

    The outcome of patients with acute renal failure following cadaveric renal transplant has been evaluated in a prospective, controlled trial, comparing treatment with cyclosporine (CSA) to prednisone, azathioprine, and antilymphocyte globulin (AZA). There was a high incidence of acute post-transplant renal failure in both groups: 37 of 51 CSA and 31 of 45 AZA patients, due to the long exposure of kidneys to warm and cold ischemia. Onset of adequate renal function was delayed for three or more weeks in 27 (53%) CSA and only nine (20%) AZA patients, and the only predisposing factor found was donor hypotension. All nine AZA and 18 of the 27 CSA patients with prolonged oliguria subsequently had a spontaneous diuresis. Nine of the CSA patients were changed to azathioprine and prednisone because of suspected CSA toxicity, and eight of these kidneys began functioning within days, even though they had been oliguric for 21 to 83 days. Of these nine patients, five had adequate long-term function on AZA, three developed CMV infections that were fatal to two individuals, and two rejected their grafts. Plasma CSA levels fluctuated widely in all patients, but were not higher in any group, including those with prolonged oliguria. During the oliguric period, biopsy specimens proved rejection was more common in the nine patients who had their CSA stopped than in the other CSA patients, and seven of these nine developed a diffuse interstitial fibrosis that was thought to be a manifestation of CSA toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3914572

  6. Dynamic equilibrium of Marek’s disease genomes during in vitro serial passage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by gallid herpesvirus type 2 (GaHV-2). The disease is controlled through mass vaccination with live-attenuated strains. Attenuation of oncogenic GaHV-2 involves the serial passage of a virulent field isolate in avian embryo fib...

  7. Unicentric Castleman's disease: an uncommon cause of posterior mediastinal mass

    PubMed Central

    Alavi, Aliasghar; Asadi Gharabaghi, Mehrnaz

    2013-01-01

    Castleman's disease is a rare lymphoproliferative disease that may be unicentric or multicentric in presentation. It may develop anywhere along with the lymphatic system such as the abdomen, neck and thoracic cavity. However, mediastinum is the most common location for unicentric disease. Here, we discuss a unicentric Castleman's disease in a 28-year-old woman who presented with cough, mild dysphagia and a large posterior mediastinal mass. PMID:23761562

  8. Eculizumab improves posttransplant thrombotic microangiopathy due to antiphospholipid syndrome recurrence but fails to prevent chronic vascular changes.

    PubMed

    Canaud, G; Kamar, N; Anglicheau, D; Esposito, L; Rabant, M; Noël, L-H; Guilbeau-Frugier, C; Sberro-Soussan, R; Del Bello, A; Martinez, F; Zuber, J; Rostaing, L; Legendre, C

    2013-08-01

    Thrombotic microangiopathy (TMA) is one of the hallmark vascular lesions of antiphospholipid syndrome nephropathy (APSN). These lesions are at high risk of recurrence after kidney transplantation. The complement pathway is thought to be active in this process. We used eculizumab to treat three consecutive kidney transplant recipients with posttransplant TMA due to APSN recurrence that was resistant to plasmapheresis and explored the complement deposition and apoptotic and vascular cell markers on the sequential transplant biopsies. Treatment with eculizumab resulted in a rapid and dramatic improvement of the graft function in all three patients and in improvement of the TMA lesions within the graft. None of these patients had TMA flares after eculizumab was withdrawn. At the time of TMA diagnosis, immunofluorescence studies revealed intense C5b-9 and C4d depositions at the endothelial cell surface of the injured vessels. Moreover, C5b-9 colocalized with vessels exhibiting a high rate of apoptotic cells. Examination of sequential biopsies during eculizumab therapy showed that TMA lesions, C4d and apoptotic markers were rapidly cleared but the C5b-9 deposits persisted for several months as a footprint of the TMA. Finally, we noticed that complement inhibition did not prevent the development of the chronic vascular changes associated with APSN. Eculizumab seems to be an efficient method for treating severe forms of posttransplant TMA due to APSN recurrence. Terminal complement inhibition does not prevent the development of chronic APSN. PMID:23763583

  9. Residential exposure to electric power transmission lines and risk of lymphoproliferative and myeloproliferative disorders: a case?control study

    Microsoft Academic Search

    R. M. Lowenthal; D. M. Tuck; I. C. Bray

    2007-01-01

    Background: Studies have shown an association between electromagnetic fieldsandchildhoodleukaemia.Theaimofthisstudywastodeterminewhether there is an increased risk of lymphoproliferative disorders (LPD) or myelopro- liferative disorders (MPD) associated with residence 300 m from high-voltage power lines. Methods: Case-control study of 854 patients diagnosed with LPD or MPD (including leukaemia, lymphoma and related conditions) aged 0-94 years comprising all cases diagnosed in Tasmania between 1972

  10. Notch-Deficient Skin Induces a Lethal Systemic B-Lymphoproliferative Disorder by Secreting TSLP, a Sentinel for Epidermal Integrity

    Microsoft Academic Search

    Shadmehr Demehri; Zhenyi Liu; Jonghyeob Lee; Meei-Hua Lin; Seth D Crosby; Christopher J Roberts; Perry W Grigsby; Jeffrey H Miner; Andrew G Farr; Raphael Kopan

    2008-01-01

    Epidermal keratinocytes form a highly organized stratified epithelium and sustain a competent barrier function together with dermal and hematopoietic cells. The Notch signaling pathway is a critical regulator of epidermal integrity. Here, we show that keratinocyte-specific deletion of total Notch signaling triggered a severe systemic B-lymphoproliferative disorder, causing death. RBP-j is the DNA binding partner of Notch, but both RBP-j–dependent

  11. Increased Protection from Vaccinia Virus Infection in Mice Genetically Prone to Lymphoproliferative Disorders

    PubMed Central

    Seedhom, Mina O.; Mathurin, Keisha S.; Kim, Sung-Kwon

    2012-01-01

    Mutations in the genes that encode Fas or Fas ligand (FasL) can result in poor restraints on lymphocyte activation and in increased susceptibility to autoimmune disorders. Because these mutations portend a continuously activated immune state, we hypothesized that they might in some cases confer resistance to infection. To examine this possibility, the immune response to, morbidity caused by, and clearance of vaccinia virus (VACV) Western Reserve was examined in 5- to 7-week-old Fas mutant (lpr) mice, before an overt lymphoproliferative disorder was observable. On day 6 after VACV infection, C57BL/6-lpr (B6-lpr) mice had decreased morbidity, decreased viral titers, and an increased percentage and number of CD4+ and CD8+ T cells. As early as day 2 after infection, B6-lpr mice had decreased liver and spleen viral titers and increased numbers of and increased gamma interferon (IFN-?) production by several different effector cell populations. Depletion of individual effector cell subsets did not inhibit the resistance of B6-lpr mice. Uninfected B6-lpr mice also had increased numbers of NK cells, ??+ T cells, and CD44+ CD4+ and CD44+ CD8+ T cells compared to uninfected B6 mice. Antibody to IFN-? resulted in increased virus load in both B6 and B6-lpr mice and eliminated the differences in viral titers between them. These results suggest that IFN-? produced by multiple activated leukocyte populations in Fas-deficient hosts enhances resistance to some viral infections. PMID:22438562

  12. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations

    PubMed Central

    Price, Susan; Shaw, Pamela A.; Seitz, Amy; Joshi, Gyan; Davis, Joie; Niemela, Julie E.; Perkins, Katie; Hornung, Ronald L.; Folio, Les; Rosenberg, Philip S.; Puck, Jennifer M.; Hsu, Amy P.; Lo, Bernice; Pittaluga, Stefania; Jaffe, Elaine S.; Fleisher, Thomas A.; Lenardo, Michael J.

    2014-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadenopathy and splenomegaly associated with a characteristic expansion of mature CD4 and CD8 negative or double negative T-cell receptor ??+ T lymphocytes. Patients often present with chronic multilineage cytopenias due to autoimmune peripheral destruction and/or splenic sequestration of blood cells and have an increased risk of B-cell lymphoma. Deleterious heterozygous mutations in the FAS gene are the most common cause of this condition, which is termed ALPS-FAS. We report the natural history and pathophysiology of 150 ALPS-FAS patients and 63 healthy mutation-positive relatives evaluated in our institution over the last 2 decades. Our principal findings are that FAS mutations have a clinical penetrance of <60%, elevated serum vitamin B12 is a reliable and accurate biomarker of ALPS-FAS, and the major causes of morbidity and mortality in these patients are the overwhelming postsplenectomy sepsis and development of lymphoma. With longer follow-up, we observed a significantly greater relative risk of lymphoma than previously reported. Avoiding splenectomy while controlling hypersplenism by using corticosteroid-sparing treatments improves the outcome in ALPS-FAS patients. This trial was registered at www.clinicaltrials.gov as #NCT00001350. PMID:24398331

  13. A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders.

    PubMed

    Velusamy, Thirunavukkarasu; Kiel, Mark J; Sahasrabuddhe, Anagh A; Rolland, Delphine; Dixon, Catherine A; Bailey, Nathanael G; Betz, Bryan L; Brown, Noah A; Hristov, Alexandra C; Wilcox, Ryan A; Miranda, Roberto N; Medeiros, L Jeffrey; Jeon, Yoon K; Inamdar, Kedar V; Lim, Megan S; Elenitoba-Johnson, Kojo S J

    2014-12-11

    The spectrum of cutaneous CD30-positive lymphoproliferative disorders (LPDs) includes lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. Chromosomal translocations targeting tyrosine kinases in CD30-positive LPDs have not been described. Using whole-transcriptome sequencing, we identified a chimeric fusion involving NPM1 (5q35) and TYK2 (19p13) that encodes an NPM1-TYK2 protein containing the oligomerization domain of NPM1 and an intact catalytic domain in TYK2. Fluorescence in situ hybridization revealed NPM1-TYK2 fusions in 2 of 47 (4%) primary cases of CD30-positive LPDs and was absent in other mature T-cell neoplasms (n = 151). Functionally, NPM1-TYK2 induced constitutive TYK2, signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5 activation. Conversely, a kinase-defective NPM1-TYK2 mutant abrogated STAT1/3/5 signaling. Finally, short hairpin RNA-mediated silencing of TYK2 abrogated lymphoma cell growth. This is the first report of recurrent translocations involving TYK2, and it highlights the novel therapeutic opportunities in the treatment of CD30-positive LPDs with TYK2 translocations. PMID:25349176

  14. Co-inherited mutations of Fas and caspase-10 in development of the autoimmune lymphoproliferative syndrome

    PubMed Central

    Cerutti, Elisa; Campagnoli, Maria F; Ferretti, Massimo; Garelli, Emanuela; Crescenzio, Nicoletta; Rosolen, Angelo; Chiocchetti, Annalisa; Lenardo, Michael J; Ramenghi, Ugo; Dianzani, Umberto

    2007-01-01

    Background Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder characterized by defective function of Fas, autoimmune manifestations that predominantly involve blood cells, polyclonal accumulation of lymphocytes in the spleen and lymph nodes with lymphoadenomegaly and/or splenomegaly, and expansion of TCR??+ CD4/CD8 double-negative (DN) T cells in the peripheral blood. Most frequently, it is due to Fas gene mutations, causing ALPS type Ia (ALPS-Ia). However, other mutations, namely of the FasL gene (ALPS-Ib) and the caspase-10 gene (ALPS-II) are occasionally detected, whereas some patients do not present any known mutations (ALPS-III). Recently, mutations of the NRAS gene have been suggested to cause ALPS-IV. Results This work reports two patients that are combined heterozygous for single nucleotide substitutions in the Fas and caspase-10 genes. The first patient carried a splice site defect suppressing allele expression in the Fas gene and the P501L substitution in caspase-10. The second had a mutation causing a premature stop codon (Q47X) in the Fas gene and the Y446C substitution in caspase-10. Fas expression was reduced and caspase-10 activity was decreased in both patients. In both patients, the mutations were inherited from distinct healthy parents. Conclusion These data strongly suggest that co-transmission of these mutation was responsible for ALPS. PMID:17999750

  15. Peripheral T-cell and NK cell lymphoproliferative disorders: cell of origin, clinical and pathological implications.

    PubMed

    Inghirami, Giorgio; Chan, Wing C; Pileri, Stefano

    2015-01-01

    T-cell lymphoproliferative disorders are a heterogeneous group of neoplasms with distinct clinical-biological properties. The normal cellular counterpart of these processes has been postulated based on functional and immunophenotypic analyses. However, T lymphocytes have been proven to be remarkably capable of modulating their properties, adapting their function in relationship with multiple stimuli and to the microenvironment. This impressive plasticity is determined by the equilibrium among a pool of transcription factors and by DNA chromatin regulators. It is now proven that the acquisition of specific genomic defects leads to the enforcement/activation of distinct pathways, which ultimately alter the preferential activation of defined regulators, forcing the neoplastic cells to acquire features and phenotypes distant from their original fate. Thus, dissecting the landscape of the genetic defects and their functional consequences in T-cell neoplasms is critical not only to pinpoint the origin of these tumors but also to define innovative mechanisms to re-adjust an unbalanced state to which the tumor cells have become addicted and make them vulnerable to therapies and targetable by the immune system. In our review, we briefly describe the pathological and clinical aspects of the T-cell lymphoma subtypes as well as NK-cell lymphomas and then focus on the current understanding of their pathogenesis and the implications on diagnosis and treatment. PMID:25510275

  16. Malignant lymphoma-associated autoimmune diseases - a descriptive epidemiological study

    Microsoft Academic Search

    László Váróczy; Lajos Gergely; Margit Zeher; Gyula Szegedi; ÁrpÁd Illés

    2002-01-01

    Lymphoproliferative disorders and autoimmune diseases have some common aspects in their clinical appearance. We reviewed 940 patient charts with malignant lymphomas to assess the rate of associated autoimmune diseases. Of 421 non-Hodgkin's lymphoma (NHL) patients (230 males, 191 females), 32 (7.6%) had an autoimmune disease (26 females, six males, mean age 48.3 years). The most common diagnosis was Sjögren's syndrome.

  17. Vaccine by chicken line interaction alters the protective efficacy against challenge with a very virulent plus strain of Marek's disease virus in white leghorn chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by Marek’s disease virus (MDV), an oncogenic and highly contagious a-herpesvirus. MD has been controlled by vaccination but sporadic outbreaks of MD still occur in some parts of the world. Efforts to improve vaccine ef...

  18. Usefulness of IGH/TCR PCR studies in lymphoproliferative disorders with inconclusive clonality by flow cytometry.

    PubMed

    Ribera, Jordi; Zamora, Lurdes; Juncŕ, Jordi; Rodríguez, Inés; Marcé, Silvia; Cabezón, Marta; Millá, Fuensanta

    2014-01-01

    In up to 5-15% of studies of lymphoproliferative disorders (LPD), flow cytometry (FCM) or immunomorphologic methods cannot discriminate malignant from reactive processes. The aim of this work was to determine the usefulness of PCR for solving these diagnostic uncertainties. We analyzed IGH and TCR? genes by PCR in 106 samples with inconclusive FCM results. A clonal result was registered in 36/106 studies, with a LPD being confirmed in 27 (75%) of these cases. Specifically, 9/9 IGH clonal and 16/25 TCR? clonal results were finally diagnosed with LPD. Additionally, two clonal TCR? samples with suspicion of undefined LPD were finally diagnosed with T LPD. Although polyclonal results were obtained in 47 of the cases studied (38 IGH and nine TCR?), hematologic neoplasms were diagnosed in 4/38 IGH polyclonal and in 1/9 TCR? polyclonal studies. There were also 14 PCR polyclonal results (four IGH, 10 TCR?), albeit nonconclusive. Of these, 2/4 were eventually diagnosed with B-cell lymphoma and 3/10 with T-cell LPD. In eight IGH samples, the results of PCR techniques were noninformative but in 3/8 cases a B lymphoma was finally confirmed. We concluded that PCR is a useful technique to identify LPD when FCM is inconclusive. A PCR clonal B result is indicative of malignancy but IGH polyclonal and nonconclusive results do not exclude lymphoid neoplasms. Interpretation of T-cell clonality should be based on all the available clinical and analytical data. PMID:23943305

  19. Usefullness of IGH/TCR PCR studies in lymphoproliferative disorders with inconclusive clonality by flow cytometry.

    PubMed

    Ribera, Jordi; Zamora, Lurdes; Juncŕ, Jordi; Rodríguez, Inés; Marcé, Silvia; Cabezón, Marta; Millá, Fuensanta

    2013-07-25

    In up to 5-15% of studies of lymphoproliferative disorders (LPD) flow cytometry (FCM) or immunomorphologic methods cannot discriminate malignant from reactive processes. The aim of this work was to determine the usefulness of PCR for solving these diagnostic uncertainties. We analyzed IGH and TCR? genes by PCR in 106 samples with inconclusive FCM results. A clonal result was registered in 36/106 studies, with a LPD being confirmed in 27 (75%) of these cases. Specifically, 9/9 IGH clonal and 16/25 TCR? clonal results were finally diagnosed with LPD. Additionally, 2 clonal TCR? samples with suspicion of undefined LPD were finally diagnosed with T LPD. Although polyclonal results were obtained in 47 of the cases studied (38 IGH and 9 TCR?), hematologic neoplasms were diagnosed in 4/38 IGH polyclonal and in 1/9 TCR? polyclonal studies. There were also 14 PCR polyclonal results (4 IGH, 10 TCR?), albeit non-conclusive. Of these, 2/4 were eventually diagnosed with B-cell lymphoma and 3/10 with T-cell LPD. In 8 IGH samples the results of PCR techniques were non-informative but in 3/8 cases a B lymphoma was finally confirmed. We concluded that PCR is a useful technique to identify LPD when FCM is inconclusive. A PCR clonal B result is indicative of malignancy but IGH polyclonal and non-conclusive results do not exclude lymphoid neoplasms. Interpretation of T-cell clonality should be based on all the available clinical and analytical data. © 2013 Clinical Cytometry Society. PMID:23894019

  20. Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients

    PubMed Central

    Compagno, Nicolň; Cinetto, Francesco; Semenzato, Gianpietro; Agostini, Carlo

    2014-01-01

    Intravenous immunoglobulin replacement therapy represents the standard treatment for hypogammaglobulinemia secondary to B-cell lymphoproliferative disorders. Subcutaneous immunoglobulin infusion is an effective, safe and well-tolerated treatment approach in primary immunodeficiencies but no extensive data are available on their use in secondary hypogammaglobulinemia, a frequent phenomenon occurring after treatment with anti-CD20 monoclonal antibodies in lymphoproliferative disorders. In this retrospective study we evaluated efficacy (serum IgG trough levels, incidence of infections per year, need for antibiotics) and safety (number of adverse events) of intravenous (300 mg/kg/4 weeks) versus subcutaneous (75 mg/kg/week) immunoglobulin replacement therapy in 61 patients. In addition, the impact of the infusion methods on quality of life was compared. All patients were treated with subcutaneous immunoglobulin, and 33 out of them had been previously treated with intravenous immunoglobulin. Both treatments appeared to be effective in replacing Ig production deficiency and in reducing the incidence of infectious events and the need for antibiotics. Subcutaneous immunoglobulin obtained a superior benefit when compared to intravenous immunoglobulin achieving higher IgG trough levels, lower incidence of overall infection and need for antibiotics. The incidence of serious bacterial infections was similar with both infusion ways. As expected, a lower number of adverse events was registered with subcutaneous immunoglobulin, compared to intravenous immunoglobulin, with no serious adverse events. Finally, we observed an improvement in health-related quality of life parameters after the switch to subcutaneous immunoglobulin. Our results suggest that subcutaneous immunoglobulin is safe and effective in patients with hypogammaglobulinemia associated to lymphoproliferative disorders. PMID:24682509

  1. [Kidney allograft: a target for systemic disease].

    PubMed

    Canaud, Guillaume; Legendre, Christophe

    2012-03-01

    Recurrence of disease after transplantation is frequent and represents the third cause of allograft loss. Recurrence of lupus nephritis after transplantation is rare. Kidney transplantation in patients with antiphospholipid syndrome or lupus anticoagulant is challenging due to the high risk of immediate post-transplant thrombosis and bleeding risk associated to the subsequent anticoagulation. Moreover, vascular changes associated to the presence of antiphospholipid antibodies negatively impact allograft rate survival. Recurrence of pauci immune glomerulonephritis or Goodpasture syndrome is exceptional. PMID:22244721

  2. A comparative evaluation of the protective efficacy of rMd5-delta-Meq and CV1988/Rispens against a vv+ strain of Marek's disease virus infection in a series of recombinant congenic strains of white leghorn chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by a highly infectious, oncogenic alpha-herpesvirus known as Marek’s disease virus (MDV). MD is presently controlled by vaccination. Current MD vaccines include attenuated serotype 1 strains (e.g. CVI988/Rispens), avir...

  3. Evolution of Marek’s disease – A paradigm for incessant race between the pathogen and the host

    Microsoft Academic Search

    Venugopal Nair

    2005-01-01

    Marek’s disease (MD) is a highly contagious lymphoproliferative disease of poultry caused by the oncogenic herpesvirus designated Marek’s disease virus (MDV). MD has a worldwide distribution and is thought to cause an annual loss over US$1 bn to the poultry industry. Originally described as a paralytic disease, today MD is mostly manifested as an acute disease with tumours in multiple

  4. Castleman’s Disease, a Case report

    PubMed Central

    Reddy, Ranga; Singhania, Ankit; George, Ajay; Kumar, Ranjan; Kumar, Sanjay

    2011-01-01

    Introduction: Castleman's disease is a rare lymphoproliferative disorder which may be confused with other causes of lymphadenopathy. Case Report: Here we report a case of unicentric Castleman's disease presenting with cervical lymphadenopathy. The patient was treated with complete surgical excision of lesion and was disease free at the time of reporting this article. This case has been reported for its rarity. Conclusion: Though castleman’s disease is a relatively rare entity it should be strongly considered in the differential diagnosis of cervical lymphadenopathy. PMID:24303376

  5. Role of Hypertension and Anaemia in Left Ventricular Remodelling in Patient with Renal Allograft in the First Post-transplant Year

    PubMed Central

    Jasminka, Dzemidzic; Rasic, Senija; Rebic, Damir; Uncanin, Snezana

    2015-01-01

    Background: Hypertension (HT) and renal anaemia (RA) are well-established markers of cardiovascular risk in patients with chronic kidney disease (CKD). They appear to be the stimuli for left ventricular hypertrophy (LVH), who significantly participates in cardiac complications in uremic patients. Hypertension is extremely common after kidney transplantation (KTx) and it has been observed in up to 75% of patients. The prevalence of post-renal transplant anaemia (PTA) is variable (up to 30%) and several factors such as graft function contribute towards its pathophysiology. Aim: The aim of this study was to analyze the impact of blood pressure and anaemia on LV remodelling in first year after transplantation comparing echocardiographic findings before and twelve months after transplantation had done. Methods: In five years retrospective-prospective study we followed up 30 patients with renal allograft in first post-transplant year. During the study values of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), blood hemoglobin (Hgb), serum creatinine and creatinine clearance were monitored monthly. Results: Before transplantation (Tx) 86% of patients had HT, and RA was confirmed in all patients. Normal echocardiographic findings had 33% of patients and 67% of patients had echocardiographic sings of LVH. Before renal transplantation group with LVH had statistically higher the mean values of blood pressure (MBP) (p=0.053) compared to group with diastolic (LVDDF) (p=0.0047) and systolic-diastolic dysfunction (LVSDDF) (p=0.0046). The values of SBP and DBP positively correlated with LV mass index (LVMI) in the group of patients with LVH (p=0.0007 and p=0.0142). The values of Hgb was statistically higher in group with normal LV mass index compared to LVH (p=0.019), with negative correlation between LVMI and values of Hgb in the patients group with LV hypertrophy (p=0.009). After the first year of transplantation, 63% of patients showed normal LV mass index and 37% remained with echocardiographic findings of the LVH. The values of SBP and values of Hgb in both groups, as well as values of DBP in group of LVH were statistically different in compare with data before transplantation (p<0.05). The positive echocardiographic remodelling of LV significantly correlated with the increase of Hgb values (p=0.05), but without significant correlation with the decrease of the mean SBP and DBP. Conclusion: These results confirmed that positive echocardiographic remodelling of left ventricle after successful renal transplantation is complex process depended on many risk factors and elimination of uremia- related factors is a priority. PMID:26005386

  6. Construction of a YAC contig and STS map spanning 2.5 Mbp in Xq25, the critical region for the X-linked lymphoproliferative (XLP) gene

    SciTech Connect

    Lanyi, A.; Li, B.F.; Li, S. [Univ. of Nebraska Medical Center, Omaha, NE (United States)] [and others

    1994-09-01

    X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability in Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia or B-cell lymphoma. The XLP gene lies within a 10 cM region in Xq25 between DXS42 and DXS10. Initial chromosome studies revealed an interstitial, cytogenetically visible deletion in Xq25 in one XLP family (43-004). We estimated the size of the Xq25 deletion by dual laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mbp of DNA sequences. To further delineate the deletion we performed a series of pulsed field gel electrophoresis (PFGE) analyses which showed that DXS6 and DXS100, two Xq25-specific markers, are missing from 45-004 DNA. Five yeast artificial chromosomes (YACs) from a chromosome X specific YAC library containing sequences deleted in patient`s 43-004 DNA were isolated. These five YACs did not overlap, and their end fragments were used to screen the CEPH MegaYAC library. Seven YACs were isolated from the CEPH MegaYAC library. They could be arranged into a contig which spans between DXS6 and DXS100. The contig contains a minimum of 2.5 Mbp of human DNA. A total of 12 YAC end clone, lambda subclones and STS probes have been used to order clones within the contig. These reagents were also used in Southern blot and patients showed interstitial deletions in Xq25. The size of these deletions range between 0.5 and 2.5 Mbp. The shortest deletion probably represents the critical region for the XLP gene.

  7. TP53 Gene Mutation, an Unfavorable Prognostic Factor for Malignant Lymphomas in Autoimmune Diseases

    Microsoft Academic Search

    Yoshihiko Hoshida; Tadashi Hongyo; Jing-Xian Xu; Toru Sasaki; Yasuhiko Tomita; Taisei Nomura; Katsuyuki Aozasa

    2005-01-01

    Objectives: To investigate whether mutations of the TP53 tumor suppressor gene are associated with a poor prognosis in lymphoproliferative disorders (LPD) developing in patients with a history of autoimmune disease (AID). Methods: Fifty patients, 15 males and 35 females ranging in age from 23 to 83 (median, 61) years, were examined. Rheumatoid arthritis (21 cases) is the commonest type of

  8. CMV reactivation drives posttransplant T-cell reconstitution and results in defects in the underlying TCR? repertoire.

    PubMed

    Suessmuth, Yvonne; Mukherjee, Rithun; Watkins, Benjamin; Koura, Divya T; Finstermeier, Knut; Desmarais, Cindy; Stempora, Linda; Horan, John T; Langston, Amelia; Qayed, Muna; Khoury, Hanna J; Grizzle, Audrey; Cheeseman, Jennifer A; Conger, Jason A; Robertson, Jennifer; Garrett, Aneesah; Kirk, Allan D; Waller, Edmund K; Blazar, Bruce R; Mehta, Aneesh K; Robins, Harlan S; Kean, Leslie S

    2015-06-18

    Although cytomegalovirus (CMV) reactivation has long been implicated in posttransplant immune dysfunction, the molecular mechanisms that drive this phenomenon remain undetermined. To address this, we combined multiparameter flow cytometric analysis and T-cell subpopulation sorting with high-throughput sequencing of the T-cell repertoire, to produce a thorough evaluation of the impact of CMV reactivation on T-cell reconstitution after unrelated-donor hematopoietic stem cell transplant. We observed that CMV reactivation drove a >50-fold specific expansion of Granzyme B(high)/CD28(low)/CD57(high)/CD8(+) effector memory T cells (Tem) and resulted in a linked contraction of all naive T cells, including CD31(+)/CD4(+) putative thymic emigrants. T-cell receptor ? (TCR?) deep sequencing revealed a striking contraction of CD8(+) Tem diversity due to CMV-specific clonal expansions in reactivating patients. In addition to querying the topography of the expanding CMV-specific T-cell clones, deep sequencing allowed us, for the first time, to exhaustively evaluate the underlying TCR repertoire. Our results reveal new evidence for significant defects in the underlying CD8 Tem TCR repertoire in patients who reactivate CMV, providing the first molecular evidence that, in addition to driving expansion of virus-specific cells, CMV reactivation has a detrimental impact on the integrity and heterogeneity of the rest of the T-cell repertoire. This trial was registered at www.clinicaltrials.gov as #NCT01012492. PMID:25852054

  9. CMV reactivation drives posttransplant T-cell reconstitution and results in defects in the underlying TCR? repertoire

    PubMed Central

    Suessmuth, Yvonne; Mukherjee, Rithun; Watkins, Benjamin; Koura, Divya T.; Finstermeier, Knut; Desmarais, Cindy; Stempora, Linda; Horan, John T.; Langston, Amelia; Qayed, Muna; Khoury, Hanna J.; Grizzle, Audrey; Cheeseman, Jennifer A.; Conger, Jason A.; Robertson, Jennifer; Garrett, Aneesah; Kirk, Allan D.; Waller, Edmund K.; Blazar, Bruce R.; Mehta, Aneesh K.; Robins, Harlan S.

    2015-01-01

    Although cytomegalovirus (CMV) reactivation has long been implicated in posttransplant immune dysfunction, the molecular mechanisms that drive this phenomenon remain undetermined. To address this, we combined multiparameter flow cytometric analysis and T-cell subpopulation sorting with high-throughput sequencing of the T-cell repertoire, to produce a thorough evaluation of the impact of CMV reactivation on T-cell reconstitution after unrelated-donor hematopoietic stem cell transplant. We observed that CMV reactivation drove a >50-fold specific expansion of Granzyme Bhigh/CD28low/CD57high/CD8+ effector memory T cells (Tem) and resulted in a linked contraction of all naive T cells, including CD31+/CD4+ putative thymic emigrants. T-cell receptor ? (TCR?) deep sequencing revealed a striking contraction of CD8+ Tem diversity due to CMV-specific clonal expansions in reactivating patients. In addition to querying the topography of the expanding CMV-specific T-cell clones, deep sequencing allowed us, for the first time, to exhaustively evaluate the underlying TCR repertoire. Our results reveal new evidence for significant defects in the underlying CD8 Tem TCR repertoire in patients who reactivate CMV, providing the first molecular evidence that, in addition to driving expansion of virus-specific cells, CMV reactivation has a detrimental impact on the integrity and heterogeneity of the rest of the T-cell repertoire. This trial was registered at www.clinicaltrials.gov as #NCT01012492. PMID:25852054

  10. Lymphoproliferative and gamma interferon responses to stress-regulated Mycobacterium avium subsp. paratuberculosis recombinant proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease in ruminants is a chronic infection of the intestines caused by Mycobacterium avium subsp. paratuberculosis. Economic losses associated with Johne’s disease arise due to premature culling, reduced production of milk and wool and mortalities. The disease is characterised by a long inc...

  11. Immunotherapy for EBV-associated malignancies

    Microsoft Academic Search

    Anna Merlo; Riccardo Turrini; Riccardo Dolcetti; Paola Zanovello; Antonio Rosato

    2011-01-01

    Since 1995 to date, more than 250 patients with EBV-related diseases received virus-specific CTL. Cell therapy proved to be\\u000a safe and effective, and achieved some complete remissions also in patients who failed all previous standard treatments. The\\u000a first clinical results with EBV-specific CTL were obtained for both prophylaxis and treatment of post-transplant lymphoproliferative\\u000a disease arising in stem cell transplant or

  12. Early post-transplant immune monitoring can predict long-term kidney graft survival: soluble CD30 levels, anti-HLA antibodies and IgA-anti-Fab autoantibodies.

    PubMed

    Amirzargar, Mohammad Ali; Amirzargar, Aliakbar; Basiri, Abbas; Hajilooi, Mehrdad; Roshanaei, Ghodratollah; Rajabi, Gholamreza; Mohammadiazar, Sina; Solgi, Ghasem

    2014-01-01

    This study aimed to investigate the predictive power of anti-HLA antibodies, sCD30 levels and IgA-anti-Fab autoantibody before and early after transplantation in relation to long-term kidney allograft survival. Pre- and post-transplant sera samples of 59 living-unrelated donor kidney recipients were tested for above risk factors by enzyme-linked immunoabsorbent assay. 15 out of 59 cases experienced rejection episodes (failure group). Pre- and post-transplant high sCD30 levels were significantly associated with graft failure (P=0.02 and P=0.004) and decreased 4 year graft survival (P = 0.009 and P = 0.001). Higher frequency of post-transplant HLA class-II antibody in the absence of class-I antibody was observed in failure group (P=0.007). Patients with post-transplant HLA class-I and class-II antibodies either alone or in combination showed significant lower 4 year graft survival. Recipients with high sCD30 levels in the presence of HLA class-I or class-II antibodies within 2 weeks post-transplant had poor graft survival (P = 0.004 and P = 0.002, respectively). High levels of post-transplant IgA-anti-Fab antibody was more frequent in functioning-graft patients (P = 0.00001), correlated with decreased serum creatinine levels (P = 0.01) and associated with improved graft survival (P = 0.008). Our findings indicate the deleterious effect of early post-transplant HLA antibodies and increased sCD30 levels dependently and protective effect of IgA-anti-Fab antibodies on long-term renal graft outcomes. PMID:24055694

  13. Routine use of bendamustine and rituximab combination therapy in consecutive patients with lymphoproliferative diseases: A survey from Tyrolean hospitals

    Microsoft Academic Search

    Christian Waldthaler; Reinhard Stauder; Michael Schnallinger; Stephan Schreieck; Judith Hager; Horst Oexle; Günther Zangerl; Irmgard Verdorfer; Günther Gastl; Michael Fiegl

    2011-01-01

    \\u000a Zusammenfassung  HINTERGRUND: Ziel war es, den therapeutischen Nutzen und das Nebenwirkungsprofil von Bendamustin\\/Rituximab im klinischen Alltag\\u000a im Spektrum der unterschiedlichen Non-Hodgkin Lymphome zu analysieren. PATIENTEN UND METHODEN: Therapieergebnisse und Nebenwirkungsprofil\\u000a bei 71 Patienten aus 5 verschiedenen Zentren wurden retrospektiv erhoben, wobei in konsekutiver Weise alle Patienten, welche\\u000a eine Chemoimmuntherapie mit Bendamustin und Rituximab erhielten, dokumentiert wurden. ERGEBNISSE: Als wesentliche Therapie-assoziierte\\u000a Toxizität

  14. Experimental models of lymphoproliferative disease. The mouse as a model for human non-Hodgkin's lymphomas and related leukemias.

    PubMed Central

    Pattengale, P. K.; Taylor, C. R.

    1983-01-01

    The present review focuses on the mouse as an experimental immunopathologic model for human non-Hodgkin's lymphomas and related leukemias. Immunomorphologic evidence is presented that clearly demonstrates that B- and T-cell subtypes of mouse (murine) lymphoma/leukemia closely resemble and are analogous to B- and T-cell subtypes of human lymphoma/leukemia as defined by recently proposed immunomorphologic classifications. Further evidence is presented that favors the hypothesis that certain types of murine and human B-cell lymphoma develop out of prodromal, prelymphomatous states, which exhibit antecedent morphologic and immunologic abnormalities. The many experimental advantages of the murine systems are stressed, as well as the concept that the presently defined immunomorphologic approach should be effectively combined with molecular and cytogenetic parameters. Images Table 6 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 10 Table 9 Figure 11 Figure 12 Figure 13 PMID:6605691

  15. [Rosai-Dorfman disease: therapeutic issues in 2 cases].

    PubMed

    Ben Turkia, H; Ben Romdhane, M; Azzouz, H; Ben Chehida, A; Slim Abdelmoula, M; Benabdelaziz, R; Tebib, N; Ben Messaoud, M; Sahtout, S; Chelly, I; Zitouna, M; Mnif, E; Ben Dridi, M F

    2011-11-01

    Rosai-Dorfman disease (RDD) is a benign lymphoproliferative disorder characterized by cervical lymph node enlargement with a consistent risk of airway compression and esthetic damage. Extranodal localizations are also described. There is no therapeutic consensus for pediatric forms of RDD. Through 2 pediatric cases with nodal involvement in 1 patient and a sinonasal and soft tissue localization in the other, we focus on the management problems of both nodal and extranodal RDD. PMID:21992893

  16. A Phase I Trial of Epstein-Barr Virus Gp350 Vaccine for Children With Chronic Kidney Disease Awaiting Transplantation

    Microsoft Academic Search

    Lesley Rees; E Jane Tizard; Andrew J. Morgan; W David Cubitt; Susan Finerty; Titilade A. Oyewole-Eletu; Karen Owen; Collin Royed; Servi J. Stevens; Rukshana C. Shroff; Manjit K. Tanday; A Douglas Wilson; Jaap M. Middeldorp; Peter L. Amlot; Neil M. Steven

    2009-01-01

    Background. Vaccination against Epstein-Barr virus (EBV), inducing an antibody response to the envelope glycoprotein gp350, might protect EBV-negative children with chronic kidney disease from lymphoproliferative disease after transplantation. Methods. A phase I trial recruited children with chronic kidney disease to two successive cohorts given three injections of 12.5 mu g (n=6) and 25 mu g (n=10) recombinant gp350\\/alhydrogel vaccine over

  17. Molecular Cytogenetic Delineation of a Novel Critical Genomic Region in Chromosome Bands 11q22.3-923.1 in Lymphoproliferative Disorders

    Microsoft Academic Search

    Stephan Stilgenbauer; Peter Liebisch; Michael R. James; Martin Schroder; Brigitte Schlegelberger; Konstanze Fischer; Martin Bentz; Peter Lichter; Hartmut Dohner

    1996-01-01

    Aberrations of the long arm of chromosome 11 are among the most common chromosome abnormalities in lymphoproliferative disorders (LPD). Translocations involving BCL1 at 11q13 are strongly associated with mantle cell lymphoma. Other nonrandom aberrations, especially deletions and, less frequently, translocations, involving bands 11q21-923 have been identified by chromosome banding analysis. To date, the critical genomic segment and candidate genes involved

  18. Increased incidence of EBV-associated lymphoproliferative disorders after allogeneic stem cell transplantation from matched unrelated donors due to a change of T cell depletion technique

    Microsoft Academic Search

    E Meijer; ICM Slaper-Cortenbach; SFT Thijsen; AW Dekker; LF Verdonck

    2002-01-01

    Here, the influence of T vs T and B cell depletion on the incidence of EBV-associated lymphoproliferative disorder (EBV-LPD) after bone marrow transplantation (BMT) from a matched unrelated donor (MUD) is analyzed. From 1982 to 1997 the soy bean agglutinin\\/sheep red blood cell (SBA\\/SRBC) method was used for T cell depletion. This technique is well established, but the use of

  19. Management of Febrile Neutropenia – a German Prospective Hospital Cost Analysis in Lymphoproliferative Disorders, Non-Small Cell Lung Cancer, and Primary Breast Cancer

    Microsoft Academic Search

    Angela Ihbe-Heffinger; Bernadette J. Paessens; Christoph von Schilling; Margarita Shlaen; Nina Gottschalk; Karin Berger; Rudolf Bernard; Marion Kiechle; Christian Peschel; Volker R. Jacobs

    2011-01-01

    SummaryBackground: Febrile neutropenia\\/leukopenia (FN\\/FL) is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy, but German data on economic consequences are limited. Patients and Methods: A prospective, multicentre, longitudinal, observational study was carried out to evaluate the occurrence of FN\\/FL and its impact on health resource utilization and costs in non-small cell lung cancer (NSCLC), lymphoproliferative disorder (LPD), and primary breast

  20. Comparative Analysis of Human Cytomegalovirus-Specific CD4+ T-Cell Frequency and Lymphoproliferative Response in Human Immunodeficiency Virus-Positive Patients

    Microsoft Academic Search

    GIAMPIERO PICCININI; GIUDITTA COMOLLI; EMILIA GENINI; DANIELE LILLERI; ROBERTO GULMINETTI; RITA MACCARIO; MARIA GRAZIA REVELLO; GIUSEPPE GERNA

    2001-01-01

    Evaluation of human cytomegalovirus (HCMV)-specific T-helper immunity could contribute in optimizing anti-HCMV therapy in human immunodeficiency virus (HIV)-infected patients. Testin the lymphoproliferative response (LPR) is the standard technique used to evaluate T-helper response, but its use in the routine diagnostic laboratory setting can be problematic. The most promising new alternative technique is the determination of HCMV-specific CD4 T-cell frequency by

  1. Salvage of compromised renal vessels in kidney transplantation using third-party cadaveric extenders: impact on posttransplant anti-HLA antibody formation.

    PubMed

    Goel, Mahesh C; Flechner, Stuart M; El-Jack, Mohammed; Veniro, John; Kingman, Lynne; Modlin, Charles; Cook, Daniel J

    2004-06-27

    Kidney transplant surgery can be complicated by short, attenuated, or injured renal vessels which are now more frequently encountered with laparoscopic right donor nephrectomy. We describe a technique to overcome this problem in seven recipients (2 cadaveric and 5 living donors) by constructing third-party "vascular extenders" using cadaveric iliac vessels retrieved previously and preserved at 4 degrees C in University of Wisconsin solution. Mean vessel cold storage time was 25.7 days (range, 2-56 days). Immunosuppression consisted of sirolimus, mycophenolate mofetil, and steroids. Prompt reperfusion of all allografts was observed, and there were no surgical complications. Integrity of the extenders was confirmed using serial MAG3 renal scans and magnetic resonance angiography. Mean serum creatinine was 1.44 mg/dl at 19.2 months (range, 0.7-2 mg/dl at 3-31 months). Each recipient had a negative posttransplant kidney donor specific flow cytometry crossmatch. Two recipients developed HLA antibodies, one to DR7 and another DR13 (mismatched to the vessel donor) at 4 and 11 months posttransplant, respectively. PMID:15223911

  2. The role of molecular analysis of immunoglobulin and T cell receptor gene rearrangements in the diagnosis of lymphoproliferative disorders

    PubMed Central

    Langerak, A; van Krieken, J H J M; Wolvers-Tettero, I; Kerkhof, E; Mulder, A; Vrints, L; Coebergh, J; Schuuring, E; Kluin, P.; van Dongen, J J M

    2001-01-01

    Aims—To investigate whether the analysis of immunoglobulin (Ig)/T cell receptor (TCR) rearrangements is useful in the diagnosis of lymphoproliferative disorders. Methods—In a series of 107 consecutive cases with initial suspicion of non-Hodgkin's lymphoma (NHL), Southern blot (SB) analysis of Ig/TCR rearrangements was performed. Results—In 98 of 100 histopathologically conclusive cases, Ig/TCR gene results were concordant. In one presumed diffuse large B cell lymphoma (DLCL) and one follicular lymphoma (FL) case no clonality could be detected by SB analysis, or by polymerase chain reaction (PCR) at second stage. In the DLCL, sampling error might have occurred; the FL was revised after an initial diagnosis of reactivity. In many of the histopathologically inconclusive cases Ig/TCR gene SB analysis was helpful, giving support for the histopathological suspicion. However, because of a lack of (clinical) follow up data this could not be confirmed in a few cases. Conclusions—Experienced haematopathologists or a pathologist panel can diagnose malignant versus reactive lesions in most cases without the need for Ig/TCR gene analysis and can select the 5–10% of cases that might benefit from molecular clonality studies. Key Words: B cell lymphoma • immunoglobulin and T cell receptor genes • clonality analysis • Southern blotting PMID:11429433

  3. B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders

    PubMed Central

    Wilcox, Ryan A.; Feldman, Andrew L.; Wada, David A.; Yang, Zhi-Zhang; Comfere, Nneka I.; Dong, Haidong; Kwon, Eugene D.; Novak, Anne J.; Markovic, Svetomir N.; Pittelkow, Mark R.; Witzig, Thomas E.

    2009-01-01

    Stromal elements present within the tumor microenvironment may suppress host immunity and promote the growth of malignant lymphocytes in B cell–derived non-Hodgkin lymphoma (NHL). In contrast, little is known about the microenvironment's role in T cell–derived NHL. B7-H1 (PD-L1, CD274), a member of the B7 family of costimulatory/coinhibitory ligands expressed by both malignant cells and stromal cells within the tumor microenvironment, has emerged as an important immune modulator capable of suppressing host immunity. Therefore, B7-H1 expression and function were analyzed in cutaneous and peripheral T-cell NHL. B7-H1 was expressed by tumor cells, monocytes, and monocyte-derived cells within the tumor microenvironment in T-cell NHL and was found to inhibit T-cell proliferation and promote the induction of FoxP3+ regulatory T cells. Collectively, the data presented provide the first evidence implicating B7-H1 in the suppression of host immunity in T-cell lymphoproliferative disorders and suggest that the targeting of B7-H1 may represent a novel therapeutic approach. PMID:19597183

  4. Liver transplantation for nonalcoholic fatty liver disease: new challenges and new opportunities.

    PubMed

    Shaker, Mina; Tabbaa, Adam; Albeldawi, Mazen; Alkhouri, Naim

    2014-05-14

    Nonalcoholic fatty liver disease (NAFLD) is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world. Development of graft steatosis is a significant problem during the post-transplant course, which may happen as a recurrence of pre-existing disease or de novo NAFLD. There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome, immune-suppressive medications, genetics and others. There are few studies that assessed the effects of NAFLD on graft and patient survival; most of them were limited by the duration of follow up or by the number of patients. With this review article we will try to shed light on post-liver transplantation NAFLD, significance of the disease, how it develops, risk factors, clinical course and treatment options. PMID:24833862

  5. Liver transplantation for nonalcoholic fatty liver disease: New challenges and new opportunities

    PubMed Central

    Shaker, Mina; Tabbaa, Adam; Albeldawi, Mazen; Alkhouri, Naim

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world. Development of graft steatosis is a significant problem during the post-transplant course, which may happen as a recurrence of pre-existing disease or de novo NAFLD. There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome, immune-suppressive medications, genetics and others. There are few studies that assessed the effects of NAFLD on graft and patient survival; most of them were limited by the duration of follow up or by the number of patients. With this review article we will try to shed light on post-liver transplantation NAFLD, significance of the disease, how it develops, risk factors, clinical course and treatment options. PMID:24833862

  6. Lymphoproliferative and gamma interferon responses to stress-regulated Mycobacterium avium subsp. paratuberculosis recombinant proteins.

    PubMed

    Gurung, Ratna B; Begg, Douglas J; Purdie, Auriol C; de Silva, Kumudika; Bannantine, John P; Whittington, Richard J

    2014-06-01

    Johne's disease in ruminants is a chronic infection of the intestines caused by Mycobacterium avium subsp. paratuberculosis. An important strategy to control disease is early detection, and a potentially efficient method for early detection is measurement of cell-mediated immune responses developed by the host in response to exposure or infection. One method is to measure lymphoproliferation and cytokine release from the host cells when exposed to the organism or parts of the organism. In this study, 10 recombinant M. avium subsp. paratuberculosis proteins known to be upregulated under in vitro stress conditions were evaluated by examining their ability to evoke memory as a result of exposure by vaccination or oral challenge with live Mycobacterium avium subsp. paratuberculosis. Out of 10 proteins, MAP2698c was found to induce higher cell-mediated immune responses in vaccinated and challenged sheep in comparison to healthy controls. The findings suggest that not all stress-regulated proteins have the diagnostic potential to detect cell-mediated immune responses in ovine paratuberculosis. PMID:24695774

  7. Tumor Microenvironment and Immune Effects of Antineoplastic Therapy in Lymphoproliferative Syndromes

    PubMed Central

    Álvaro, Tomás; de la Cruz-Merino, Luis; Henao-Carrasco, Fernando; Villar Rodríguez, José Luis; Vicente Baz, David; Codes Manuel de Villena, Manuel; Provencio, Mariano

    2010-01-01

    Lymphomas represent a wide group of heterogenic diseases with different biological and clinical behavior. The underlying microenvironment-specific composition seems to play an essential role in this scenario, harboring the ability to develop successful immune responses or, on the contrary, leading to immune evasion and even promotion of tumor growth. Depending on surrounding lymphoid infiltrates, lymphomas may have different prognosis. Moreover, recent evidences have emerged that confer a significant impact of main lymphoma's treatment over microenvironment, with clinical consequences. In this review, we summarize these concepts from a pathological and clinical perspective. Also, the state of the art of lymphoma's anti-idiotype vaccine development is revised, highlighting the situations where this strategy has proven to be successful and eventual clues to obtain better results in the future. PMID:20814546

  8. [Transfer of skills: implementing post-transplant follow-up care status for transplant nurses: a report by the SFGM-TC].

    PubMed

    Cornillon, J; Peffault de Latour, R; Apaza, S; Bourg, M-A; Courbon, C; Evard, S; Guiraud, M; Le Bars, L; Petit, S; Magro, L; Schmitt, S; Tardieu, L; Samsonova, O; Tipton, R; Yakoub-Agha, I

    2014-08-01

    The number of Hematopoietic Stem Cell Transplantations has globally taken off in the past decade. However, this increase in transplantation activity has put in the spotlight the need to create a special transplantation-skilled population of nurses. This type of specialisation allocated solely to this activity has not existed within the French nursing community until now. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) sets up its forth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here we report our results and recommendations regarding the implementation of a transplant nurse status for post-transplant follow-up care. PMID:24972456

  9. Impact on health-related quality of life in kidney transplant recipients with late posttransplant anemia administered darbepoetin alfa: results from the STRATA study.

    PubMed

    Bloom, R D; Bolin, P; Gandra, S R; Scarlata, D; Petersen, J

    2011-06-01

    Posttransplant anemia (PTA) is a common, multifactorial condition that has a substantial negative impact on patients' health-related quality of life (HRQOL). Erythropoietin-stimulating agents are an effective treatment for PTA, but there is little research on HRQOL in posttransplant patients. This multicenter, prospective study enrolled adults with PTA (hemoglobin [Hb] < 11.0 g/dL). Subjects (n = 66) received subcutaneous darbepoetin alfa every 2 weeks for 24 weeks. Hb and patient-reported outcomes using the Short Form (SF)-36 questionnaire were assessed. Mean (standard deviation) Hb concentration increased from 9.9 (1.2) g/dL at baseline to 11.7 (1.3) g/dL during the evaluation period (14 to 24 weeks). At baseline, SF-36 scores in all the eight domains were lower (worse) compared with the general population and patients with other chronic conditions. In subjects with baseline Hb < 10 g/dL, SF-36 subscales and component summary scores were lower than in subjects with Hb ? 10 g/dL. Following treatment with darbepoetin alfa, statistically significant improvements were observed for all subjects in physical component summary (0.5 points, P < .001), physical functioning (11.8 points, P = .001), limitations due to physical health (26.5 points, P < .001), bodily pain (7.7 points, P = .01), limitations due to emotional health (15.7 points, P = .01), and vitality (12.8 points, P < .001) from baseline to week 24. Clinically significant improvements (>5 points) were observed in six subscales: physical functioning, limitations due to physical health, limitations due to emotional health, bodily pain, social functioning, and vitality. Darbepoetin alfa in kidney transplant recipients with PTA significantly increased Hb concentrations and improved HRQOL scores. PMID:21693239

  10. The kinetics and apoptotic profile of circulating endothelial cells in autologous hematopoietic stem cell transplantation in patients with lymphoproliferative disorders.

    PubMed

    Szmigielska-Kaplon, Anna; Krawczynska, Anna; Czemerska, Magdalena; Pluta, Agnieszka; Cebula-Obrzut, Barbara; Grzybowska-Izydorczyk, Olga; Wolska, Anna; Szmigielska, Katarzyna; Smolewski, Piotr; Robak, Tadeusz; Wierzbowska, Agnieszka

    2013-09-01

    In neoplastic disorders, endothelial cells take part in tumor progression and also influence the recovery of hematopoiesis after high-dose chemotherapy. Measurements of circulating endothelial cells (CEC), their subsets and kinetics were taken in patients with lymphoid malignancies (37 multiple myeloma, ten lymphoma) during autologous hematopoietic stem cell transplantation (HSCT). CEC were evaluated by four-color flow cytometry at different time points. Additionally levels of angiopoietins 1 and 2 were evaluated by ELISA assay. The baseline number of CECs and their subsets in patients were higher than in the control group. The median CEC number dropped significantly after transplantation (from 9.5/?L to 6.2/?L, p < 0.001). Apoptosis of CECs 24 h after chemotherapy was enhanced in comparison to baseline values (median apoptotic CEC number 4.15/?L vs 3.1/?L; p < 0,001). The time for neutrophil engraftment was shorter for patients with a low apoptotic CEC count at baseline as compared to those with a high apoptotic CEC count (median time to engraftment 13 vs. 16 days respectively, p = 0.04). We observed an adverse correlation of progenitor CEC numbers measured 1 h after transplantation with the time to neutrophil engraftment (r = -0.49, p = 0.008). We also found a negative correlation between the number of CECs originating from microvessels measured 1 h after transplantation, and the time to neutrophil engraftment (r = -0.39, p = 0.04). Baseline angiopoietins 1 and 2 concentration did not influence the post-transplant regeneration time. CEC numbers significantly change during autologous HSCT. Our results suggest that progenitor CECs and CECs derived from microvessels both take part in successful engraftment. PMID:23636312

  11. Diffuse Cystic Lung Disease. Part I.

    PubMed

    Gupta, Nishant; Vassallo, Robert; Wikenheiser-Brokamp, Kathryn A; McCormack, Francis X

    2015-06-15

    The diffuse cystic lung diseases (DCLDs) are a group of pathophysiologically heterogenous processes that are characterized by the presence of multiple spherical or irregularly shaped, thin-walled, air-filled spaces within the pulmonary parenchyma. Although the mechanisms of cyst formation remain incompletely defined for all DCLDs, in most cases lung remodeling associated with inflammatory or infiltrative processes results in displacement, destruction, or replacement of alveolar septa, distal airways, and small vessels within the secondary lobules of the lung. The DCLDs can be broadly classified according to underlying etiology as those caused by low-grade or high-grade metastasizing neoplasms, polyclonal or monoclonal lymphoproliferative disorders, infections, interstitial lung diseases, smoking, and congenital or developmental defects. In the first of a two-part series, we present an overview of the cystic lung diseases caused by neoplasms, infections, smoking-related diseases, and interstitial lung diseases, with a focus on lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis. PMID:25906089

  12. Genetic Diversity of the KIR/HLA System and Susceptibility to Hepatitis C Virus-Related Diseases

    PubMed Central

    De Re, Valli; Caggiari, Laura; De Zorzi, Mariangela; Repetto, Ombretta; Zignego, Anna Linda; Izzo, Francesco; Tornesello, Maria Lina; Buonaguro, Franco Maria; Mangia, Alessandra; Sansonno, Domenico; Racanelli, Vito; De Vita, Salvatore; Pioltelli, Pietro; Vaccher, Emanuela; Beretta, Massimiliano; Mazzaro, Cesare; Libra, Massimo; Gini, Andrea; Zucchetto, Antonella; Cannizzaro, Renato; De Paoli, Paolo

    2015-01-01

    Background The variability in the association of host innate immune response to Hepatitis C virus (HCV) infection requires ruling out the possible role of host KIR and HLA genotypes in HCV-related disorders: therefore, we therefore explored the relationships between KIR/HLA genotypes and chronic HCV infection (CHC) as they relate to the risk of HCV-related hepatocarcinoma (HCC) or lymphoproliferative disease progression. Methods and Findings We analyzed data from 396 HCV-positive patients with CHC (n = 125), HCC (118), and lymphoproliferative diseases (153), and 501 HCV-negative patients. All were HIV and HBV negative. KIR-SSO was used to determine the KIR typing. KIR2DL5 and KIR2DS4 variants were performed using PCR and GeneScan analysis. HLA/class-I genotyping was performed using PCR-sequence-based typing. The interaction between the KIR gene and ligand HLA molecules was investigated. Differences in frequencies were estimated using Fisher’s exact test, and Cochran-Armitage trend test. The non-random association of KIR alleles was estimated using the linkage disequilibrium test. We found an association of KIR2DS2/KIR2DL2 genes, with the HCV-related lymphoproliferative disorders. Furthermore, individuals with a HLA-Bw6 KIR3DL1+ combination of genes showed higher risk of developing lymphoma than cryoglobulinemia. KIR2DS3 gene was found to be the principal gene associated with chronic HCV infection, while a reduction of HLA-Bw4 + KIR3DS1+ was associated with an increased risk of developing HCC. Conclusions Our data highlight a role of the innate-system in developing HCV-related disorders and specifically KIR2DS3 and KIR2D genes demonstrated an ability to direct HCV disease progression, and mainly towards lymphoproliferative disorders. Moreover the determination of KIR3D/HLA combination of genes direct the HCV progression towards a lymphoma rather than an hepatic disease. In this contest IFN-? therapy, a standard therapy for HCV-infection and lymphoproliferative diseases, known to be able to transiently enhance the cytotoxicity of NK-cells support the role of NK cells to counterstain HCV-related and lymphoproliferative diseases. PMID:25700262

  13. Transplantation in the tropics: lessons on prevention and management of tropical infectious diseases.

    PubMed

    Pierrotti, Ligia C; Kotton, Camille N

    2015-07-01

    Tropical infectious diseases (IDs) remain a rare complication in transplant recipients even in tropical settings, but this topic has become increasingly important during the last decade due to multiple factors. Interestingly, non-tropical countries report most of the experiences with tropical diseases. The reported experience from non-endemic regions, however, does not always reflect the experience of endemic areas. Most of the guidelines and recommendations in the literature may not be applicable in tropical settings due to logistical difficulties, cost, and lack of proven benefit. In addition, certain post-transplant prevention measures, as prophylaxis and reducing exposure risk, are not feasible. Nonetheless, risk assessment and post-transplant management of tropical IDs in tropical areas should not be neglected, and clinicians need to have a higher clinical awareness for tropical ID occurring in this population. Herein, we review the more significant tropical ID in transplant patients, focusing on relevant experience reported by tropical settings. PMID:26031964

  14. Sequence Conservation and Differential Expression of Marek's Disease Virus MicroRNAs

    Microsoft Academic Search

    Robin Morgan; Amy Anderson; Erin Bernberg; Sachin Kamboj; Emily Huang; Grace Lagasse; Grace Isaacs; Mark Parcells; Blake C. Meyers; Pamela J. Green; Joan Burnside

    2008-01-01

    Marek's disease virus (MDV), a herpesvirus that causes a lymphoproliferative disorder in chickens, encodes a number of microRNAs derived primarily from two locations in the MDV genome. One cluster of microRNA genes flanks the meq oncogene, and a second cluster is found within the latency-associated transcript (LAT) region. The sequences of MDV microRNAs from a collection of field and reference

  15. Persistent Legionnaire's disease in an adult with hairy cell leukemia successfully treated with prolonged levofloxacin therapy.

    PubMed

    Cunha, Burke A; Munoz-Gomez, Sigridh; Gran, Arthur; Raza, Muhammad; Irshad, Nadia

    2015-01-01

    Legionnaire's disease (LD) manifests most commonly as an atypical community acquired pneumonia (CAP) with systemic extrapulmonary manifestations. Disorders associated with impaired cell mediated immunity (CMI) are particularly predisposed to LD. Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative leukemia associated with decreased CMI. LD has only rarely been reported in HCL. We present a most interesting case of persistent LD in a elderly male with HCL who required prolonged antibiotic therapy. PMID:26021547

  16. Diffuse Cystic Lung Disease. Part II.

    PubMed

    Gupta, Nishant; Vassallo, Robert; Wikenheiser-Brokamp, Kathryn A; McCormack, Francis X

    2015-07-01

    The diffuse cystic lung diseases have a broad differential diagnosis. A wide variety of pathophysiological processes spanning the spectrum from airway obstruction to lung remodeling can lead to multifocal cyst development in the lung. Although lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis are perhaps more frequently seen in the clinic, disorders such as Birt-Hogg-Dubé syndrome, lymphocytic interstitial pneumonia, follicular bronchiolitis, and light-chain deposition disease are increasingly being recognized. Obtaining an accurate diagnosis can be challenging, and management approaches are highly disease dependent. Unique imaging features, genetic tests, serum studies, and clinical features provide invaluable clues that help clinicians distinguish among the various etiologies, but biopsy is often required for definitive diagnosis. In part II of this review, we present an overview of the diffuse cystic lung diseases caused by lymphoproliferative disorders, genetic mutations, or aberrant lung development and provide an approach to aid in their diagnosis and management. PMID:25906201

  17. Monocytes promote tumor cell survival in T-cell lymphoproliferative disorders and are impaired in their ability to differentiate into mature dendritic cells

    PubMed Central

    Wilcox, Ryan A.; Wada, David A.; Ziesmer, Steven C.; Elsawa, Sherine F.; Comfere, Nneka I.; Dietz, Allan B.; Novak, Anne J.; Witzig, Thomas E.; Feldman, Andrew L.; Pittelkow, Mark R.

    2009-01-01

    A variety of nonmalignant cells present in the tumor microenvironment promotes tumorigenesis by stimulating tumor cell growth and metastasis or suppressing host immunity. The role of such stromal cells in T-cell lymphoproliferative disorders is incompletely understood. Monocyte-derived cells (MDCs), including professional antigen-presenting cells such as dendritic cells (DCs), play a central role in T-cell biology. Here, we provide evidence that monocytes promote the survival of malignant T cells and demonstrate that MDCs are abundant within the tumor microenvironment of T cell–derived lymphomas. Malignant T cells were observed to remain viable during in vitro culture with autologous monocytes, but cell death was significantly increased after monocyte depletion. Furthermore, monocytes prevent the induction of cell death in T-cell lymphoma lines in response to either serum starvation or doxorubicin, and promote the engraftment of these cells in nonobese diabetic/severe combined immunodeficient mice. Monocytes are actively recruited to the tumor microenvironment by CCL5 (RANTES), where their differentiation into mature DCs is impaired by tumor-derived interleukin-10. Collectively, the data presented demonstrate a previously undescribed role for monocytes in T-cell lymphoproliferative disorders. PMID:19671921

  18. A novel homozygous Fas ligand mutation leads to early protein truncation, abrogation of death receptor and reverse signaling and a severe form of the autoimmune lymphoproliferative syndrome.

    PubMed

    Nabhani, Schafiq; Hönscheid, Andrea; Oommen, Prasad T; Fleckenstein, Bernhard; Schaper, Jörg; Kuhlen, Michaela; Laws, Hans-Jürgen; Borkhardt, Arndt; Fischer, Ute

    2014-12-01

    We report a novel type of mutation in the death ligand FasL that was associated with a severe phenotype of the autoimmune lymphoproliferative syndrome in two patients. A frameshift mutation in the intracellular domain led to complete loss of FasL expression. Cell death signaling via its receptor and reverse signaling via its intracellular domain were completely abrogated. In vitro lymphocyte proliferation induced by weak T cell receptor stimulation could be blocked and cell death was induced by engagement of FasL in T cells derived from healthy individuals and a heterozygous carrier, but not in FasL-deficient patient derived cells. Expression of genes implicated in lymphocyte proliferation and activation (CCND1, NFATc1, NF-?B1) was increased in FasL-deficient T cells and could not be downregulated by FasL engagement as in healthy cells. Our data thus suggest, that deficiency in FasL reverse signaling may contribute to the clinical lymphoproliferative phenotype of ALPS. PMID:25451160

  19. Validation of the association of TCF7L2 and SLC30A8 gene polymorphisms with post-transplant diabetes mellitus in Asian Indian population

    PubMed Central

    Khan, IImran Ali; Jahan, Parveen; Hasan, Qurratulain; Rao, Pragna

    2015-01-01

    Summary The rs7903146 and rs13266634 polymorphisms in the TCF7L2 and SLC30A8 genes, respectively, have been reported to be associated with type 2 diabetes. However, little is known about the association of these polymorphisms with post-transplant diabetes mellitus (PTDM). To study this linkage, we determined a distribution of allele and genotype frequencies in Asian Indians. 42 PTDM and 98 non-PTDM subjects were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect for rs7903146 and rs13266634 polymorphisms. The clinical details and statistical analysis for PTDM and non-PTDM subjects were recorded. Our results observed higher frequencies of the minor alleles in rs7903146 and rs13266634 polymorphisms in the PTDM group compared to the non-PTDM subjects. The allele frequencies also found to be significantly associated with PTDM (rs7903146: T vs C: OR-2.6; (95%CI: 1.2–5.6); p = 0.01; rs13266634: T vs C: OR-2.0; (95%CI: 1.1–3.4); p = 0.01). These findings suggest that rs7903146 and rs13266634 polymorphisms are associated with PTDM in the Asian Indian population despite a relatively small study group. PMID:25984427

  20. Posttransplant outcome of atypical haemolytic uraemic syndrome in a patient with thrombomodulin mutation: a case without recurrence

    PubMed Central

    Caroti, Leonardo; Di Maria, Lorenzo; Carta, Paolo; Moscarelli, Luciano; Cirami, Calogero; Minetti, Enrico Eugenio

    2015-01-01

    Atypical haemolytic uraemic syndrome (aHUS) is a rare disease characterized by thrombocytopenia, microangiopathic haemolytic anaemia and renal impairment. Mutations in genes encoding inhibitors of the alternative pathway of the complement system are involved in ?50% of the cases. Thrombomodulin (THBD) gene mutations occur in ?3–5% of the cases. The risk of aHUS recurrence after kidney transplantation depends on the complement abnormality involved. In all three cases of THBD mutation reported to date, aHUS recurred after kidney transplantation (KT) with early graft loss. No data exist about therapeutic approaches before kidney transplantation to reduce the risk of recurrence in patients carrying this mutation. Favourable data on the use of eculizumab have been reported, in terms of plasmatherapy withdrawal and renal function recovery in aHUS recurrence after KT. To our knowledge, this case report presents the first case of successful kidney transplantation in a patient with aHUS due to THBD mutation who was treated with a single plasma-exchange immediately before surgery without recurrence of the disease 12 months after transplantation. PMID:26034596

  1. Risk Factors for Chronic Graft-Versus-Host Disease After HLA-Identical Sibling Bone Marrow Transplantation

    Microsoft Academic Search

    Kerry Atkinson; Mary M. Horowitz; Robert Peter Gale; Dirk W. van Bekkum; Eliane Gluckman; Robert A. Good; Niels Jacobsen; Hans-Jochem Kolb; Alfred A. Rimm; Olle Ringden; Ciril Rozman; Kathleen A. Sobocinski

    2010-01-01

    Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of develop- ing chronic GVHD within three years posttransplant was 46% T 3% (95% confidence interval). The most important risk factor for chronic GVHD

  2. A unique description of stage IV extranodal marginal zone lymphoma (EMZL) in an adolescent associated with gamma heavy chain disease.

    PubMed

    Mittal, Nupur; Zhu, Bing; Gaitonde, Sujata; Lu, Yang; Schmidt, Mary Lou

    2015-05-01

    Extranodal Marginal zone lymphoma (EMZL) is a rare, usually localized disease in children. Advanced stage EMZL in adults is considered incurable, with prolonged remissions after chemotherapy. Gamma heavy chain disease (?HCD) is a rare disease of adults associated with lympho-proliferative processes with no comparable reports in children. A case of stage-IV EMZL with ?HCD in an adolescent is discussed including treatment with Bendamustine plus Rituximab. The patient remains disease free 18 months from diagnosis. This case highlights necessity for careful diagnostic work-up to identify indolent lymphomas in children which may respond to less toxic chemotherapy than used for common pediatric lymphomas. PMID:25663537

  3. Multicentric Castleman's Disease, Associated with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Sood, Ruchi; Taylor, Harris C.; Daw, Hamed

    2013-01-01

    The most common cause of a neck mass in young adults is hyperplastic lymphadenopathy consequent to infection and inflammation. Castleman's disease (CD), an unusual benign lymphoproliferative disorder, infrequently causes neck masses. It occurs in unicentric (UCD) and multicentric (MCD) forms and is associated with human immunodeficiency virus (HIV), human herpes virus 8 (HHV-8), and Kaposi's sarcoma. We present the third known association between MCD and previous immune thrombocytopenia in the absence of HIV and HHV-8 infection and review its association with other autoimmune disorders and attendant implications for pathogenesis. Finally, we summarize the current approach to therapy. PMID:24198982

  4. Adult Xanthogranuloma, Reticulohistiocytosis, and Rosai-Dorfman Disease.

    PubMed

    Chisolm, Sarah S; Schulman, Joshua M; Fox, Lindy P

    2015-07-01

    Adult xanthogranuloma presents most commonly as an orange-tan firm solitary nodule with no systemic manifestations. Recently, some cases have been reported in conjunction with lymphoproliferative disorders. Adult reticulohistiocytosis classically presents as red to yellow-red dermal nodules. In the multicentric form, lesions have a predilection for hands and elbows, with a classic coral bead periungual presentation, and are often associated with symmetric erosive arthritis, particularly of the hands and wrists. The presentation and course of Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, can vary. The classic presentation is extensive, painless bilateral cervical lymphadenopathy, but some cases have been entirely extranodal. PMID:26143426

  5. Immunological analysis of the skin in graft versus host disease.

    PubMed Central

    Lampert, I A; Janossy, G; Suitters, A J; Bofill, M; Palmer, S; Gordon-Smith, E; Prentice, H G; Thomas, J A

    1982-01-01

    Immunohistochemical analysis was performed on skin biopsies from patients suffering from graft versus host disease (GVHD) following bone marrow transplantation for aplastic anaemia and leukaemia. Lymphoid cells infiltrating the skin were exclusively T cells with the OKT8+ phenotype and these are probably cytotoxic T cells. Langerhans cells were reduced in number in all specimens and a variable number of HLA-DR positive macrophages were seen in the dermis. In several cases HLA-DR antigens were expressed on keratinocytes. These results show consistent features which may help discriminate rashes in the skin in the post-transplant period. Images Fig. 1 PMID:6756725

  6. Siltuximab: a new option for the management of Castleman's disease.

    PubMed

    Barquero, N

    2015-01-01

    Castleman's disease is a rare lymphoproliferative disorder the underlying mechanism of which remains unclear. However, interleukin-6 (IL-6) may play a role in the pathogenesis of the disease. Blockade of the IL-6 pathway has been explored in multiple preclinical and clinical studies with promising results for the treatment of different types of cancer and Castleman's disease. Siltuximab is a human/murine chimeric immunoglobulin G1kappa (IgG1kappa) monoclonal antibody against human IL-6. It binds to IL-6 neutralizing its biological activity. Recent phase II clinical studies in patients with multicentric Castleman's disease have shown the efficacy and safety of siltuximab in patients with this condition. Results from this study led to the recent approval of siltuximab for the treatment of Castleman's disease by the FDA and EMA. PMID:25685858

  7. Pre-transplant angiotensin II type 1receptor antibodies: a risk factor for decreased kidney graft function in the early post-transplant period?

    PubMed

    Hernández-Méndez, Erick Alejandro; Arreola-Guerra, José Manuel; Morales-Buenrostro, Luis E; Ramírez, Julia B; Calleja, Said; Castelán, Natalia; Salcedo, Isaac; Vilatobá, Mario; Contreras, Alan G; Gabilondo, Bernardo; Granados, Julio; Alberú, Josefina

    2014-01-01

    Angiotensin II type 1 receptor antibodies (AT1Rab) are associated to a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and BPAR during the 1st year post-transplant (PT) in adult kidney transplant recipients (KTR), between 03/2009 and 08/2012. Pre-KT sera were screened for AT1Rab (ELISA) and HLA-DSA (Luminex). Three groups were analyzed: AT1Rab only (n = 13); HLA-DSA only (n = 8); and no AT1Rab or HLA-DSA (n = 90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. KTR with AT1Rab had a lower mean eGFR (20 mL/min/1.73m2) when compared to KTR with no Abs at 12 months. The significant difference in eGFR was observed since the 1st month PT. Multivariate analysis showed 4 factors independently and significantly associated with eGFR at 12mos PT: BPAR (-18.7 95%, CI -28.2 to -9.26, p<0.001), AT1Rab (-10.51, CI -20.9 to -0.095, p = 0.048), donor age (-0.42, CI -0.75 to -0.103 p = 0.010), and recipient age (-0.36, CI -0.67 to -0.048, p = 0.024). In this study AT1Rab in pre-transplant sera from KTR, was an independent and significant risk factor contributing to a lower eGFR 12 months. PT. This finding deserves to be confirmed in a larger KTR population. PMID:25695237

  8. Peri-operative kidney injury and long-term chronic kidney disease following orthotopic heart transplantation in children.

    PubMed

    Hoskote, Aparna; Burch, Michael

    2015-06-01

    Significant advances in cardiac intensive care including extracorporeal life support have enabled children with complex congenital heart disease and end-stage heart failure to be supported while awaiting transplantation. With an increasing number of survivors after heart transplantation in children, the complications from long-term immunosuppression, including renal insufficiency, are becoming more apparent. Severe renal dysfunction after heart transplant is defined by a serum creatinine level?>2.5 mg/dL (221 ?mol/L), and/or need for dialysis or renal transplant. The degree of renal dysfunction is variable and is progressive over time. About 3-10 % of heart transplant recipients will go on to develop severe renal dysfunction within the first 10 years post-transplantation. Multiple risk factors for chronic kidney disease post-transplant have been identified, which include pre-transplant worsening renal function, recipient demographics and morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin inhibitors. Renal insufficiency increases the risk of post-transplant morbidity and mortality. Hence, screening for renal dysfunction pre-, peri- and post-transplantation is important. Early and timely detection of renal insufficiency may help minimize renal insults, and allow prompt implementation of renoprotective strategies. Close monitoring and pre-emptive management of renal dysfunction is an integral aspect of peri-transplant and subsequent post-transplant long-term care. PMID:25115875

  9. EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma*

    PubMed Central

    Pfaltz, Katrin; Vermeer, Maarten H.; Cozzio, Antonio; Ortiz-Romero, Pablo L.; Bagot, Martine; Olsen, Elise; Kim, Youn H.; Dummer, Reinhard; Pimpinelli, Nicola; Whittaker, Sean; Hodak, Emmilia; Cerroni, Lorenzo; Berti, Emilio; Horwitz, Steve; Prince, H. Miles; Guitart, Joan; Estrach, Teresa; Sanches, José A.; Duvic, Madeleine; Ranki, Annamari; Dreno, Brigitte; Ostheeren-Michaelis, Sonja; Knobler, Robert; Wood, Gary; Willemze, Rein

    2011-01-01

    Primary cutaneous CD30+ lymphoproliferative disorders (CD30+ LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30+ LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30+ LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30+ LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30+ LPDs. PMID:21841159

  10. Nodal and extranodal plasmacytomas expressing immunoglobulin A: an indolent lymphoproliferative disorder with a low risk of clinical progression

    PubMed Central

    Shao, Haipeng; Xi, Liqiang; Raffeld, Mark; Pittaluga, Stefania; Dunleavy, Kieron; Wilson, Wyndham; Spector, Nelson; Milito, Cristiane; Morais, Jose Carlos; Jaffe, Elaine S.

    2010-01-01

    Plasmacytomas expressing immunoglobulin A are rare and not well characterized. In this study, nine cases of IgA-positive plasmacytomas presenting in lymph node and three in extranodal sites were analyzed by morphology, immunohistochemistry, and PCR examination of immunoglobulin heavy and kappa light chain genes. Laboratory features were correlated with clinical findings. There were seven males and five females; age range was 10 to 66 years (median, 32 years). Six of the patients were younger than 30-years-old, five of whom had nodal disease. 67% (6/9) of the patients with nodal disease had evidence of immune system dysfunction, including human immunodeficiency virus (HIV) infection, T-cell deficiency, autoantibodies, arthritis, Sjögren’s syndrome, and decreased B-cells. An IgA M-spike was detected in 6/11 cases, and the M-protein was nearly always less than 30 g/L. All patients had an indolent clinical course without progression to plasma cell myeloma. Histologically, IgA plasmacytomas showed an interfollicular or diffuse pattern of plasma cell infiltration. The plasma cells were generally of mature Marschalko type with little or mild pleomorphism and exclusive expression of monotypic IgA. There was an equal expression of kappa and lambda light chains (ratio 6:6). Clonality was demonstrated in 9 of 12 cases: by PCR in 7 cases, by cytogenetic analysis in 1 case, and by immunofixation in 1 case. Clonality did not correlate with pattern of lymph node infiltration. Our results suggest that IgA plasmacytomas may represent a distinct form of extramedullary plasmacytoma characterized by younger age at presentation, frequent lymph node involvement and low risk of progression to plasma cell myeloma. PMID:20871216

  11. Multicentric Castleman Disease in an HHV8-Infected Child Born to Consanguineous Parents With Systematic Review

    PubMed Central

    Moshous, Despina; Cassar, Olivier; Reguerre, Yves; Byun, Minji; Pedergnana, Vincent; Canioni, Danielle; Gessain, Antoine; Oksenhendler, Eric; Fieschi, Claire; Mahlaoui, Nizar; Rivičre, Jean-Pierre; Herbigneaux, Rose-Marie; Muszlak, Matthias; Arnaud, Jean-Pierre; Fischer, Alain; Picard, Capucine; Blanche, Stéphane; Plancoulaine, Sabine

    2012-01-01

    Childhood multicentric Castleman disease (MCD) is a rare and unexplained lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected child, born to consanguineous Comorian parents, who displayed isolated MCD in the absence of any known immunodeficiency. We also systematically review the clinical features of the 32 children previously reported with isolated and unexplained MCD. The characteristics of this patient and the geographic areas of origin of most previous cases suggest that pediatric MCD is associated with HHV-8 infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood may result from inborn errors of immunity to HHV-8 infection. PMID:22157133

  12. Rituximab for prevention and treatment of graft-versus-host disease.

    PubMed

    Kharfan-Dabaja, Mohamed A; Cutler, Corey S

    2011-05-01

    Growing understanding of the important role of B lymphocytes in alloreactivity has paved the way for evaluating anti-B cell therapy with rituximab in patients undergoing allogeneic hematopoietic cell transplantation. Data suggesting a beneficial reduction in incidence and severity of acute graft-versus-host disease (GVHD) are limited to non-randomized studies from single institutions using higher than conventional doses of rituximab. Additionally, rituximab is used as an effective treatment of corticosteroid-refractory chronic GVHD with good responses, particularly in cases of dermatologic and mucosal involvement. Post-transplant administration of rituximab appears to reduce the rate of chronic GVHD in preliminary studies. PMID:21547615

  13. Concomitant Castleman's disease and sarcoidosis.

    PubMed

    Rice, Brenda L; Farver, Carol F; Pohlman, Brad; Burkey, Brian B; Parambil, Joseph G

    2011-03-01

    Castleman's disease (CD) is an atypical lymphoproliferative disorder characterized by hyperplasia of lymphoid tissue that may develop at a single site or throughout the body. This disorder has frequently been associated with several systemic syndromes, including human immunodeficiency virus infection, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome and various connective tissue diseases. However, there have been no previously reported cases of concomitant sarcoidosis and CD. In this report, the authors describe a young woman with an enlarging neck mass, biopsy of which showed histopathological features consistent with the hyaline vascular type of CD along with the presence of non-necrotizing granulomas and was deemed unresectable due to encasement of vital neural and vascular structures. Further studies revealed hypermetabolic generalized lymphadenopathy with pulmonary perilymphatic nodules. Bronchoscopic investigations demonstrated the presence of non-necrotizing granulomas within the lung parenchyma and mediastinal lymph nodes, a CD4(+) T-lymphocyte predominant bronchoalveolar lavage and an elevated CD4/CD8 ratio consistent with a concomitant diagnosis of sarcoidosis. Institution of immunosuppression with prednisone and methotrexate led to reduction in size of the neck mass that allowed radical curative resection of the CD. PMID:21326077

  14. Regional Differences in Recipient Waitlist Time and Pre- and Post-Transplant Mortality After the 2006 United Network for Organ Sharing Policy Changes in the Donor Heart Allocation Algorithm

    PubMed Central

    Schulze, P. Christian; Kitada, Shuichi; Clerkin, Kevin; Jin, Zhezhen; Mancini, Donna M.

    2014-01-01

    Objectives This study examined the impact of the United Network for Organ Sharing (UNOS) policy changes for regional differences in waitlist time and mortality before and after heart transplantation. Background The 2006 UNOS thoracic organ allocation policy change was implemented to allow for greater regional sharing of organs for heart transplantation. Methods We analyzed 36,789 patients who were listed for heart transplantation from January 1999 through April 2012. These patients were separated into 2 eras centered on the July 12, 2006 UNOS policy change. Pre- and post-transplantation characteristics were compared by UNOS regions. Results Waitlist mortality decreased nationally (up to 180 days: 13.3% vs. 7.9% after the UNOS policy change, p < 0.001) and within each region. Similarly, 2-year post-transplant mortality decreased nationally (2-year mortality: 17.3% vs. 14.6%; p < 0.001) as well as regionally. Waitlist time for UNOS status 1A and 1B candidates increased nationally 17.8 days on average (p < 0.001) with variability between the regions. The greatest increases were in Region 9 (59.2-day increase, p < 0.001) and Region 4 (41.2-day increase, p < 0.001). Although the use of mechanical circulatory support increased nearly 2.3-fold nationally in Era 2, significant differences were present on a regional basis. In Regions 6, 7, and 10, nearly 40% of those transplanted required left ventricular assist device bridging, whereas only 19.6%, 22.3%, and 15.5% required a left ventricular assist device in regions 3, 4, and 5, respectively. Conclusions The 2006 UNOS policy change has resulted in significant regional heterogeneity with respect to waitlist time and reliance on mechanical circulatory support as a bridge to transplantation, although overall both waitlist mortality and post-transplant survival are improved. PMID:24720925

  15. [Hibernoma and cervical rib: two rare diseases, the same manifestation].

    PubMed

    Antunes, J; Santos, S; Andrade, N; Simőes, F; Salgado, C

    2013-07-01

    The hibernoma is a rare benign tumor of soft tissue, derived from remnants of fetal brown adipose tissue. A cervical rib is a supernumerary or accessory rib derived from the 7th cervical vertebra. CLINCAL CASE: 2-year-old girl, previously healthy, referenced to Pediatrics consultation, for left supraclavicular mass. No history of infectious diseases or systemic symptoms. At exam presented mass in supraclavicular left region, 1.5 to 2 cm in diameter, hard, mobile, non-adherent to the deep planes. Laboratory tests exclude an infectious or lymphoproliferative disease. In cervical radiograph we observed bilateral cervical ribs. Cervical ultrasound revealed calcified nodule 0.8 cm, compatible with calcified adenopathy. Biopsy was performed and histology revealed a hibernoma, which was completely removed surgically. This case illustrates the association of two diagnoses, uncommon in children. These were made during the investigation of lymphadenopathies, a frequent reason for pediatrics consultation. PMID:24482907

  16. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning

    PubMed Central

    Kahl, Christoph; Storer, Barry E.; Sandmaier, Brenda M.; Mielcarek, Marco; Maris, Michael B.; Blume, Karl G.; Niederwieser, Dietger; Chauncey, Thomas R.; Forman, Stephen J.; Agura, Edward; Leis, Jose F.; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A.; McSweeney, Peter A.; Wade, James C.; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A.; Maloney, David G.

    2007-01-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m2; n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT. PMID:17595333

  17. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

    PubMed

    Kahl, Christoph; Storer, Barry E; Sandmaier, Brenda M; Mielcarek, Marco; Maris, Michael B; Blume, Karl G; Niederwieser, Dietger; Chauncey, Thomas R; Forman, Stephen J; Agura, Edward; Leis, Jose F; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A; McSweeney, Peter A; Wade, James C; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A; Maloney, David G; Storb, Rainer

    2007-10-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m(2); n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT. PMID:17595333

  18. A multigene array for measurable residual disease detection in AML patients undergoing SCT.

    PubMed

    Goswami, M; McGowan, K S; Lu, K; Jain, N; Candia, J; Hensel, N F; Tang, J; Calvo, K R; Battiwalla, M; Barrett, A J; Hourigan, C S

    2015-05-01

    AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ-PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994-2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ-PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection. PMID:25665046

  19. A multigene array for measurable residual disease detection in AML patients undergoing SCT

    PubMed Central

    Goswami, M; McGowan, K S; Lu, K; Jain, N; Candia, J; Hensel, N F; Tang, J; Calvo, K R; Battiwalla, M; Barrett, A J; Hourigan, C S

    2015-01-01

    AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ–PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994–2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ–PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection. PMID:25665046

  20. Recurrence of diabetic kidney disease in a type 1 diabetic patient after kidney transplantation.

    PubMed

    Nyumura, Izumi; Honda, Kazuho; Babazono, Tetsuya; Horita, Shigeru; Murakami, Toru; Fuchinoue, Shohei; Uchigata, Yasuko

    2015-07-01

    Post-transplant hyperglycaemia of diabetic patients may cause recurrent diabetic kidney disease (DKD) in kidney allografts. We report a patient with slowly progressive DKD with calcineurin inhibitor toxicity (CNI) toxicity after the kidney transplantation. A 28-year-old female with type 1 diabetes mellitus underwent successful kidney transplantation from her mother in April 2003, and the kidney graft survived for more than 10 years. She was treated with combined immunosuppressive therapy consisting of cyclosporine and mycophenolate mofetil. After transplantation, she continued to take insulin injection four times per day, but her glycosylated haemoglobin (HbA1c) was above 10%. Protocol allograft kidney biopsies performed 5 and 10 years after transplantation revealed the recurrence of slowly progressive diabetic kidney disease. In addition, arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity (CNI) was detected with progression. Post-transplant hyperglycaemia causes recurrent diabetic kidney disease (DKD) in kidney allografts, but its progression is usually slow. For long-term management, it is important to prevent the progression of the calcineurin inhibitor arteriolopathy, as well as maintain favourable glycaemic control. PMID:26031596

  1. Pre-and-post transplant considerations in patients with nonalcoholic fatty liver disease

    PubMed Central

    Khullar, Vikas; Dolganiuc, Angela; Firpi, Roberto J

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is currently the third most common indication for liver transplantation in the United States. With the growing incidence of obesity, NAFLD is expected to become the most common indication for liver transplantation over the next few decades. As the number of patients who have undergone transplantation for NAFLD increases, unique challenges have emerged in the management and long-term outcomes in patients. Risk factors such as obesity, hypertension, diabetes, and hyperlipidemia continue to play an important role in the pathogenesis of the disease and its recurrence. Patients who undergo liver transplantation for NAFLD have similar long-term survival as patients who undergo liver transplantation for other indications. Research shows that post-transplantation recurrence of NAFLD is commonplace with some patients progressing to recurrent non-alcoholic steatohepatitis and cirrhosis. While treatment of comorbidities is important, there is no consensus on the management of modifiable risk factors or the role of pharmacotherapy and immunosuppression in patients who develop recurrent or de novo NAFLD post-transplant. This review provides an outline of NAFLD as indication for liver transplantation with a focus on the epidemiology, pathophysiology and risk factors associated with this disease. It also provides a brief review on the pre-transplant considerations and post-transplant factors including patient characteristics, role of obesity and metabolic syndrome, recurrence and de novo NAFLD, outcomes post-liver transplantation, choice of medications, and options for immunosuppression. PMID:25032097

  2. Respiratory Syncytial Virus in Hematopoietic Cell Transplant Recipients: Factors Determining Progression to Lower Respiratory Tract Disease

    PubMed Central

    Kim, Yae-Jean; Guthrie, Katherine A.; Waghmare, Alpana; Walsh, Edward E.; Falsey, Ann R.; Kuypers, Jane; Cent, Anne; Englund, Janet A.; Boeckh, Michael

    2014-01-01

    Background.?Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD. Methods.?This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI. Results.?In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ?100/mm3 at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm3 at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression. Conclusions.?Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted. PMID:24368837

  3. Primary immunodeficiencies predisposed to Epstein-Barr virus-driven haematological diseases.

    PubMed

    Parvaneh, Nima; Filipovich, Alexandra H; Borkhardt, Arndt

    2013-09-01

    Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, maintains lifelong subclinical persistent infections in humans. In the circulation, EBV primarily infects the B cells, and protective immunity is mediated by EBV-specific cytotoxic T cells (CTLs) and natural killer (NK) cells. However, EBV has been linked to several devastating diseases, such as haemophagocytic lymphohistiocytosis (HLH) and lymphoproliferative diseases in the immunocompromised host. Some types of primary immunodeficiencies (PIDs) are characterized by the development of EBV-associated complications as their predominant clinical feature. The study of such genetic diseases presents an ideal opportunity for a better understanding of the biology of the immune responses against EBV. Here, we summarize the range of PIDs that are predisposed to EBV-associated haematological diseases, describing their clinical picture and pathogenetic mechanisms. PMID:23758097

  4. General anesthesia in a patient with multicentric Castleman's disease: a case report

    PubMed Central

    Huh, In Young; Lee, Sang Hyun; Kim, An Suk; Park, Se Hun; Kim, Dae-Young

    2015-01-01

    Castleman's disease (CD) is a rare lymphoproliferative disorder of undetermined etiology. Unicentric Castleman's disease is confined to a single lymph node; it is usually asymptomatic though sometimes has local manifestations related to mass effects. In contrast, multicentric Castleman's disease (MCD) typically presents with lymphoid hyperplasia at multiple sites; it is associated with systemic symptoms and abnormal laboratory findings, with a less favorable prognosis. In case of anesthesia in CD, an exhaustive preanesthetic evaluation is essential to identify associated clinical manifestations which may influence the management of the anesthesia. Perioperative careful monitoring and proper anesthetic management are both important. We report a case of general anesthesia with anesthetic management in a patient with MCD that has not been documented in the literature.

  5. Epstein–Barr Virus, the Immune System, and Associated Diseases

    PubMed Central

    Chen, Mei-Ru

    2011-01-01

    Host immune system is designed (or evolved) to fight against different pathogens. Many viruses infect the immune cells for the propagation of new progenies, thus the infection may modulate the host immune homeostasis. It has been more than 45 years since the discovery of Epstein–Barr virus (EBV) from a Burkitt's lymphoma derived cell line. The ability of EBV to transform primary B cells in vitro leads to the suggestion for its oncogenic potential. However, except the clear understanding of the role of EBV in post-transplantation lymphoproliferative disease, it remains ambiguous why such a ubiquitous virus causes malignant diseases only in a very small subset of individuals. Possible explanation is that EBV may cooperate with other environmental and host genetic factors and lead to the development of EBV associated neoplastic diseases. In addition to infecting B cells, recent studies revealed that EBV may impact host immune system more broadly than previously thought, for example the development of regulatory NKT subsets. Instead of an intensive review, this article aims to provide a linkage to recent advances on the interplay between EBV and host immune system and to inspire further studies on EBV related diseases, especially autoimmune diseases. PMID:21687403

  6. Clonal disease of natural killer large granular lymphocytes in Taiwan.

    PubMed

    Chou, W C; Chiang, I P; Tang, J L; Su, I J; Huang, S Y; Chen, Y C; Liu, M C; Lee, F Y; Wang, C H; Shen, M C; Chuang, S M; Tien, H F

    1998-12-01

    Lymphoproliferative diseases of large granular lymphocytes (LDGL) may arise from either CD3+ T cells or CD3- natural killer (NK) cells. LDGL with clonal proliferation of large granular lymphocytes (LGL) is defined as LGL leukaemia. The number of patients with NK-LGL leukaemia reported is limited and the pathogenesis of the disease is not yet clear. From 1991 to 1998 six patients with cytogenetically proved clonal disease of NK-LGL were identified in our institute. All were seropositive for Epstein-Barr virus (EBV). EBV RNA or DNA could be detected in LGL from four patients by EBV in situ hybridization or Southern blot analysis. Most patients ran an aggressive clinical course and five died of the disease. Nonrandom clonal chromosomal abnormalities, including duplication of 1q, rearrangement at 3q and loss of chromosomes Y, 13 or 10, were noted in the six patients from this study and in eight from the literature. The implications of these recurrent cytogenetic aberrations in the development and progression of the disease deserve further studies. PMID:9886330

  7. [Autologous stem cell transplantation for autoimmune diseases: recommendations from the SFGM-TC].

    PubMed

    Farge, D; Terriou, L; Badoglio, M; Cras, A; Desreumaux, P; Hadj-Khelifa, S; Marjanovic, Z; Moisan, A; Dulery, R; Faucher, C; Hij, A; Martin, T; Vermersch, P; Yakoub-Agha, I

    2014-08-01

    Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients. PMID:25017794

  8. End-stage renal disease in India and Pakistan: burden of disease and management issues.

    PubMed

    Sakhuja, Vinay; Sud, Kamal

    2003-02-01

    In the absence of national registries, no reliable data are available on the incidence and prevalence of end-stage renal disease (ESRD) in India and Pakistan. The incidence of ESRD is likely to be higher than that reported from the developed world, with chronic glomerulonephritis being the most common cause, accounting for more than one third of patients, while diabetic nephropathy accounts for about one fourth of all patients in India. Patients are generally younger (mean age 42 years) at the time of detection of ESRD and two-thirds first see a nephrologist after they have reached end stage. Treatment of ESRD is a low priority for the cash-strapped public hospitals and in the absence of health insurance plans, less than 10% of all patients receive any kind of renal replacement therapy. The vast majority of patients starting hemodialysis die or stop treatment because of cost constraints within the first three months, and less than 2% patients are started on ambulatory peritoneal dialysis. Although renal transplantation is the cheapest option, only about 5% of all patients with ESRD end up having a transplant. Living related donor transplants constitute 30 to 40% of all transplants in India, but there is a conspicuous gender bias with female donors donating kidneys for their male relatives. Cadaveric transplantation has yet to pick up and accounts for less than 2% of all transplants. The enactment of legislation to regulate renal transplantation in India has not been able to prevent unrelated (paid) donor transplants, which constitute 60 to 70% of all renal transplants. Cyclosporine, azathioprine and prednisolone continue to be the backbone of post-transplant immunosuppression, with cyclosporine being stopped in a significant proportion at one year post-transplant to cut down costs. Increasing awareness of renal disease amongst the population and general practitioners could result in early diagnosis of chronic renal failure and give opportunity for preventive strategies to delay the onset of ESRD. Preemptive transplantation and use of generic cyclosporine can help bring down the costs of treatment. Innovative and affordable health insurance policies can also increase the number of patients who receive effective treatment for ESRD in these two countries. PMID:12864888

  9. Clinical diagnosis of metabolic syndrome: predicting new-onset diabetes, coronary heart disease, and allograft failure late after kidney transplant.

    PubMed

    Israni, Ajay K; Snyder, Jon J; Skeans, Melissa A; Kasiske, Bertram L

    2012-07-01

    Metabolic syndrome is associated with coronary heart disease (CHD) and new-onset diabetes after kidney transplant (NODAT). Using data collected from transplant centers worldwide for the Patient Outcomes in Renal Transplantation study, we examined associations of metabolic syndrome (n = 2253 excluding recipients with diabetes pretransplant), CHD (n = 2253), and NODAT (n = 1840 further excluding recipients with diabetes in the first year post-transplant), with the primary outcome of allograft failure. We assessed risk factors associated with secondary outcomes of metabolic syndrome, NODAT, and CHD after adjusting for type of baseline immunosuppression and transplant center effects. Metabolic syndrome prevalence was 39.8% at 12-24 months post-transplant and 35.4% at 36-48 months. Metabolic syndrome was independently associated with NODAT (hazard ratio 3.46, 95% confidence interval 2.40-4.98, P < 0.0001), CHD (2.03, 1.16-3.52, P = 0.013), and allograft failure (1.36, 1.03-1.79, P = 0.028). Allograft failure occurred in 218 patients (14.6%). After adjustment for metabolic syndrome, NODAT (1.63, 1.18-2.24, P = 0.003) and CHD (5.48, 3.27-9.20, P < 0.0001) remained strongly associated with increased risk of allograft failure. Metabolic syndrome, NODAT, and CHD are risk factors for allograft failure. NODAT and CHD are risk factors for allograft failure, independent of metabolic syndrome. PMID:22548293

  10. Overexpression of Activation-Induced Cytidine Deaminase in MTX- and Age-Related Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorders of the Head and Neck.

    PubMed

    Kikuchi, Kentaro; Ishige, Toshiyuki; Ide, Fumio; Ito, Yumi; Saito, Ichiro; Hoshino, Miyako; Inoue, Harumi; Miyazaki, Yuji; Nozaki, Tadashige; Kojima, Masaru; Kusama, Kaoru

    2015-01-01

    Recent research has shown that activation-induced cytidine deaminase (AID) triggers somatic hypermutation and recombination, in turn contributing to lymphomagenesis. Such aberrant AID expression is seen in B-cell leukemia/lymphomas, including Burkitt lymphoma which is associated with c-myc translocation. Moreover, Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) increases genomic instability through early growth transcription response-1 (Egr-1) mediated upregulation of AID in B-cell lymphoma. However, few clinicopathological studies have focused on AID expression in lymphoproliferative disorders (LPDs). Therefore, we conducted an immunohistochemical study to investigate the relationship between AID and LMP-1 expression in LPDs (MTX-/Age-related EBV-associated), including diffuse large B-cell lymphomas (DLBCLs). More intense AID expression was detected in LPDs (89.5%) than in DLBCLs (20.0%), and the expression of LMP-1 and EBER was more intense in LPDs (68.4% and 94.7%) than in DLBCLs (10.0% and 20.0%). Furthermore, stronger Egr-1 expression was found in MTX/Age-EBV-LPDs (83.3%) than in DLBCLs (30.0%). AID expression was significantly constitutively overexpressed in LPDs as compared with DLBCLs. These results suggest that increased AID expression in LPDs may be one of the processes involved in lymphomagenesis, thereby further increasing the survival of genetically destabilized B-cells. AID expression may be a useful indicator for differentiation between LPDs and DLBCLs. PMID:25834572

  11. Overexpression of Activation-Induced Cytidine Deaminase in MTX- and Age-Related Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorders of the Head and Neck

    PubMed Central

    Kikuchi, Kentaro; Ishige, Toshiyuki; Ide, Fumio; Ito, Yumi; Saito, Ichiro; Hoshino, Miyako; Inoue, Harumi; Miyazaki, Yuji; Nozaki, Tadashige; Kojima, Masaru; Kusama, Kaoru

    2015-01-01

    Recent research has shown that activation-induced cytidine deaminase (AID) triggers somatic hypermutation and recombination, in turn contributing to lymphomagenesis. Such aberrant AID expression is seen in B-cell leukemia/lymphomas, including Burkitt lymphoma which is associated with c-myc translocation. Moreover, Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) increases genomic instability through early growth transcription response-1 (Egr-1) mediated upregulation of AID in B-cell lymphoma. However, few clinicopathological studies have focused on AID expression in lymphoproliferative disorders (LPDs). Therefore, we conducted an immunohistochemical study to investigate the relationship between AID and LMP-1 expression in LPDs (MTX-/Age-related EBV-associated), including diffuse large B-cell lymphomas (DLBCLs). More intense AID expression was detected in LPDs (89.5%) than in DLBCLs (20.0%), and the expression of LMP-1 and EBER was more intense in LPDs (68.4% and 94.7%) than in DLBCLs (10.0% and 20.0%). Furthermore, stronger Egr-1 expression was found in MTX/Age-EBV-LPDs (83.3%) than in DLBCLs (30.0%). AID expression was significantly constitutively overexpressed in LPDs as compared with DLBCLs. These results suggest that increased AID expression in LPDs may be one of the processes involved in lymphomagenesis, thereby further increasing the survival of genetically destabilized B-cells. AID expression may be a useful indicator for differentiation between LPDs and DLBCLs. PMID:25834572

  12. Expanded infectious diseases screening program for Hispanic transplant candidates.

    PubMed

    Fitzpatrick, M A; Caicedo, J C; Stosor, V; Ison, M G

    2010-08-01

    Most guidelines for pre-transplant screening recommend enhanced screening among patients with potential exposure to such pathogens as Strongyloides stercoralis and Trypanosoma cruzi, the cause of Chagas disease. The incidence of these diseases in the Hispanic immigrant population has not been extensively studied. Transplant candidates who were evaluated by our program's Hispanic Transplant Program were referred for expanded infectious disease screening including Mycobacterium tuberculosis, S. stercoralis, Leishmania, and T. cruzi. Between December 2006 and December 2008, 83 patients were screened. Most were from Mexico but we also screened patients from Ecuador, Puerto Rico, and Peru. Most patients lived in urban locations before moving to the United States. Latent tuberculosis infection (LTBI) was found in 20%, and 6.7% had serologic evidence of S. stercoralis infection. These patients underwent treatment of latent infection without difficulty. To date, 14 patients have undergone living-donor kidney transplantation. Two of these patients had positive Leishmania titers and are being followed clinically, 1 was treated for S. stercoralis, and 2 were treated for LTBI pre-transplant. All have done well without evidence of screened pathogens an average of 348 days (range 65-766 days) post transplant. Expanded screening identifies endemic infections in the Hispanic immigrant population that can be treated before transplant, thereby minimizing post-transplant infectious complications. PMID:20534036

  13. Elevated level of HSPA1L mRNA correlates with graft-versus-host disease.

    PubMed

    Atarod, Sadaf; Turner, Brie; Pearce, Kim Frances; Ahmed, Shaheda S; Norden, Jean; Bogunia-Kubik, Katarzyna; Wang, Xiao-Nong; Collin, Matthew; Dickinson, Anne Mary

    2015-06-01

    Graft-versus-host disease (GVHD) can be a fatal complication of allogeneic stem cell transplantation (allo-HSCT). GVHD can be classified as acute (aGVHD: up to 100days) or chronic (cGVHD: after 100days) based on the time-point of disease occurrence. At present there are a limited number of biomarkers available for use in the clinic. Thus, the aim of this research was to evaluate the biomarker potential of the extensively studied Heat Shock Protein 70 family members (HSPA1A/HSPA1B and HSPA1L) at the messenger RNA (mRNA) level in acute and cGVHD patient cohorts. In the skin biopsies, HSPA1L mRNA expression was lower in patients with severe aGVHD (grades II-III) when compared to those with none or low grade aGVHD (grades 0-I) and normal controls. In whole blood, HSPA1L mRNA expression level was significantly (p=0.008) up-regulated at 28days post-transplant in cGVHD patients with a significant area under the curve (AUC=0.773). In addition, HSPA1B expression in whole blood was significantly higher at 3months post-transplant in both the aGVHD grade II-III (p=0.012) and cGVHD (p=0.027) patients. Our initial results in this small cohort show that quantifying HSPA1L mRNA expression in the whole blood of allo-HSCT patients at day 28 post-allo-HSCT may be a useful predictive biomarker for cGVHD. PMID:25680846

  14. Refsum Disease

    MedlinePLUS

    ... Organizations What is Refsum Disease? Adult Refsum disease (ARD) is a rare genetic disease that causes weakness ... neuropathy). Due to a genetic abnormality, people with ARD disease lack the enzyme in peroxisomes that break ...

  15. Fabry's Disease

    MedlinePLUS

    NINDS Fabry Disease Information Page Table of Contents (click to jump to sections) What is Fabry Disease? Is there any ... is being done? Clinical Trials Organizations What is Fabry Disease? Fabry disease is caused by the lack of ...

  16. Graves' Disease

    MedlinePLUS

    ... information Autoimmune diseases fact sheet Diabetes fact sheet Hashimoto's disease fact sheet Illnesses and disabilities Lupus fact ... of overactive thyroid. It is closely related to Hashimoto's disease, another autoimmune disease affecting the thyroid. Return ...

  17. Behcet's Disease

    MedlinePLUS

    NINDS Behcet's Disease Information Page Table of Contents (click to jump to sections) What is Behcet's Disease? Is there any ... Trials Organizations Additional resources from MedlinePlus What is Behcet's Disease? Behcet's disease is a rare, chronic inflammatory disorder. ...

  18. Lentil Diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Major lentil diseases around the world have been described and reviewed. The major diseases include Ascochyta blight, Fusarium wilt, Botrytis Gray Mold, Lentil rust, Stemphylium blight, Anthracnose, and virus diseases. The management practices for these diseases are also presented....

  19. Crohn's disease

    MedlinePLUS

    Inflammatory bowel disease - Crohn's disease; Regional enteritis; Ileitis; Granulomatous ileocolitis; IBD- Crohn's disease ... Pa: Saunders Elsevier; 2010:chap 111. Lichenstein GR. Inflammatory bowel disease. In: Goldman L, Schafer AI, eds. Cecil Medicine . ...

  20. Ribbing disease

    PubMed Central

    Mukkada, Philson J; Franklin, Teenu; Rajeswaran, Rangasami; Joseph, Santhosh

    2010-01-01

    Ribbing disease is a rare sclerosing dysplasia that involves long tubular bones, especially the tibia and femur. It occurs after puberty and is reported to be more common in women. In this article we describe how Ribbing disease can be differentiated from diseases like Engelmann-Camurati disease, van Buchem disease, Erdheim-Chester disease, osteoid osteoma, chronic osteomyelitis, stress fracture, etc. PMID:20351994

  1. Ribbing disease.

    PubMed

    Mukkada, Philson J; Franklin, Teenu; Rajeswaran, Rangasami; Joseph, Santhosh

    2010-02-01

    Ribbing disease is a rare sclerosing dysplasia that involves long tubular bones, especially the tibia and femur. It occurs after puberty and is reported to be more common in women. In this article we describe how Ribbing disease can be differentiated from diseases like Engelmann-Camurati disease, van Buchem disease, Erdheim-Chester disease, osteoid osteoma, chronic osteomyelitis, stress fracture, etc. PMID:20351994

  2. Evolution of Marek's disease -- a paradigm for incessant race between the pathogen and the host.

    PubMed

    Nair, Venugopal

    2005-09-01

    Marek's disease (MD) is a highly contagious lymphoproliferative disease of poultry caused by the oncogenic herpesvirus designated Marek's disease virus (MDV). MD has a worldwide distribution and is thought to cause an annual loss over 1 bn US dollars to the poultry industry. Originally described as a paralytic disease, today MD is mostly manifested as an acute disease with tumours in multiple visceral organs. MD is controlled essentially by the widespread use of live vaccines administered either in ovo into 18-day-old embryos or into chicks immediately after they hatch. In spite of the success of the vaccines in reducing the losses from the disease in the last 30 years, MDV strains have shown continuous evolution in virulence acquiring the ability to overcome the immune responses induced by the vaccines. During this period, different generations of MD vaccines have been introduced to protect birds from the increasingly virulent MDV strains. However, the virus has countered each new vaccine with ever more virulent strains. This continuous race between the virus and the host is making the control of this poultry health problem a major challenge for the future. PMID:16129338

  3. Paediatric liver transplantation: the surgical view

    PubMed Central

    Vilca-Melendez, H; Heaton, N

    2004-01-01

    Liver transplantation is the accepted treatment for a wide variety of liver diseases in children. Over the past 10 years a number of innovative surgical techniques have been developed to overcome the shortage of size matched donors particularly in children less than 5 years of age. Graft and patient survival at one year after liver transplantation has continued to improve, and is now over 85% and higher for good risk cases. Complications are relatively common, but provided graft function is satisfactory, long term survival for these children is to be expected. The need for retransplantation has fallen significantly. Causes of early mortality include graft dysfunction and sepsis. Late mortality is due to sepsis, post-transplant lymphoproliferative disease, and non-compliance. Long term survival with good graft function and excellent quality of life is possible for the majority of children undergoing liver transplantation. PMID:15466990

  4. General Information about Childhood Non-Hodgkin Lymphoma

    MedlinePLUS

    ... Web site . Lymphoproliferative Disease Associated with a Weakened Immune System Treatment of lymphoproliferative disease in children and adolescents with weakened immune systems may include the following: Surgery with or without ...

  5. Stages of Childhood Non-Hodgkin Lymphoma

    MedlinePLUS

    ... Web site . Lymphoproliferative Disease Associated with a Weakened Immune System Treatment of lymphoproliferative disease in children and adolescents with weakened immune systems may include the following: Surgery with or without ...

  6. Growth hormone interacts with the Marek's disease virus SORF2 protein and is associated with disease resistance in chicken.

    PubMed

    Liu, H C; Kung, H J; Fulton, J E; Morgan, R W; Cheng, H H

    2001-07-31

    Marek's disease (MD) is a lymphoproliferative disease of chickens induced by a herpesvirus, the MD virus (MDV). Because MD is a significant economic problem to the poultry industry, there is great interest in enhancing genetic resistance, which is controlled by multiple genes. The influence of the MHC has been clearly demonstrated, and several relevant quantitative trait loci have been mapped; however, no single gene influencing MD resistance has been identified. Transcription of SORF2 is perturbed in the MDV recombinant clone RM1 due to a solo insertion of the reticuloendotheliosis virus long terminal repeat, which may explain the loss of oncogenicity for this strain. Hypothesizing that SORF2-interacting host proteins are involved in MD resistance, we screened a chicken splenic cDNA library by the yeast two-hybrid assay using SORF2 as bait. The chicken growth hormone (GH) structural peptide was identified, and the specific interaction was verified by coimmunoprecipitation. Immunohistochemical staining and indirect immunofluorescence assay indicated that GH and SORF2 can be coexpressed in MDV-infected cells both in vitro and in vivo. Furthermore, polymorphism in the GH gene (GH1) is associated with the number of tissues with tumors in commercial White Leghorn chickens with the MHC B*2/B*15 genotype. We conclude that GH1 may well be a MD resistance gene. PMID:11470922

  7. European perspective on human polyomavirus infection, replication and disease in solid organ transplantation.

    PubMed

    Hirsch, H H; Babel, N; Comoli, P; Friman, V; Ginevri, F; Jardine, A; Lautenschlager, I; Legendre, C; Midtvedt, K; Muńoz, P; Randhawa, P; Rinaldo, C H; Wieszek, A

    2014-09-01

    Human polyomaviruses (HPyVs) are a growing challenge in immunocompromised patients in view of the increasing number of now 12 HPyV species and their diverse disease potential. Currently, histological evidence of disease is available for BKPyV causing nephropathy and haemorrhagic cystitis, JCPyV causing progressive multifocal leukoencephalopathy and occasionally nephropathy, MCPyV causing Merkel cell carcinoma and TSPyV causing trichodysplasia spinulosa, the last two being proliferative skin diseases. Here, the current role of HPyV in solid organ transplantation (SOT) was reviewed and recommendations regarding screening, monitoring and intervention were made. Pre-transplant screening of SOT donor or recipient for serostatus or active replication is currently not recommended for any HPyV. Post-transplant, however, regular clinical search for skin lesions, including those associated with MCPyV or TSPyV, is recommended in all SOT recipients. Also, regular screening for BKPyV replication (e.g. by plasma viral load) is recommended in kidney transplant recipients. For SOT patients with probable or proven HPyV disease, reducing immunosuppression should be considered to permit regaining of immune control. Antivirals would be desirable for treating proven HPyV disease, but are solely considered as adjunct local treatment of trichodysplasia spinulosa, whereas surgical resection and chemotherapy are key in Merkel cell carcinoma. Overall, the quality of the clinical evidence and the strength of most recommendations are presently limited, but are expected to improve in the coming years. PMID:24476010

  8. Recurrence of secondary glomerular disease after renal transplantation.

    PubMed

    Ponticelli, Claudio; Moroni, Gabriella; Glassock, Richard J

    2011-05-01

    The risk of a posttransplant recurrence of secondary glomerulonephritis (GN) is quite variable. Histologic recurrence is frequent in lupus nephritis, but the lesions are rarely severe and usually do not impair the long-term graft outcome. Patients with Henoch-Schonlein nephritis have graft survival similar to that of other renal diseases, although recurrent Henoch-Schonlein nephritis with extensive crescents has a poor prognosis. Amyloid light-chain amyloidosis recurs frequently in renal allografts but it rarely causes graft failure. Amyloidosis secondary to chronic inflammation may also recur, but this is extremely rare in patients with Behcet's disease or in those with familial Mediterranean fever, when the latter are treated with colchicine. Double organ transplantation (liver/kidney; heart/kidney), chemotherapy, and autologous stem cell transplantation may be considered in particular cases of amyloidosis, such as hereditary amyloidosis or multiple myeloma. There is little experience with renal transplantation in light-chain deposition disease, fibrillary/immunotactoid GN, or mixed cryoglobulinemic nephritis but successful cases have been reported. Diabetic nephropathy often recurs but usually only after many years. Recurrence in patients with small vessel vasculitis is unpredictable but can cause graft failure. However, in spite of recurrence, patient and graft survival rates are similar in patients with small vessel vasculitis compared with those with other renal diseases. Many secondary forms of GN no longer represent a potential contraindication to renal transplantation. The main issues in transplantation of patients with secondary GN are the infectious, cardiovascular, or hepatic complications associated with the original disease or its treatment. PMID:21493742

  9. Farber's Disease

    MedlinePLUS

    ... a group of inherited metabolic disorders called lipid storage diseases, in which excess amounts of lipids (oils, ... Institutes of Health (NIH), conducts research about lipid storage diseases such as Farber’s disease in laboratories at ...

  10. Kidney Disease

    MedlinePLUS

    ... Kidney Disease: What is Kidney Disease? In This Topic What is Kidney Disease? Risk Factors and Prevention ... for More Information National Institute on Aging Related Topics Diabetes High Blood Pressure Heart Failure The information ...

  11. Kennedy's Disease

    MedlinePLUS

    NINDS Kennedy's Disease Information Page Synonym(s): Bulbospinal Muscular Atrophy, X-Linked Spinal and Bulbar Muscular Atrophy Table of Contents ( ... is being done? Clinical Trials Organizations What is Kennedy's Disease? Kennedy's disease is an inherited motor neuron ...

  12. Menkes Disease

    MedlinePLUS

    ... link in the menu on the left. Common Names Kinky hair disease Menkes disease Menkes syndrome Steely hair disease Medical or Scientific Names Congenital hypocupremia (pronounced kuhn-JEN-i-tl hahy- ...

  13. Unicentric mesenteric Castleman’s disease with littoral cell angioma, anemia, growth retardation and amenorrhea: A case report

    PubMed Central

    YANG, LING; ZHAO, SHUANG; LIU, RONG-BO

    2015-01-01

    Castleman’s disease (CD) is a rare lymphoproliferative disorder of unknown origin, and littoral cell angioma (LCA) is a rare vascular tumor of the spleen with an unknown etiology. The current study reports the case of a 28-year-old female who presented with anemia, growth retardation and amenorrhea. Physical examination revealed a mass in the mesentery, splenomegaly with multiple small nodules, hepatomegaly and an infantile uterus. Histopathological analysis of the resected mass and spleen confirmed the diagnosis of hyaline-vascular CD and LCA. The patient’s anemia resolved, and menstruation and breast development also commenced following surgery. To the best of our knowledge, this is the first report of CD accompanied by littoral cell angioma, anemia, growth retardation and amenorrhea. PMID:25789041

  14. Rosai-Dorfman disease of the central nervous system: report of 6 cases and review of the literature.

    PubMed

    Sandoval-Sus, Jose D; Sandoval-Leon, Ana C; Chapman, Jennifer R; Velazquez-Vega, Jose; Borja, Maria J; Rosenberg, Shai; Lossos, Alexander; Lossos, Izidore S

    2014-05-01

    Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is an uncommon benign idiopathic lymphoproliferative disorder. The histologic hallmark of RDD is the finding of emperipolesis displayed by lesional histiocytes. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. As a result, therapeutic approaches to CNS involvement in RDD are not well established. Herein we report 6 cases of RDD with isolated CNS involvement and review the literature on RDD with CNS involvement. One of the presented cases exhibited intramedullary involvement of the spinal cord--a very rare form of RDD with CNS involvement. PMID:24797172

  15. Meningococcal Disease

    MedlinePLUS

    ... of Prestigious 2015 Awards Addressing the Challenges of Serogroup B Meningococcal Disease Outbreaks on Campuses The History of Vaccines: Vaccines for Teenagers 14 Adult Vaccine-Preventable Diseases ...

  16. T CELL BASED THERAPIES FOR MALIGNANCY AND INFECTION IN CHILDHOOD

    PubMed Central

    Ahmed, Nabil; Heslop, Helen E.; Mackall, Crystal L.

    2009-01-01

    One major advance in T cell based immunotherapy in the last twenty years has been the molecular definition of numerous viral and tumor antigens. Adoptive T-cell transfer has shown definite clinical benefit in the prophylaxis and treatment of viral infections that develop in pediatric patients after allogeneic transplant and in Epstein–Barr virus-associated post-transplant lymphoproliferative disease. Developing adoptive T cell therapies for other malignancies presents additional challenges. This article describes the recent advances in T cell based therapies for malignancy and infection in childhood and strategies to enhance the effector functions of T cells and optimize the cellular product, including gene modification and modulation of the host environment. PMID:20307713

  17. Lyme Disease

    MedlinePLUS

    ... of Lyme disease to the Centers for Disease Control and Prevention in 2013. NIAID has a long-standing commitment to conduct Lyme disease research with the major goals of developing better means of diagnosing, treating, and preventing the disease. To ...

  18. Newcastle disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Newcastle disease (ND), referred to as Exotic Newcastle disease (END) in the U. S., is an acute viral disease of domestic poultry and many other bird species and a recognized worldwide problem. Occurrence of END is due to an infection with virulent strains of Newcastle disease virus (NDV) and is a ...

  19. Heart Diseases

    MedlinePLUS

    ... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...

  20. genetic disease

    Microsoft Academic Search

    Gerhard Nahler

    \\u000a Disease linked to a genetic defect such as a mutated gene; there are about 4,000 to 5,000 genetic diseases known to medical\\u000a science such as cystic fibrosis, Down syndrome, sickle cell anemia, haemophilia, Gilles de la Tourette syndrome or Fabry’s\\u000a disease; ? see also gene therapy, orphan diseases.

  1. Crohn's Disease

    MedlinePLUS

    ... Crohn’s disease? Crohn’s disease is a type of inflammatory bowel disease (IBD) that causes inflammation and irritation in the gastrointestinal ( ... before age 20. top of page How is Crohn’s disease evaluated? Your primary doctor will begin by asking ...

  2. Epstein Barr virus-positive mucocutaneous ulcer of the colon associated Hodgkin lymphoma in Crohn's disease.

    PubMed

    Moran, Neil R; Webster, Bradley; Lee, Kenneth M; Trotman, Judith; Kwan, Yiu-Lam; Napoli, John; Leong, Rupert W

    2015-05-21

    Epstein Barr virus (EBV) positive mucocutaneous ulcers (EBVMCU) form part of a spectrum of EBV-associated lymphoproliferative disease. They have been reported in the setting of immunosenescence and iatrogenic immunosuppression, affecting the oropharyngeal mucosa, skin and gastrointestinal tract (GIT). Case reports and series to date suggest a benign natural history responding to conservative management, particularly in the GIT. We report an unusual case of EBVMCU in the colon, arising in the setting of immunosuppression in the treatment of Crohn's disease, with progression to Hodgkin lymphoma 18 mo after cessation of infliximab. The patient presented with multiple areas of segmental colonic ulceration, histologically showing a polymorphous infiltrate with EBV positive Reed-Sternberg-like cells. A diagnosis of EBVMCU was made. The ulcers failed to regress upon cessation of infliximab and methotrexate for 18 mo. Following commencement of prednisolone for her Crohn's disease, the patient developed widespread Hodgkin lymphoma which ultimately presented as a life-threatening lower GIT bleed requiring emergency colectomy. This is the first report of progression of EBVMCU to Hodgkin lymphoma, in the setting of ongoing iatrogenic immunosuppression and inflammatory bowel disease. PMID:26019475

  3. Preoperative embolization for the treatment of cervical Castleman disease.

    PubMed

    Sanchez-Ros-Sanchez, Alberto; Infante-Cossio, Pedro; Gonzalez-Garcia, Alejandro; Borrero-Martin, Juan-Jose

    2012-05-01

    Castleman disease (CD) is a rare benign lymphoproliferative disorder commonly described as a hypervascular mass that causes progressive lymph node enlargement. Head and neck involvement occurs only in 15% to 20% of cases. The recommended treatment in solitary CD is radical resection. Few reports have described the use of angiographic study and preoperative embolization to minimize the intraoperative risk of hemorrhage. We report a clinical case of a solitary large painless, slow-growing mass located in the neck of a 34-year-old woman. Contrast-enhanced computed tomographic and magnetic resonance imaging scan demonstrated a well-defined mass with internal calcifications and peripheral vessels located in the posterior cervical space, extending inferiorly to the supraclavicular space, which moderately enhanced after contrast administration. In the preoperative arteriography, a hypervascularized mass was identified, which mainly received an arterial supply from thyrocervical trunk. Successful embolization with polyvinyl alcohol microparticles was performed, resulting in a significant reduction of intraoperative bleeding, allowing a subsequently safe removal of the tumor. Histopathologic examination corresponded to hyaline vascular-type CD. PMID:22627451

  4. Liver transplantation in alcoholic liver disease current status and controversies

    PubMed Central

    Singal, Ashwani K; Chaha, Khushdeep S; Rasheed, Khalid; Anand, Bhupinderjit S

    2013-01-01

    Alcoholic cirrhosis remains the second most common indication for liver transplantation. A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list. Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients. Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation (recidivism). These patients need to be identified and require alcohol rehabilitation treatment before transplantation. Recidivism to the level of harmful drinking is reported in about 15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants, harmful drinking in the post-transplant period does impact the long-term outcome. The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease. Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome. The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids. Emerging data from retrospective and prospective studies has challenged the 6 mo rule, and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids. PMID:24106395

  5. [Auto-immune diseases and cancers. Second part: auto-immune diseases complicating cancers and their treatment].

    PubMed

    Pasquet, F; Pavic, M; Ninet, J; Hot, A

    2014-10-01

    Autoimmune diseases may reveal or occur during the course of a neoplasia or its treatment. Autoimmune cytopenia, especially haemolytic anaemia, is common in lymphoproliferative disorders such as chronic lymphoid leukemia. The link between cancer and myositis is well established. Dermatomyositis is associated with an increased relative risk of cancer of 3.4 to 4.4. A combination of detection of antibodies against p155 and TEP-computed tomography may be the best approach to ascertain the presence of occult malignancy in patients with dermatomyositis. A cutaneous or a systemic vascularitis may reveal a cancer, most often a haematological malignancy such as hairy cell leukemia. Paraneoplastic polyarthritis have been described in particular with adenocardinoma of the lungs. Underlying neoplasia should be considered in male smokers patients with new onset polyarthritis and poor health status. The prevalence of autoimmune conditions in myelodysplastic syndromes is 10 to 30%. Vasculitis and relapsing polychondritis are the most commonly reported manifestations. Immune manifestations can also be related to treatment. The most common treatment complications are autoimmune haemolytic anaemia with fludarabine and thyroiditis related to interferon and cervical radiotherapy. PMID:25106665

  6. Genetics Home Reference: Autoimmune lymphoproliferative syndrome

    MedlinePLUS

    ... Guillain-Barre syndrome), or the connective tissues (systemic lupus erythematosus) that provide strength and flexibility to structures ... involves lymphoproliferation and the tendency to develop systemic lupus erythematosus. Individuals with this form of the disorder ...

  7. Follicular Lymphoma Presenting with Leptomeningeal Disease

    PubMed Central

    Costa, Ricardo; Costa, Renata

    2014-01-01

    Follicular lymphoma is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Central nervous system metastasis is a very rare complication portending a very poor prognosis. We report a rare case of follicular lymphoma presenting with leptomeningeal involvement achieving a complete remission after initial therapy. PMID:25544910

  8. Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

    ClinicalTrials.gov

    2014-08-13

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Myeloid Leukemia in Remission; Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

  9. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    ClinicalTrials.gov

    2015-03-04

    B-cell Adult Acute Lymphoblastic Leukemia; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma

  10. Wilson disease.

    PubMed

    El-Youssef, Mounif

    2003-09-01

    Wilson disease is a rare disorder of copper metabolism that results in accumulation of copper in the liver and subsequently in other organs, mainly the central nervous system and the kidneys. Advances in the diagnosis and treatment of Wilson disease are discussed, with the emphasis that this is a disease of children, adolescents, and young adults. The myriad manifestations of Wilson disease make its diagnosis dependent on a high index of suspicion, and determination of its genetic background is helping to elucidate the genotype-phenotype correlation and the diversity of presentations. Treatment of Wilson disease has progressed from chelation therapy using D-penicillamine and trientine to the more recent use of zinc and finally to the establishment of liver transplantation as an urgent but excellent modality for fulminant presentation. The evolution of Wilson disease from a uniformly fatal disease to an eminently treatable disease during the past century is an example of the remarkable advances of modern medicine. PMID:12962167

  11. Addison disease

    MedlinePLUS

    Addison disease is a disorder that occurs when the adrenal glands do not produce enough hormones. ... estrogens (female), affect sexual development and sex drive. Addison disease results from damage to the adrenal cortex. ...

  12. Eye Diseases

    MedlinePLUS

    ... the back of the eye Macular degeneration - a disease that destroys sharp, central vision Diabetic eye problems ... defense is to have regular checkups, because eye diseases do not always have symptoms. Early detection and ...

  13. Chagas Disease

    MedlinePLUS

    Chagas disease is caused by a parasite. It is common in Latin America but not in the United States. ... nose, the bite wound or a cut. The disease can also spread through contaminated food, a blood ...

  14. Raynaud's Disease

    MedlinePLUS

    Raynaud's disease is a rare disorder of the blood vessels, usually in the fingers and toes. It causes the ... secondary Raynaud's, which is caused by injuries, other diseases, or certain medicines. People in colder climates are ...

  15. Wilson Disease

    MedlinePLUS

    Wilson disease is a rare inherited disorder that prevents your body from getting rid of extra copper. You need ... copper into bile, a digestive fluid. With Wilson disease, the copper builds up in your liver, and ...

  16. Parasitic Diseases

    MedlinePLUS

    ... a bug bite, or sexual contact. Some parasitic diseases are easily treated and some are not. Parasites ... be seen with the naked eye. Some parasitic diseases occur in the United States. Contaminated water supplies ...

  17. Gaucher's Disease

    MedlinePLUS

    Gaucher's disease is a rare, inherited disorder in which you do not have enough of an enzyme called glucocerebrosidase. ... It usually starts in childhood or adolescence. Gaucher's disease has no cure. Treatment options for types 1 ...

  18. Endocrine Diseases

    MedlinePLUS

    ... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

  19. Addison Disease

    MedlinePLUS

    ... blood pressure and water and salt balance. Addison disease happens if the adrenal glands don't make ... problem with your immune system usually causes Addison disease. The immune system mistakenly attacks your own tissues, ...

  20. Fifth Disease

    MedlinePLUS

    Fifth disease is a viral infection caused by parvovirus B19. The virus only infects humans; it's not the same parvovirus that dogs and cats can get. Fifth disease mostly affects children. Symptoms can include a low ...

  1. Legionnaires' Disease

    MedlinePLUS

    Legionnaires' disease is a type of pneumonia caused by bacteria. You usually get it by breathing in mist from ... spread from person to person. Symptoms of Legionnaires' disease include high fever, chills, a cough, and sometimes ...

  2. Wilson Disease

    MedlinePLUS

    ... Share External Link Disclaimer Digestive Diseases Wilson Disease Alternate Versions PDF Version? (444 KB) You can also ... things psychosis—when a person loses contact with reality Other Signs and Symptoms Other signs and symptoms ...

  3. Grover's Disease

    MedlinePLUS

    ... No, Keep Private Grover's Disease Share | Grover's disease (transient acantholytic dermatosis) is a condition that appears suddenly ... months (which is why it was originally called "transient"). Unfortunately it may last much longer. The cause ...

  4. Autoimmune Diseases

    MedlinePLUS

    ... disease fact sheet Inflammatory bowel disease fact sheet Lupus fact sheet Myasthenia gravis fact sheet Stress and ... Office on Women's Health, the Could I Have Lupus? Campaign is raising awareness about lupus and providing ...

  5. Whipple's disease

    MedlinePLUS

    Maiwald M, von Herbay A, Relman DA. Whipple's disease. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease . 9th ed. Philadelphia, PA: Saunders ...

  6. Fifth disease

    MedlinePLUS

    Parvovirus B19; Erythema infectiosum; Slapped cheek rash ... Fifth disease is caused by human parvovirus B19. It often affects preschoolers or school-age children during the spring. The disease spreads through the fluids in the nose and ...

  7. Fungal Diseases

    MedlinePLUS

    ... Search The CDC Cancel Submit Search The CDC Fungal Diseases Note: Javascript is disabled or is not supported ... CDC.gov . Recommend on Facebook Tweet Share Compartir Fungal diseases can affect anyone. Learning about them can help ...

  8. Wildlife Diseases 

    E-print Network

    Texas Wildlife Services

    2007-03-13

    Some wildlife diseases can be transmitted to humans. This leaflet explains the causes and symptoms of rabies, giardiasis, bubonic plague, Rocky Mountain spotted fever, Lyme disease, tularemia, leptospirosis and histoplasmosis....

  9. Heart Disease

    MedlinePLUS

    ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

  10. Glanzmann's disease

    MedlinePLUS

    Glanzmann's disease is a rare disorder of blood platelets , which results in easy bruising and nosebleeds . ... Glanzmann's disease is caused by the lack of a protein that is normally on the surface of ...

  11. Graves' Disease

    MedlinePLUS

    ... is called Graves’ ophthalmopathy (GO). [ Top ] What is Graves’ ophthalmopathy? Graves’ ophthalmopathy is a condition associated with Graves’ disease that ... may also have bulging eyes, a condition called Graves’ ophthalmopathy (GO). Graves’ disease is most often treated with ...

  12. Hookworm Disease

    MedlinePLUS

    ... Tools Print this page Get email updates Order publications Volunteer for Clinical Studies Help people who are suffering from hookworm by volunteering for NIAID clinical studies on ClinicalTrials.gov . Related Links Parasitic Roundworm Diseases Laboratory of Parasitic Diseases ...

  13. Behçet's disease

    Microsoft Academic Search

    Heidi C. Mangelsdorf; Wain L. White; Joseph L. Jorizzo

    1996-01-01

    Background: Behçet's disease is a multisystem disease that is rare in the United States.Objective: The purpose of our study was to assess the characteristics and treatment of a series of patients with Behçet's disease in the United States.Methods: A retrospective clinical review of 25 patients with Behçet's disease was performed, and histopathologic findings and therapeutic modalities were reviewed.Results: All patients

  14. Rice Diseases

    E-print Network

    Jones, Roger K.

    1987-01-01

    (Blank P~ge in O .... a1-BUUetinl ? ~" -: . . r ". ./ RICE DISEASES Roger K. Jones * Rice diseases reduce yields in Texas by an average of 12 percent each year. The yield loss in certain fields with a history of disease may exceed 30... percent in some seasons. Disease development in individual fields depends upon the interaction of several factors including the genetic resistance of the variety planted, cropping practices, environmental conditions (such as temperature, dew periods...

  15. Kawasaki disease

    PubMed Central

    Kawasaki, Tomisaku

    2006-01-01

    Short history of Kawasaki disease, clinical features (principal symptoms and other significant symptoms or findings), diagnosis, cardiovascular involvement, epidemiology. Pathological features (lesion of vessels and lesion of organs exclusive of vessels), comparison between infantile periarteritis nodosa (IPN)/Kawasaki disease and classic periarteritis nodosa (CPN), etiology, treatment and management of Kawasaki disease are described. PMID:25792773

  16. NEWCASTLE DISEASE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Concise information about Newcastle disease (ND) is provided for a book that serves as a quick reference guide to the infectious, parasitic, metabolic, nutritional, and toxic diseases of domesticated animals and birds as well some exotic species that a veterinarian might encounter. Newcastle disease...

  17. Fifth Disease

    MedlinePLUS

    ... are immune. How is fifth disease spread? Fifth disease is spread by coming into contact with saliva or mucus carrying the virus. For example, it can be spread by coughing, sneezing or sharing items. Frequent hand washing may ... Don’t worry! Fifth disease is caused by parvovirus, but it isn’t ...

  18. Kawasaki disease.

    PubMed

    Sundel, Robert P

    2015-01-01

    Kawasaki disease (KD) is the archetypal pediatric vasculitis, exemplifying the unique aspects and challenges of vascular inflammation in children. The condition is almost unheard of in adults, is closely associated with infections, and is self-limited, with fever resolving after an average of 12 days even without treatment. Yet KD is also a potentially fatal disease and the most common cause of acquired heart disease in the developed world. Unraveling of the developmental, immunologic, and genetic secrets of Kawasaki disease promises to improve our understanding of vasculitis in particular, and perhaps also to provide a window on the fundamental mysteries of inflammatory diseases in general. PMID:25399940

  19. Epstein Barr virus-positive mucocutaneous ulcer of the colon associated Hodgkin lymphoma in Crohn’s disease

    PubMed Central

    Moran, Neil R; Webster, Bradley; Lee, Kenneth M; Trotman, Judith; Kwan, Yiu-Lam; Napoli, John; Leong, Rupert W

    2015-01-01

    Epstein Barr virus (EBV) positive mucocutaneous ulcers (EBVMCU) form part of a spectrum of EBV-associated lymphoproliferative disease. They have been reported in the setting of immunosenescence and iatrogenic immunosuppression, affecting the oropharyngeal mucosa, skin and gastrointestinal tract (GIT). Case reports and series to date suggest a benign natural history responding to conservative management, particularly in the GIT. We report an unusual case of EBVMCU in the colon, arising in the setting of immunosuppression in the treatment of Crohn’s disease, with progression to Hodgkin lymphoma 18 mo after cessation of infliximab. The patient presented with multiple areas of segmental colonic ulceration, histologically showing a polymorphous infiltrate with EBV positive Reed-Sternberg-like cells. A diagnosis of EBVMCU was made. The ulcers failed to regress upon cessation of infliximab and methotrexate for 18 mo. Following commencement of prednisolone for her Crohn’s disease, the patient developed widespread Hodgkin lymphoma which ultimately presented as a life-threatening lower GIT bleed requiring emergency colectomy. This is the first report of progression of EBVMCU to Hodgkin lymphoma, in the setting of ongoing iatrogenic immunosuppression and inflammatory bowel disease. PMID:26019475

  20. Skin Diseases

    Microsoft Academic Search

    Roderick Hay; Sandra E. Bendeck; Suephy Chen; Roberto Estrada; Anne Haddix; Tonya McLeod; Antoine Mahé

    In assigning health priorities, skin diseases are sometimes thought of, in planning terms, as small-time players in the global league of illness compared with diseases that cause signif- icant mortality, such as HIV\\/AIDS, community-acquired pneu- monias, and tuberculosis. However, skin problems are generally among the most common diseases seen in primary care settings in tropical areas, and in some regions

  1. Gaucher Disease

    PubMed Central

    Nagral, Aabha

    2014-01-01

    Gaucher disease is the commonest lysosomal storage disease seen in India and worldwide. It should be considered in any child or adult with an unexplained splenohepatomegaly and cytopenia which are seen in the three types of Gaucher disease. Type 1 is the non-neuronopathic form and type 2 and 3 are the neuronopathic forms. Type 2 is a more severe neuronopathic form leading to mortality by 2 years of age. Definitive diagnosis is made by a blood test–the glucocerebrosidase assay. There is no role for histological examination of the bone marrow, liver or spleen for diagnosis of the disease. Molecular studies for mutations are useful for confirming diagnosis, screening family members and prognosticating the disease. A splenectomy should not be performed except for palliation or when there is no response to enzyme replacement treatment or no possibility of getting any definitive treatment. Splenectomy may worsen skeletal and lung manifestations in Gaucher disease. Enzyme replacement therapy (ERT) has completely revolutionized the prognosis and is now the standard of care for patients with this disease. Best results are seen in type 1 disease with good resolution of splenohepatomegaly, cytopenia and bone symptoms. Neurological symptoms in type 3 disease need supportive care. ERT is of no benefit in type 2 disease. Monitoring of patients on ERT involves evaluation of growth, blood counts, liver and spleen size and biomarkers such as chitotriosidase which reflect the disease burden. Therapy with ERT is very expensive and though patients in India have so far got the drug through a charitable access programme, there is a need for the government to facilitate access to treatment for this potentially curable disease. Bone marrow transplantation is an inferior option but may be considered when access to expensive ERT is not possible. PMID:25755533

  2. Lyme Disease

    NSDL National Science Digital Library

    Dr. Leslie Nader (MSMR)

    1992-04-14

    A little microorganism called a spirochete causes Lyme disease, which can cause extremely severe symptoms, including neck stiffness, acute headaches, neurological damage, and rheumatoid arthritis-like problems. Lyme disease is transmitted by ticks and so is tied to the ticks' life cycle. Lyme disease is also seen by veterinarians, largely in dogs, for whom it can be fatal. Lyme research is ongoing on numerous fronts.

  3. Disease Detective

    NSDL National Science Digital Library

    2014-01-28

    This activity (on pages 35-43) lets learners analyze a "herd of elk" to detect the spread of a bacterial disease called brucellosis. The activity simulates how wildilfe veterinarians study elk in the wild by sampling only a subset of the animals. Based on a brucellosis problem with elk in Yellowstone National Park, learners cut out representations for two herds and then pick some at random to "test" for disease (denoted as a plus sign on a diseased animal). The results indicate that elk fed in Wyoming over the winter have more disease than the wild elk that go north to Montana

  4. Moyamoya disease.

    PubMed Central

    Farrugia, M.; Howlett, D. C.; Saks, A. M.

    1997-01-01

    Moyamoya disease is a rare cerebrovascular condition of uncertain aetiology commonly affecting young persons. The disease is mainly seen in Japanese patients. We report two cases of moyamoya disease in Caucasian women and review the postulated aetiological factors and associated conditions as well as the spectrum of invasive and non-invasive imaging modalities useful in the diagnosis and follow-up of the disease, with particular reference to the developing role of magnetic resonance imaging and angiography. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9373593

  5. Huntington's Disease

    PubMed Central

    Finkbeiner, Steven

    2011-01-01

    Huntington's disease (HD) is the most common inherited neurodegenerative disease and is characterized by uncontrolled excessive motor movements and cognitive and emotional deficits. The mutation responsible for HD leads to an abnormally long polyglutamine (polyQ) expansion in the huntingtin (Htt) protein, which confers one or more toxic functions to mutant Htt leading to neurodegeneration. The polyQ expansion makes Htt prone to aggregate and accumulate, and manipulations that mitigate protein misfolding or facilitate the clearance of misfolded proteins tend to slow disease progression in HD models. This article will focus on HD and the evidence that it is a conformational disease. PMID:21441583

  6. [Cardiological diseases].

    PubMed

    Gross, L; Massberg, S; Sibbing, D

    2013-10-01

    Knowledge of rare but important clinical disease symptoms in cardiology is of vital importance in the daily routine as severe courses of disease as well as death may be prevented by early diagnosis, effective monitoring and timely initiation of an adequate therapy. In this article an important rhythmological disease, arrhythmogenic right ventricular cardiomyopathy, as well as two significant structural diseases, takotsubo (stress-related) cardiomyopathy and aortic aneurysm related to Marfan syndrome, as well as their implications for clinical practice will be presented. PMID:24005787

  7. Lyme Disease

    MedlinePLUS

    ... information on enabling JavaScript. Lyme Disease Skip Content Marketing ... mysterious group of rheumatoid arthritis cases occurred among children in Lyme, Connecticut, and two neighboring towns. Puzzled, ...

  8. Expression of a virus-derived cytokine, KSHV vIL-6, in HIV-seronegative Castleman's disease.

    PubMed Central

    Parravinci, C.; Corbellino, M.; Paulli, M.; Magrini, U.; Lazzarino, M.; Moore, P. S.; Chang, Y.

    1997-01-01

    Castleman's disease is a rare B cell lymphoproliferative disorder related to excess interleukin-6 (IL-6)-like activity. Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8), which encodes a functional cytokine (vIL-6), has been found in some patients with Castleman's disease. Lymph nodes from 14 HIV-seronegative Castleman's disease patients were compared to hyperplastic lymph nodes from 25 HIV-seronegative patients as well as Kaposi's sarcoma lesions from 48 patients for KSHV infection and vIL-6, human IL-6, and Epstein-Barr virus EBER expression. While all Kaposi's sarcoma tissues examined were polymerase chain reaction-positive and all control lymph nodes were polymerase chain reaction-negative for KSHV, none had detectable vIL-6 expression. Six of 14 (43%) Castleman's tissues were positive for KSHV by polymerase chain reaction and all 6 had evidence of vIL-6 expression by immunohistochemistry. vIL-6-positive Castleman's disease patients generally had the multicentric plasma cell variant form of the disease and had a rapidly fatal clinical course frequently associated with autoimmune hemolytic anemia and gammopathy. In contrast, 7 (88%) of the 8 vIL-6-negative Castleman's disease patients had localized disease and have remained disease-free after therapy. KSHV vIL-6 expression appears to be limited to hematopoietic cells and is not present in Kaposi's sarcoma spindle cells. These data suggest that Castleman's disease is a syndrome of multiple etiologies involving aberrant IL-6 activity from either endogenous or viral sources. Images Figure 1. A Figure 2. A PMID:9403701

  9. Management of hepatitis C in patients with chronic kidney disease

    PubMed Central

    Carvalho-Filho, Roberto J; Feldner, Ana Cristina CA; Silva, Antonio Eduardo B; Ferraz, Maria Lucia G

    2015-01-01

    Hepatitis C virus (HCV) infection is highly prevalent among chronic kidney disease (CKD) subjects under hemodialysis and in kidney transplantation (KT) recipients, being an important cause of morbidity and mortality in these patients. The vast majority of HCV chronic infections in the hemodialysis setting are currently attributable to nosocomial transmission. Acute and chronic hepatitis C exhibits distinct clinical and laboratorial features, which can impact on management and treatment decisions. In hemodialysis subjects, acute infections are usually asymptomatic and anicteric; since spontaneous viral clearance is very uncommon in this context, acute infections should be treated as soon as possible. In KT recipients, the occurrence of acute hepatitis C can have a more severe course, with a rapid progression of liver fibrosis. In these patients, it is recommended to use pegylated interferon (PEG-IFN) in combination with ribavirin, with doses adjusted according to estimated glomerular filtration rate. There is no evidence suggesting that chronic hepatitis C exhibits a more aggressive course in CKD subjects under conservative management. In these subjects, indication of treatment with PEG-IFN plus ribavirin relies on the CKD stage, rate of progression of renal dysfunction and the possibility of a preemptive transplant. HCV infection has been associated with both liver disease-related deaths and cardiovascular mortality in hemodialysis patients. Among those individuals, low HCV viral loads and the phenomenon of intermittent HCV viremia are often observed, and sequential HCV RNA monitoring is needed. Despite the poor tolerability and suboptimal efficacy of antiviral therapy in CKD patients, many patients can achieve sustained virological response, which improve patient and graft outcomes. Hepatitis C eradication before KT theoretically improves survival and reduces the occurrence of chronic graft nephropathy, de novo glomerulonephritis and post-transplant diabetes mellitus. PMID:25593456

  10. Meniere's disease

    Microsoft Academic Search

    A. L. James; M. A. Thorp

    2007-01-01

    INTRODUCTION: Meniere's disease causes recurrent vertigo, hearing loss, tinnitus, and fullness or pressure in the ear, which mainly affects adults aged 40-60 years. Meniere's disease is at first progressive but fluctuating, and episodes can occur in clusters. Vertigo usually resolves but hearing deteriorates, and symptoms other than hearing loss and tinnitus usually improve regardless of treatment. METHODS AND OUTCOMES: We

  11. Renovascular disease

    Microsoft Academic Search

    Philip A. Kalra

    2011-01-01

    In Western populations, fibromuscular disease (FMD) accounts for around 10% of all cases of renal artery stenosis (RAS), usually presenting as hypertension in young patients, most often women, and there is often a successful response after angioplasty. Atherosclerotic renovascular disease (ARVD) is very common, and accounts for the remaining 90% of cases of RAS. ARVD is frequently associated with hypertension

  12. Pericardial Diseases

    Microsoft Academic Search

    Cécile Tissot; Christina M. Phelps; Eduardo M. da Cruz; Shelley D. Miyamoto

    \\u000a Pericardial diseases are defined as structural or functional abnormalities of the visceral or parietal pericardium that may\\u000a or may not have an impact on cardiac function. Diseases of the pericardium include a spectrum of acquired and congenital problems\\u000a consisting of infectious and inflammatory processes, neoplastic lesions, as well as congenital structural defects.

  13. Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases

    PubMed Central

    BONA, G; DEFRANCO, S; CHIOCCHETTI, A; INDELICATO, M; BIAVA, A; DIFRANCO, D; DIANZANI, I; RAMENGHI, U; CORRIAS, A; WEBER, G; DE SANCTIS, V; IUGHETTI, L; RADETTI, G; DIANZANI, U

    2003-01-01

    Triggering of the Fas receptor induces T cell apoptosis and is involved in shutting-off the immune response. Inherited defects impairing Fas function cause the autoimmune lymphoproliferative syndrome, and may play a role in other autoimmune diseases. The aim of this work was to analyse the Fas function in paediatric patients with thyroid autoimmunities. We found that T cells from 24/28 patients with Graves’ disease (GD) and 12/35 patients with Hashimoto's thyroiditis (HT) displayed defective Fas function. In HT, the defect was more frequent in patients requiring replacement therapy (11/20) than in those not requiring (1/15); moreover, in untreated HT the highest defect was displayed by patients with the highest levels of autoantibodies. Fas was always expressed at normal levels and no Fas mutations were detected. Analysis of the healthy parents of seven Fas-resistant patients showed that several of them were Fas-resistant, which suggests a genetic component. Fusion of Fas-resistant T cells with the Fas-sensitive HUT78 T cell line generated Fas-resistant hybrid cells, which suggests the presence of molecules exerting a dominant negative effect on Fas function. Analysis of Fas-induced activation of caspase-8 and -9 showed decreased activity of both caspases in HT, whereas activity of caspase-9 was increased and that of caspase-8 was decreased in GD. These data suggest that heterogeneous inherited defects impairing Fas function favour the development of thyroid autoimmunities. PMID:12930371

  14. Wilson's disease.

    PubMed

    Ala, Aftab; Walker, Ann P; Ashkan, Keyoumars; Dooley, James S; Schilsky, Michael L

    2007-02-01

    Progressive hepatolenticular degeneration, or Wilson's disease, is a genetic disorder of copper metabolism. Knowledge of the clinical presentations and treatment of the disease are important both to the generalist and to specialists in gastroenterology and hepatology, neurology, psychiatry, and paediatrics. Wilson's disease invariably results in severe disability and death if untreated. The diagnosis is easily overlooked but if discovered early, effective treatments are available that will prevent or reverse many manifestations of this disorder. Studies have identified the role of copper in disease pathogenesis and clinical, biochemical, and genetic markers that can be useful in diagnosis. There are several chelating agents and zinc salts for medical therapy. Liver transplantation corrects the underlying pathophysiology and can be lifesaving. The discovery of the Wilson's disease gene has opened up a new molecular diagnostic approach, and could form the basis of future gene therapy. PMID:17276780

  15. Mitochondrial diseases.

    PubMed

    Lee, Young-Mock

    2012-03-01

    Mitochondria contain the respiratory chain enzyme complexes that carry out oxidative phosphorylation and produce the main part of cellular energy in the form of ATP. Although several proteins related with signalling, assembling, transporting, and enzymatic function can be impaired in mitochondrial diseases, most frequently the activity of the respiratory chain protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. Mitochondrial diseases usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Neuromuscular system is frequently affected in mitochondrial diseases. Although there is actually no specific therapy and cure for mitochondrial diseases, the understanding of the pathophysiology may further facilitate the diagnostic approach and open perspectives to future in mitochondrial diseases. PMID:24649452

  16. Kidney transplantation for systemic sclerosis improves survival and may modulate disease activity.

    PubMed

    Gibney, Eric M; Parikh, Chirag R; Jani, Alkesh; Fischer, Michael J; Collier, David; Wiseman, Alexander C

    2004-12-01

    Systemic sclerosis (SS) may lead to sclerodema renal crisis, an unusual cause of end-stage renal disease (ESRD) with historically poor hemodialysis outcomes. Little information is available on outcomes after kidney transplantation. Information from the UNOS registry was obtained on SS patients in the United States, listed for kidney transplants between 1985-2002. We compared survival at 1 and 3 years in patients who received cadaveric transplants with patients who remained on the waiting list. Graft survival, cause of graft loss, frequency of early graft loss and pre- and post-transplant skin scores were analyzed. Two hundred and fifty-eight patients with SS were listed for transplantation. Survival was significantly prolonged in patients receiving transplants (p = 0.005). Graft survival at 1 and 3 years was 68% and 60%. Early graft loss was common. Skin scores improved in all four subjects at our center, with an average decline of 60.7% (p = 0.024). Kidney transplantation confers a survival benefit in ESRD due to SS. Transplantation may be associated with an improvement in systemic manifestations of disease. Despite suboptimal graft survival, kidney transplant should be considered the treatment of choice in ESRD due to SS. PMID:15575905

  17. MELDEQ : An alternative Model for End-Stage Liver Disease score for patients with hepatocellular carcinoma.

    PubMed

    Marvin, Michael R; Ferguson, Nicole; Cannon, Robert M; Jones, Christopher M; Brock, Guy N

    2015-05-01

    Multiple studies have demonstrated an advantage for hepatocellular carcinoma (HCC) patients under the current liver allocation system, such that the United Network for Organ Sharing (UNOS) recently voted in support of a proposal to delay granting Model for End-Stage Liver Disease (MELD) exception points to all HCC patients for 6 months, independently of a candidate's native MELD score or alpha-fetoprotein (AFP) level. We obtained UNOS data on adult patients who were added to the wait list between January 22, 2005 and September 30, 2009, and we explored the relationship between HCC, MELD, AFP, and other factors that contribute to not only dropout on the wait list but posttransplant survival as well. The aim was to establish an equivalent Model for End-Stage Liver Disease (MELDEQ ) score for HCC patients that would reduce the disparity in access to transplantation between HCC and non-HCC patients. We determined risk groups for HCC patients with dropout hazards equivalent to those of non-HCC patients, and we evaluated projections for HCC wait-list dropout/transplantation probabilities on the basis of the MELDEQ prioritization scheme. Projections indicate that lower risk HCC patients (MELDEQ ???18) would have dropout probabilities similar to those of non-HCC patients in the same MELD score range, whereas dropout probabilities for higher risk HCC patients would actually be improved. The posttransplant survival of all HCC risk groups is lower than that of their non-HCC counterparts, with 1-year survival of 0.77 (95% CI, 0.70-0.85) for MELDEQ scores???31. These results suggest that HCC patients with a combination of a low biochemical MELD score and a low AFP level (MELDEQ ???15) would receive a marked advantage in comparison with patients with chemical MELD scores in a similar range and that a delay of 6 months for listing may be appropriate. In contrast, patients with MELDEQ scores?>?15 would likely be adversely affected by a universal 6-month delay in listing. Liver Transpl 21:612-622, 2015. © 2015 AASLD. PMID:25694099

  18. Three-yr safety and efficacy of everolimus and low-dose cyclosporine in de novo pediatric kidney transplant patients.

    PubMed

    Ferraresso, Mariano; Belingheri, Mirco; Ginevri, Fabrizio; Murer, Luisa; Dello Strologo, Luca; Cardillo, Massimo; Parodi, Angelica; Ghirardo, Giulia; Guzzo, Isabella; Innocente, Annalisa; Ghio, Luciana

    2014-06-01

    The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty-seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.5-3 ?g/mL), and prednisone. Three wk later everolimus was started (C0:5-10 ng/mL), CyA was reduced (C2:600 ng/mL after 90 days 300 ng/mL), and MMF discontinued. During the three-yr period patient and graft survivals were 96%. One patient died for causes unrelated to the immunosuppression. Cumulative acute rejection rate including protocol and indication biopsies was 21.9%. None of the patients had signs of chronic humoral rejection. Incidence of dnDSA was 5%, 11%, and 22% at one, two, and three yr post-transplant, respectively. Mean glomerular filtration rate measured at one yr and three yr post-transplant was 105.5 ± 31 and 110.7 ± 27 mL/min/1.73 m(2), respectively. A growth velocity of 7.7 ± 6.7 cm/yr was achieved with positive catch-up growth. No malignancy or post-transplant lymphoproliferative diseases were diagnosed. In conclusion, the treatment based on basiliximab induction, everolimus, low-dose cyclosporine, and low-dose prednisone leads to good long-term efficacy in de novo pediatric KT recipients. PMID:24802342

  19. Prolonged sirolimus administration after allogeneic hematopoietic cell transplantation is associated with decreased risk for moderate-severe chronic graft-versus-host disease

    PubMed Central

    Pidala, Joseph; Kim, Jongphil; Alsina, Melissa; Ayala, Ernesto; Betts, Brian C.; Fernandez, Hugo F.; Field, Teresa; Jim, Heather; Kharfan-Dabaja, Mohamed A.; Locke, Frederick L.; Mishra, Asmita; Nishihori, Taiga; Ochoa-Bayona, Leonel; Perez, Lia; Riches, Marcie; Anasetti, Claudio

    2015-01-01

    Effective pharmacological strategies employed in allogeneic hematopoietic cell transplantation should prevent serious chronic graft-versus-host disease and facilitate donor-recipient immune tolerance. Based on demonstrated pro-tolerogenic activity, sirolimus (rapamycin) is an agent with promise to achieve these goals. In a long-term follow-up analysis of a randomized phase II trial comparing sirolimus/tacrolimus versus methotrexate/tacrolimus for graft-versus-host disease prevention in matched sibling or unrelated donor transplant, we examined the impact of prolonged sirolimus administration (? 1 year post-transplant). Median follow-up time for surviving patients at time of this analysis was 41 months (range 27–60) for sirolimus/tacrolimus and 49 months (range 29–63) for methotrexate/tacrolimus. Sirolimus/tacrolimus patients had significantly lower National Institutes of Health Consensus moderate-severe chronic graft-versus-host disease (34% vs. 65%; P=0.004) and late acute graft-versus-host disease (20% vs. 43%; P=0.04). While sirolimus/tacrolimus patients had lower prednisone exposure and earlier discontinuation of tacrolimus (median time to tacrolimus discontinuation 368 days vs. 821 days; P=0.002), there was no significant difference in complete immune suppression discontinuation (60-month estimate: 43% vs. 31%; P=0.78). Prolonged sirolimus administration represents a viable approach to mitigate risk for moderate-severe chronic and late acute graft-versus-host disease. Further study of determinants of successful immune suppression discontinuation is needed. PMID:25840599

  20. Infectious bursal disease (Gumboro disease).

    PubMed

    van den Berg, T P; Eterradossi, N; Toquin, D; Meulemans, G

    2000-08-01

    Infectious bursal disease (IBD) (Gumboro disease) has been described throughout the world, and the socio-economic significance of the disease is considerable world-wide. Various forms of the disease have been described, but typing remains unclear, since antigenic and pathotypic criteria are used indiscriminately, and the true incidence of different types is difficult to determine. Moreover, the infection, when not fatal, leads to a degree of immunosuppression which is often difficult to measure. Finally, the control measures used are subject to variations, and seldom follow a specific or standardised plan. In the context of expanding international trade, the authors provide an overview of existing knowledge on the subject to enhance available information on the epidemiology of IBD, the identification of reliable viral markers for diagnosis, and the implementation of specific control measures to ensure a global and co-ordinated approach to the disease. PMID:10935278

  1. Dercum's disease.

    PubMed

    Wortham, Noel C; Tomlinson, Ian Pm

    2005-01-01

    Dercum's disease (adiposis dolorosa, lipomatosis dolorosa morbus Dercum), is a rare disorder resulting in painful fatty deposits around the upper legs, trunk, and upper arms. The portrait painted of Dercum's disease is very complicated, with many other disorders seen associated with the disease. There are no clear pathological mechanisms known, although it is suspected that there is either a metabolic or autoimmune component involved. Here, the authors review the literature to date, including some information from their own studies. In particular, the authors will look at the different strands of evidence pointing to the pathological mechanism of the disorder. PMID:15891252

  2. Celiac disease

    Microsoft Academic Search

    Ahmad S. Abdulkarim; Joseph A. Murray

    2002-01-01

    Opinion statement  \\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Individuals with celiac disease present with a wide array of symptoms and signs. Celiac disease can result in substantial\\u000a injury to the small intestine, deleterious effects on other organ systems, and an overall doubling of mortality. The role\\u000a of the gastroenterologist is primarily to make the diagnosis and then to ensure that patients with celiac disease receive

  3. Analyses of the spleen proteome of chickens infected with Marek's disease virus

    SciTech Connect

    Thanthrige-Don, Niroshan; Abdul-Careem, Mohamed F. [Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada); Shack, L. Allen; Burgess, Shane C. [Department of Basic Sciences, Mississippi State University (United States); Sharif, Shayan, E-mail: shayan@uoguelph.c [Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada)

    2009-08-01

    Marek's disease virus (MDV), which causes a lymphoproliferative disease in chickens, is known to induce host responses leading to protection against disease in a manner dependent on genetic background of chickens and virulence of the virus. In the present study, changes in the spleen proteome at 7, 14 and 21 days post-infection in response to MDV infection were studied using two-dimensional polyacrylamide gel electrophoresis. Differentially expressed proteins were identified using one-dimensional liquid chromatography electrospray ionization tandem mass spectrometry (1D LC ESI MS/MS). Comparative analysis of multiple gels revealed that the majority of changes had occurred at early stages of the disease. In total, 61 protein spots representing 48 host proteins were detected as either quantitatively (false discovery rate (FDR) <= 0.05 and fold change >= 2) or qualitatively differentially expressed at least once during different sampling points. Overall, the proteins identified in the present study are involved in a variety of cellular processes such as the antigen processing and presentation, ubiquitin-proteasome protein degradation (UPP), formation of the cytoskeleton, cellular metabolism, signal transduction and regulation of translation. Notably, early stages of the disease were characterized by changes in the UPP, and antigen presentation. Furthermore, changes indicative of active cell proliferation as well as apoptosis together with significant changes in cytoskeletal components that were observed throughout the experimental period suggested the complexity of the pathogenesis. The present findings provide a basis for further studies aimed at elucidation of the role of these proteins in MDV interactions with its host.

  4. Learning about Dercum Disease

    MedlinePLUS

    ... genetic terms used on this page. Learning About Dercum Disease What is Dercum disease? What are the ... Disease Additional Resources for Dercum Disease What is Dercum disease? Dercum disease - also known as Adiposis Dolorosa, ...

  5. Wilson Disease

    MedlinePLUS

    ... in copper, such as shellfish liver mushrooms nuts chocolate People should not eat these foods during the ... in copper, such as shellfish liver mushrooms nuts chocolate A person cannot prevent Wilson disease; however, people ...

  6. Addison's Disease

    MedlinePLUS

    ... do not produce enough corticosteroid hormones, such as cortisol and aldosterone. Addison’s disease is most common among ... making. If your body is not making enough cortisol, your doctor may prescribe hydrocortisone, prednisone, or cortisone ...

  7. Digestive diseases

    MedlinePLUS

    Digestive diseases are disorders of the digestive tract, which is sometimes called the gastrointestinal (GI) tract. In digestion, food and drink are broken down into small parts (called nutrients) ...

  8. Batten Disease

    MedlinePLUS

    ... NCL, the neurologist needs the individual's medical and family history and information from various laboratory tests. Diagnostic tests used for NCLs include: blood or urine tests . These tests can detect abnormalities that may indicate Batten disease. For example, elevated ...

  9. Huntington's Disease

    MedlinePLUS

    ... gene with an eye toward understanding how it causes disease in the human body. What research is being done? Scientific investigations using electronic and other technologies enable scientists to see what the defective gene ...

  10. Peyronie's Disease

    MedlinePLUS

    ... The knowledge gained from these studies is advancing scientific understanding of why kidney diseases and urinary tract disorders develop and is leading to improved methods of diagnosing, treating, and preventing them. Clinical trials ...

  11. Lung disease

    MedlinePLUS

    ... the lungs to take in oxygen and release carbon dioxide. People with this type of lung disorder often ... the lungs to take up oxygen and release carbon dioxide. These diseases may also affect heart function. An ...

  12. Graves disease

    MedlinePLUS

    ... is called hyperthyroidism. (An underactive thyroid leads to hypothyroidism .) Graves disease is the most common cause of ... radioactive iodine usually will cause an underactive thyroid (hypothyroidism). Without getting the correct dosage of thyroid hormone ...

  13. Celiac Disease

    Microsoft Academic Search

    Peter H. R. Green; Christophe Cellier

    2007-01-01

    Celiac disease is induced by the ingestion of gluten, which is derived from wheat, barley, and rye. The gluten protein is enriched in glutamine and proline and is poor- ly digested in the human upper gastrointestinal tract. The term \\

  14. Parkinson's Disease

    MedlinePLUS

    ... is responsible for the core features, other affected locations contribute to the complicated picture of Parkinson's. Parkinson's disease is both chronic, meaning it lasts for a long time, and progressive, ...

  15. Alexander Disease

    MedlinePLUS

    ... that accumulate in non-neuronal cells of the brain called astrocytes. Rosenthal fibers are sometimes found in other disorders, but not in the same amount or area of the brain that are featured in Alexander disease. The infantile ...

  16. Glomerular Diseases

    MedlinePLUS

    ... that affects the entire body, like diabetes or lupus. Many different kinds of diseases can cause swelling ... may affect only specific organs or regions. Systemic lupus erythematosus (SLE) affects many parts of the body: ...

  17. Nail Diseases

    MedlinePLUS

    ... smooth and consistent in color. Specific types of nail discoloration and changes in growth rate can be signs of lung, heart, kidney, and liver diseases, as well as diabetes and anemia. White spots ...

  18. Planning Diseases.

    ERIC Educational Resources Information Center

    Gabel, Medard

    1984-01-01

    To solve societal problems, both local and global, a global approach is needed. Serious diseases that are crippling present-day problem solving and planning are discussed, and the characteristics of a healthy, effective planning approach are described. (RM)

  19. Leishmaniasis Disease

    MedlinePLUS

    ... message, please visit this page: About CDC.gov . Parasites - Leishmaniasis Parasites Home Share Compartir Disease Ulcerative skin lesion, with ... with some of the species (types) of the parasite that cause cutaneous leishmaniasis in parts of Latin ...

  20. Canavan Disease

    MedlinePLUS

    ... brain responsible for making myelin sheaths, known as oligodendrocytes, cannot properly complete this critical developmental task. Myelin ... support for nerve cells. In Canavan disease, many oligodendrocytes do not mature and instead die, leaving nerve ...

  1. Ormond's disease.

    PubMed

    Kovács, T; Besznyák, I; Köves, I; Petri, K

    Three cases of Ormond's disease (syndrome) are described, and the aetiopathogenesis, clinical picture and diagnostics of the disease are dealt with in this report. Besides, the traditional therapy and the new therapeutic possibilities are discussed. For a disease of low incidence and assumed autoimmune origin malignancy cannot be excluded. Therefore, surgical exploration and histological verification are indispensable interventions in every case of Ormond's disease. In two of the present cases, steroid was administered in defence of percutaneous nephrostomy. In two cases, the recently recommended anti-oestrogen therapy was successful. Stagnation, or even regression, of the process followed. The authors are sure that they were the first in Hungary to administer anti-oestrogen to patients suffering from IFR. PMID:9262733

  2. Sever's Disease

    MedlinePLUS

    ... pretty frightening, Sever's disease is really a common heel injury that occurs in kids. It can be ... inflammation (swelling) of the growth plate in the heel. A growth plate, also called an epiphyseal plate, ...

  3. Kawasaki Disease

    MedlinePLUS

    ... Topics Cardiac Catheterization Chest X Ray Echocardiography Electrocardiogram Vasculitis Send a link to NHLBI to someone by ... disease. It's a form of a condition called vasculitis (vas-kyu-LI-tis). This condition involves inflammation ...

  4. Gaucher disease

    MedlinePLUS

    ... harmful substances to build up in the liver, spleen, bones, and bone marrow. These substances prevent cells ... common. It involves bone disease, anemia, an enlarged spleen and low platelets (thrombocytopenia). Type I affects both ...

  5. Whipworm Disease

    MedlinePLUS

    ... Tools Print this page Get email updates Order publications Volunteer for Clinical Studies Help people who are suffering from whipworm by volunteering for NIAID clinical studies on ClinicalTrials.gov . Related Links Parasitic Roundworm Diseases National Library of Medicine, ...

  6. Pneumococcal Disease

    MedlinePLUS

    ... information on enabling JavaScript. Pneumococcal Disease Skip Content Marketing Share this: Main Content Area Streptococcus Pneumoniae Streptococcus pneumoniae are bacteria frequently found in the upper respiratory tract of healthy children and adults. These bacteria, however, can also cause ...

  7. Krabbe Disease

    MedlinePLUS

    ... laboratories at the NIH and also supports additional research through grants to major medical institutions across the country. NIH Patient Recruitment for Krabbe Disease Clinical Trials At NIH Clinical Center Throughout the U.S. ...

  8. Sandhoff Disease

    MedlinePLUS

    ... laboratories at the NIH and also supports additional research through grants to major medical institutions across the country. NIH Patient Recruitment for Sandhoff Disease Clinical Trials At NIH Clinical Center Throughout the U.S. ...

  9. Chronic Diseases

    Microsoft Academic Search

    Sharon R. Schatz

    Although diabetes mellitus, cardiovascular disease, and human immunodeficiency virus infection are three separate entities,\\u000a each has causal and non-causal risk factors that are common in the stage 5 chronic kidney disease population. The medical\\u000a nutrition therapies are similar, which emphasize adequate protein and energy intakes, fluid control, and possibly carbohydrate\\u000a and fat modifications. Each patient requires an individualized evaluation, taking

  10. Méničre Disease

    Microsoft Academic Search

    Iee-Ching Wu Anderson; John P. Carey; Walter Kutz; William H. Slattery

    A computerized PubMed search of MEDLINE 1966-May 2005 was performed. The terms “Meniere disease” and “gentamicin” were exploded,\\u000a and the resulting articles were combined. The terms “intratympanic” and “transtympanic” were entered as text words as the\\u000a search term “intratympanic OR transtympanic,” and the results were combined with the Méničre disease\\/gentamicin articles.\\u000a The resulting 136 articles were limited to the English

  11. Celiac Disease

    Microsoft Academic Search

    Sheila E. Crowe

    Celiac disease, also known as celiac sprue or gluten-sensitive enteropathy, is a chronic disorder that is readily recognized\\u000a when it presents in its classical form with diarrhea, bloating, flatulence, weight loss and evidence of malabsorption. However,\\u000a non-gastrointestinal GI and non-specific GI manifestations are currently the more common presentations of this disease. Withdrawal\\u000a of gluten from the diet results in a

  12. Celiac disease

    Microsoft Academic Search

    Debbie Williamson; Michael N. Marsh

    2002-01-01

    Clinically, celiac disease has always been regarded as a wasting, malabsorptive disorder due to disease of the small intestinal\\u000a mucosa. It has been difficult for clinicians to recognize that this condition is primarily due to sensitization of mesenteric\\u000a T lymphocytes to wheat protein (gluten) in genetically predisposed (DQ2+) individuals. On contact with dietary-derived gluten in the upper intestine, these sensitized

  13. Graves’ Disease

    Microsoft Academic Search

    Simon H. S. Pearce

    Hyperthyroid Graves’ disease is one of the commonest autoimmune disorders, affecting about 1% of women. It is most frequent\\u000a in the 4th decade of life. There is a genetic predisposition to Graves’ disease, determined by alleles at the major histocompatibility\\u000a complex (MHC), cytotoxic T-lymphocyte-associated antigen (CTLA-4), protein tyrosine phosphatase non-receptor 22 (PTPN22), and other less well-defined chromosomal loci. Additional, non-genetic,

  14. [Wilson's disease].

    PubMed

    Br?ha, R; Marecek, Z; Martásek, P; Nevsímalová, S; Petrtýl, J; Urbánek, P; Kalistová, H; Pospísilová, L

    2009-01-01

    Wilson's disease is an inherited disorder leading to accumulation of copper in tissues, mainly in the liver and brain. Genetic defect is in the gene coding ATPase type P (ATP7B). The inheritance is autosomal recessive. Up to now, more then 500 mutations causing Wilson's disease were described. The most frequent mutation in Central Europe is mutation H1069Q. The manifestation of Wilson's disease is usually hepatic or neurologic. Hepatic form is manifested by acute or chronic hepatitis, steatosis or cirrhosis. Neurologic involvement is manifested usually after 20 year of age by motor disturbances (tremor, disturbed speech, problems with writing), which could progress into severe extrapyramidal syndrome with tremor, rigidity, dysartria, dysfagia and muscle contracture. Diagnosis is based on clinical and laboratory examinations (neurologic symptoms, liver disease, low serum ceruloplasmin levels, elevated free copper concentration in serum, high urine copper excretion, and presence of Kayser-Fleischer rings). Confirmation of diagnosis is done by hepatic copper concentration in liver biopsy or by genetic examination. Untreated disease leads to the death of a patient. Treatment is based on chelating agents decreasing the copper content by excretion into urine (D-penicillamine, trientine) or on agents preventing absorption of copper from food (zinc, ammonium-tetrahiomolybdene). Patients with asymptomatic Wilson's disease have to be treated as well. In Czech Republic either penicillamine or zinc are used. Liver transplantation is indicated in patients with fulminant liver failure or decompensated cirrhosis. Screening in families of affected patients (all siblings) is obvious. PMID:20662462

  15. Disease mongering.

    PubMed

    Shankar, P R; Subish, P

    2007-04-01

    Convincing healthy people that they are sick and require medicines can enormously expand the market. Disease mongering can turn ordinary ailments like baldness into medical problems, consider risk factors such as hypertension and osteoporosis as diseases and frame prevalence estimates to increase potential markets. In Asia, conditions like erectile dysfunction, male pattern baldness, attention deficit hyperactivity disorder and irritable bowel syndrome, and the drugs to treat them, are widely promoted. Fairness creams and traditional medicines are also widely used. The cost of disease mongering to the individual and the community is expected to be high. Some authors have argued that medicalisation of illnesses may not be a problem and the real problem may be the lack of medicines. Doctors will play a key role in combating disease mongering. Disentanglement from the pharmaceutical industry and development of a capacity for critical analysis are required. Educating patients and empowering them to make decisions are important. Several initiatives have been undertaken to combat disease mongering. Initiatives at the level of the patient and the physician are especially important. Studies on the extent and knowledge of disease mongering among doctors and medical students, and their economic and social consequences are urgently required. PMID:17384871

  16. Pre-transplant thymic function is associated with the risk of cytomegalovirus disease after solid organ transplantation.

    PubMed

    Gracia-Ahufinger, I; Ferrando-Martínez, S; Montejo, M; Muńoz-Villanueva, M C; Cantisán, S; Rivero, A; Solana, R; Leal, M; Torre-Cisneros, J

    2015-05-01

    Cytomegalovirus (CMV) disease is an important complication in solid organ transplant recipients. Thymic function in adults is associated with specific T-cell immunity. Pre-transplant thymic function was analysed in 75 solid organ transplant patients by the use of nested PCR. The primary outcome was the incidence of CMV disease 12 months after transplantation. Using multivariable logistic regression, we studied whether pre-transplant thymic function is an independent risk factor for CMV disease after transplantation. Thymic function was related to the risk of CMV disease in CMV-seropositive recipients. In these recipients, pre-transplant thymic function of <9.5 (OR 11.27, 95% CI 1.11-114.43, p 0.040) and the use of thymoglobulin (OR 8.21, 95% CI 1.09-61.84, p 0.041) were independent risk factors for CMV disease at 12 months after transplantation. Patients with pre-transplant thymic function values of <9.5 had a higher subsequent incidence of CMV disease (24%) than patients with values of ?9.5 (3%) (log-rank test: 5.727; p 0.017). The positive and negative predictive values of these pre-transplant thymic function cut-offs were 0.24 (95% CI 0.10-0.45) and 0.97 (95% CI 0.82-1.00), respectively. Pre-transplant thymic function in CMV-seropositive candidates could be useful in determining the risk of post-transplant CMV disease in solid organ transplant patients, selecting a group of low-risk candidates. PMID:25682299

  17. Behcet's disease.

    PubMed

    Suzuki Kurokawa, M; Suzuki, N

    2004-09-01

    Behcet's disease (BD) is a systemic disorder of recurrent acute inflammation, characterized by major symptoms of oral aphthous ulcers, uveitis, skin lesions and genital ulcers. Involvement of intestines, vessels, and central nervous system (CNS) sometimes leads to a poor prognosis. Patients with BD are known to distribute along the ancient Silk Road. The incidence is relatively higher from eastern Asia to the Mediterranean area as roughly 1-10 patients in 10,000 people, whereas only 1-2 patients in 1,000,000 people in UK and North America. Although etiology of the disease is still unknown, high prevalence of HLA-B51, increased expression of heat shock protein 60 and Th1 dominant immune responses in the patients are considered important in its pathogenesis. Non-infectious neutrophil activation and infection with Streptococcus sanguis and herpes simplex virus would also be associated. Because BD lacks any pathognomonic symptoms and laboratory findings, the diagnosis relies largely upon the criteria proposed by the International Study Group for Behcet's disease in 1990. In Japan, the diagnosis was also made according to the Japanese criteria revised in 1987. Recently, the Behcet's Disease Research Committee of Japan again revised the Japanese criteria in 2003 to avoid overdiagnosis. The new Japanese criteria are introduced in this review. Differential diagnosis excluding Sweet's disease, pemphigus, erythema nodosum and Crohn's disease is important, and positive laboratory data for pathergy test, prick test for dead Streptococci and HLA-B51 are emphasized to make appropriate diagnosis in these criteria. Pathological findings of the disease-affected site such as erythematous nodosum is also stressed. Treatment for the disease has been chosen according to the clinical symptoms. Non-steroidal anti-inflammatory drugs, immunosuppressants, corticosteroids and colchicine are basically introduced. Recently, effects of interferon-alpha/beta, anti-tumor necrosis factor antibody and thalidomide are encouraging, specifically in treatment for the cases with poor prognosis including eye, intestine, vessel and CNS involvement. Low dose weekly administration of methotraxate looks effective for the cases with CNS involvement. Further studies for elucidation of the etiology, improvement of the diagnostic criteria and development of new therapy are needed to conquer the disease. PMID:15598081

  18. Wilson's disease.

    PubMed

    Loudianos, G; Lepori, M B; Mameli, E; Dessě, V; Zappu, A

    2014-01-01

    (Full text is available at http://www.manu.edu.mk/prilozi). Wilson's disease (WD) is a disorder of copper transport resulting from the defective function of a copper transporting P-type ATPase, ATP7B. The WD incidence is approximately 1/50-10,000 live births worldwide. Clinical manifestations of WD may be of any kind, but usually the symptoms of presentation are hepatic or neuropsychiatric, with a vast range of disturbances for both groups of symptoms. In children, however, clinical symptoms may be absent, making the diagnosis of the disease more difficult than in adults. Hepatic manifestations may range from asymptomatic minor biochemical disturbances, to acute, but mostly chronic, hepatitis, cirrhosis or severe fulminant hepatic failure. The spectrum of neurological manifestations is wide, including tremor, hypersalivation, Dysarthria, coordination defects, dystonia, ataxia. The spectrum of psychiatric manifestations is considerable and may include different disturbances such as altered working performance, anxiety, depression and antisocial behaviour. Kayser-Fleischer rings (KF) are present in 95% of patients with neurological symptoms and somewhat over half of those without neurological symptoms. In children presenting with liver disease, KF rings are usually absent. To obtain a more reliable diagnosis of WD, the Leipzig scoring system was proposed by an international consensus of experts. Wilson's disease copper overload is treated with chelating agents such as penicillamine, trientine and tetrathiomolybdate. Zinc is used mostly for mantainance therapy or the treatment of asymptomatic WD patients. Key words: Wilson diseases, copper, cirrhosis, children. PMID:24798599

  19. Fabry's disease.

    PubMed

    El-Abassi, Rima; Singhal, Divya; England, John D

    2014-09-15

    Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the GLA gene, which leads to a deficiency in ?-galactosidase A. The abnormal accumulation of glycosphingolipids, primarily globotriaosylceramide, manifests as serious and progressive impairment of renal and cardiac functions. In addition, patients experience pain, gastrointestinal disturbance, transient ischemic attacks and strokes. Disease presentation in female heterozygotes may be as severe as in males although women may also remain asymptomatic. This review covers all basic aspects of the disease such as epidemiology, pathophysiology, clinical presentation by systems, diagnosis, management, prevention, and repercussions on quality of life. With the development of enzyme replacement therapy in the past few years, early initiation of treatment was found to be key for reduction of disease burden in major affected organs with improvement in neuropathic pain, decreased cardiac mass and stabilization of renal function, gastrointestinal symptoms, and hearing. This review aims to raise the awareness of the signs and symptoms of Fabry's disease as well as to provide guidelines for the diagnosis and treatment. PMID:25106696

  20. Whipple's disease.

    PubMed

    Laeeq, Syed Mudassir; Luck, Nasir Hassan; Hassan, Syed Mujahid; Abbas, Zaigham; Tasneem, Abbas Ali; Mubarak, Muhammed

    2014-05-01

    Whipple's disease is a rare chronic multi-systemic infection, caused by Gram-positive bacillus Tropheryma whipplei. The infection usually involves the small bowel, but other organs may also be involved. The diagnosis is often challenging and can only be made on histopathological examination. This report describes 2 patients presenting with abdominal pain and weight loss who finally were diagnosed to have Whipple's disease. One of the patients was a renal transplant recipient. To the best of authors' knowledge, no case of Whipple's disease has yet been reported in Pakistan. The diagnosis were made on the basis of histopathological evaluation of duodenal biopsies. The cases underscore the need for diligent histopathological evaluation of the upper gastrointestinal biopsies and a high index of suspicion for an accurate diagnosis of the condition. The approach to the diagnosis and management of the condition is discussed. PMID:24906280

  1. Crohn's Disease

    NSDL National Science Digital Library

    Patient Education Institute

    This patient education program explains Crohn's Disease, one of the most common inflammatory bowel diseases, including the symptoms, diagnosis, and treatment options. It also reviews the anatomy of the gastrointestinal system, causes of the disease, dietary triggers, and pregnancy in the Crohn's patient. This resource is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: This tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

  2. KSHV-associated multicentric Castleman disease: A tangle of different entities requiring multitarget treatment strategies.

    PubMed

    Carbone, Antonino; De Paoli, Paolo; Gloghini, Annunziata; Vaccher, Emanuela

    2015-07-15

    Multicentric Castleman Disease (MCD) is a lymphoproliferative disorder presenting with heterogeneous pathological and clinical features. It comprises disease entities with a complex aetiology and overlapping pathogenesis. MCD can be found in association with HIV infection, plasma-cell dyscrasias, Kaposi sarcoma (KS), B-cell lymphomas including primary effusion lymphoma (PEL) and its solid variant, and Hodgkin lymphoma. In KSHV-associated MCD cases, a common association is KS and a specific variant of lymphoma referred to as "plasmablastic lymphoma," also called "large B-cell lymphoma arising in KSHV-associated MCD" lacking EBV infection. MCD is often referred to as human interleukin-6 (hIL-6) syndrome, since an overproduction of IL-6 occurs in MCD-associated diseases as well as in MCD itself. hIL-6 and a viral IL-6 (vIL-6) homolog encoded by KSHV can independently or together lead to flares of KSHV-associated MCD. Recently, a new clinical entity was proposed to describe a severe systemic infection/reactivation of KSHV: KSHV inflammatory syndrome (KICS). KICS may contribute in inducing the inflammatory symptoms seen in some patients with severe KS or PEL. The precise relationship of KICS to KSHV-associated MCD is unclear and it is possible that KICS may be prodromal symptoms to frank KSHV-associated MCD. Options for treatment of KSHV-associated MCD and related diseases include monoclonal antibodies, chemotherapy, immune modulators, virus-activated cytotoxic therapy and antiviral therapies. A comprehensive understanding of the intricacies of the HIV-KSHV coinfection will probably lead to additional advances in therapy and managements for these disorders. PMID:24771491

  3. Hirayama disease.

    PubMed

    Huang, Yen-Lin; Chen, Chi-Jen

    2011-11-01

    Hirayama disease (juvenile muscular atrophy of distal upper extremity) is a cervical myelopathy. Predominantly affecting male adolescents, it is characterized by progressive muscular weakness and atrophy of distal upper limbs, followed by spontaneous arrest within several years. Although the cause of cervical myelopathy remains unclear, neuropathologic and neuroradiologic findings suggest a forward displacement of the posterior cervical dural sac during neck flexion, causing compression of the cervical cord, and results in atrophic and ischemic changes in the anterior horn. A good understanding of Hirayama disease is essential because early recognition and management can effectively halt the progressive deterioration. PMID:22032508

  4. Behçet's disease

    PubMed Central

    Kontogiannis, V; Powell, R

    2000-01-01

    Behçet's disease is a systemic vasculitis of unknown aetiology characteristically affecting venules. Onset is typically in young adults with recurrent oral and genital ulceration, uveitis, skin manifestations, arthritis, neurological involvement, and a tendency to thrombosis. It has a worldwide distribution but is prevalent in Japan, the Middle East, and some Mediterranean countries. International diagnostic criteria have been proposed, however diagnosis can be problematical, particularly if the typical ulcers are not obvious at presentation. Treatment is challenging, must be tailored to the pattern of organ involvement for each patient and often requires combination therapies.???Keywords: Behçet's disease; oral ulcers; uveitis; immunosuppressants PMID:11009577

  5. Dent's disease.

    PubMed

    Devuyst, Olivier; Thakker, Rajesh V

    2010-01-01

    Dent's disease is a renal tubular disorder characterized by manifestations of proximal tubule dysfunction, including low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure. These features are generally found in males only, and may be present in early childhood, whereas female carriers may show a milder phenotype. Prevalence is unknown; the disorder has been reported in around 250 families to date. Complications such as rickets or osteomalacia may occur. The disease is caused by mutations in either the CLCN5 (Dent disease 1) or OCRL1 (Dent disease 2) genes that are located on chromosome Xp11.22 and Xq25, respectively. CLCN5 encodes the electrogenic Cl?/H(+) exchanger ClC-5, which belongs to the CLC family of Cl? channels/transporters. OCRL1 encodes a phosphatidylinositol bisphosphate (PIP?) 5-phosphatase and mutations are also associated with Lowe Syndrome. The phenotype of Dent's disease is explained by the predominant expression of ClC-5 in the proximal tubule segments of the kidney. No genotype-phenotype correlation has been described thus far, and there is considerable intra-familial variability in disease severity. A few patients with Dent's disease do not harbour mutations in CLCN5 and OCRL1, pointing to the involvement of other genes. Diagnosis is based on the presence of all three of the following criteria: low-molecular-weight proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, kidney stones, hematuria, hypophosphatemia or renal insufficiency. Molecular genetic testing confirms the diagnosis. The differential diagnosis includes other causes of generalized dysfunction of the proximal tubules (renal Fanconi syndrome), hereditary, acquired, or caused by exogenous substances. Antenatal diagnosis and pre-implantation genetic testing is not advised. The care of patients with Dent's disease is supportive, focusing on the treatment of hypercalciuria and the prevention of nephrolithiasis. The vital prognosis is good in the majority of patients. Progression to end-stage renal failure occurs between the 3rd and 5th decades of life in 30-80% of affected males. PMID:20946626

  6. Fungal Diseases

    MedlinePLUS

    ... Ask your pediatrician for a referral to a pediatric infectious disease specialist if your youngster is diagnosed with one ... B. Last Updated 5/5/2015 Source Immunizations ... © 2006 American Academy of Pediatrics) The information contained on this Web site should ...

  7. Smelling Diseases

    NSDL National Science Digital Library

    Science Update

    2004-06-14

    We all use our noses to make quick judgments from time to time -- whether it's checking to see if the milk's still good, or if a shirt needs to go in the wash. Now, doctors are developing a kind of sniff test to screen for diseases. Find out more in this Science Update.

  8. Newcastle disease

    Microsoft Academic Search

    Dennis J. Alexander

    2001-01-01

    1. In this paper several historical and contemporary aspects of Newcastle disease (ND) are reviewed, with particular reference to the greater understanding which modern techniques have allowed. 2. Virulent ND viruses were generally thought to have emerged in 1926 as a result of transfer from a wild bird host reservoir but there is evidence that the virulent virus may have

  9. Prionic diseases.

    PubMed

    Araújo, Abelardo Q-C

    2013-09-01

    Prion diseases are neurodegenerative illnesses due to the accumulation of small infectious pathogens containing protein but apparently lacking nucleic acid, which have long incubation periods and progress inexorably once clinical symptoms appear. Prions are uniquely resistant to a number of normal decontaminating procedures. The prionopathies [Kuru, Creutzfeldt-Jakob disease (CJD) and its variants, Gerstmann-Sträussler-Scheinker (GSS) syndrome and fatal familial insomnia (FFI)] result from accumulation of abnormal isoforms of the prion protein in the brains of normal animals on both neuronal and non-neuronal cells. The accumulation of this protein or fragments of it in neurons leads to apoptosis and cell death. There is a strong link between mutations in the gene encoding the normal prion protein in humans (PRNP) - located on the short arm of chromosome 20 - and forms of prion disease with a familial predisposition (familial CJD, GSS, FFI). Clinically a prionopathy should be suspected in any case of a fast progressing dementia with ataxia, myoclonus, or in individuals with pathological insomnia associated with dysautonomia. Magnetic resonance imaging, identification of the 14-3-3 protein in the cerebrospinal fluid, tonsil biopsy and genetic studies have been used for in vivo diagnosis circumventing the need of brain biopsy. Histopathology, however, remains the only conclusive method to reach a confident diagnosis. Unfortunately, despite numerous treatment efforts, prionopathies remain short-lasting and fatal diseases. PMID:24141515

  10. Dent's disease

    Microsoft Academic Search

    Olivier Devuyst; Rajesh V. Thakker

    2010-01-01

    Dent's disease is a renal tubular disorder characterized by manifestations of proximal tubule dysfunction, including low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure. These features are generally found in males only, and may be present in early childhood, whereas female carriers may show a milder phenotype. Prevalence is unknown; the disorder has been reported in around 250 families to

  11. Infectious Diseases

    NSDL National Science Digital Library

    NBC Learn

    2010-10-07

    With the threat of a warmer, wetter world and a larger global population, scientists are researching how climate change may impact the spread of infectious diseases,ťsuch as cholera and dengue fever, and how outbreaks may be prevented.ť "Changing Planet" is produced in partnership with the National Science Foundation.

  12. Celiac disease.

    PubMed

    Green, Peter H R; Lebwohl, Benjamin; Greywoode, Ruby

    2015-05-01

    This review will focus on the pathogenesis, clinical manifestations, diagnosis, and management of celiac disease (CD). Given an increasing awareness of gluten-related disorders, medical professionals of all varieties are encountering patients with a diagnosis of CD or who are thought to have food intolerance to gluten. The prevalence of CD among the general population is estimated to be 1% in Western nations, and there is growing evidence for underdiagnosis of the disease, especially in non-Western nations that were traditionally believed to be unaffected. The development of serologic markers specific to CD has revolutionized the ability both to diagnose and monitor patients with the disease. Additionally, understanding of the clinical presentations of CD has undergone a major shift over the past half century. Although it is well understood that CD develops in genetically predisposed subjects exposed to gluten, the extent of other environmental factors in the pathogenesis of the disease is an area of continued research. Currently, the main therapeutic intervention for CD is a gluten-free diet; however, novel nondietary agents are under active investigation. Future areas of research should also help us understand the relationship of CD to other gluten-related disorders. PMID:25956012

  13. Zoonotic Diseases

    MedlinePLUS

    ... such as unpasteurized milk, undercooked meat, or unwashed fruits and vegetables that are contaminated with feces from an infected animal) Luckily, there are many ways you can protect yourself and your family from zoonotic diseases. You can: Always wash hands and follow proper ...

  14. Avocado diseases

    Microsoft Academic Search

    G. A. Zentmyer

    1984-01-01

    Several fungi can cause diseases of avocado (Persea americana (Mill.)) of which Phytophthora cinnamomi Rands is the most serious. Phytophthora root rot causes extensive losses of avocado trees in nearly every country where avocados are grown. The fungus can be isolated from soil and roots by using selective agar media containing antibiotic chemicals and by using various types of baits

  15. Diverticular Disease

    MedlinePLUS

    ... disease may be caused by not eating enough fiber. When you don't eat enough fiber, you may get constipated and your stools may ... your doctor may suggest that you eat more fiber, drink plenty of fluids and exercise regularly to ...

  16. The Power and the Promise of Restimulation-Induced Cell Death in Human Immune Diseases

    PubMed Central

    Snow, Andrew L.; Pandiyan, Pushpa; Zheng, Lixin; Krummey, Scott M.; Lenardo, Michael J.

    2010-01-01

    Summary Controlled expansion and contraction of lymphocytes both during and after an adaptive immune response is imperative to sustaining a healthy immune system. Both extrinsic and intrinsic pathways of lymphocyte apoptosis are programmed to eliminate cells at the proper time to ensure immune homeostasis. Genetic disorders of apoptosis described in mice and humans have established Fas and Bim as critical pro-apoptotic molecules responsible for T-cell death in response to T-cell receptor restimulation and cytokine withdrawal, respectively. Emerging evidence prompts revision of this classic paradigm, especially for our understanding of restimulation-induced cell death (RICD) and its physiological purpose. Recent work indicates that RICD employs both Fas and Bim for T-cell deletion, dispelling the notion that these molecules are assigned to mutually exclusive apoptotic pathways. Furthermore, new mouse model data combined with our discovery of defective RICD in X-linked lymphoproliferative disease (XLP) patient T cells suggest RICD is essential for precluding excess T-cell accumulation and associated immunopathology during the course of certain infections. Here we review how these advances offer a refreshing new perspective on the phenomenon of T-cell apoptosis induced through antigen restimulation, including its relevance to immune homeostasis and potential for therapeutic interventions. PMID:20636809

  17. Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease.

    PubMed

    Uldrick, Thomas S; Polizzotto, Mark N; Aleman, Karen; Wyvill, Kathleen M; Marshall, Vickie; Whitby, Denise; Wang, Victoria; Pittaluga, Stefania; O'Mahony, Deirdre; Steinberg, Seth M; Little, Richard F; Yarchoan, Robert

    2014-12-01

    Kaposi sarcoma (KS) herpesvirus-associated multicentric Castleman disease (KSHV-MCD) is a lymphoproliferative disorder, most commonly seen in HIV-infected patients, that has a high mortality if untreated. Concurrent KS is common. Although rituximab has reported activity in KSHV-MCD, its use is often associated with KS progression. Within a natural history study of KSHV-MCD, we prospectively evaluated rituximab 375 mg/m(2) combined with liposomal doxorubicin 20 mg/m(2) (R-Dox) every 3 weeks in 17 patients. Patients received a median of 4 cycles (range 3-9). All received antiretroviral therapy, 11 received consolidation interferon-?, and 6 received consolidation high-dose zidovudine with valganciclovir. Using NCI KSHV-MCD response criteria, major clinical and biochemical responses were attained in 94% and 88% of patients, respectively. With a median 58 months' potential follow-up, 3-year event-free survival was 69% and 3-year overall survival was 81%. During R-Dox therapy, cutaneous KS developed in 1 patient, whereas 5 of 6 patients with it had clinical improvement. R-Dox was associated with significant improvement in anemia and hypoalbuminemia. KSHV viral load, KSHV viral interleukin-6, C-reactive protein, human interleukin-6, and serum immunoglobulin free light chains decreased with therapy. R-Dox is effective in symptomatic KSHV-MCD and may be useful in patients with concurrent KS. This trial was registered at www.clinicaltrials.gov as #NCT00092222. PMID:25331113

  18. Coronary heart disease

    MedlinePLUS

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... Coronary heart disease (CHD) is the leading cause of death in the United States for men and women. Coronary ...

  19. Diabetic Heart Disease

    MedlinePLUS

    ... from the NHLBI on Twitter. What Is Diabetic Heart Disease? The term "diabetic heart disease" (DHD) refers ... Kidney Diseases' Introduction to Diabetes Web page. What Heart Diseases Are Involved in Diabetic Heart Disease? DHD ...

  20. Chronic Kidney Disease (CKD)

    MedlinePLUS

    ... www.kidneyfund.org > Kidney Disease > Chronic Kidney Disease Chronic Kidney Disease (CKD) An estimated 31 million people in the United ... living with chronic kidney disease (CKD). What is CKD? The term “chronic kidney disease” (CKD) means lasting ...

  1. HIV and Rheumatic Disease

    MedlinePLUS

    ... Patient Resources > Diseases & Conditions Back to Diseases & Conditions HIV and Rheumatic Disease PRINT Download PDF HIV infection ... treatment and HIV infection all overlap. What are HIV-associated rheumatic diseases? Some diseases of the joints ...

  2. Measurement of minimal residual disease before and after myeloablative hematopoietic cell transplantation for acute leukemia.

    PubMed

    Appelbaum, Frederick R

    2013-09-01

    Multiparameter flow cytometry (MFC) can identify leukemia-associated immunophenotypes in more than 90% of cases of acute leukemia with detection limits of 10(-3)-10(-4). In order to better understand the potential utility of MFC to measure minimal residual disease (MRD) in the setting of myeloablative hematopoietic cell transplantation (HCT), we studied cohorts of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in complete remission (CR) both pre- and post-HCT. Among 253 patients with AML, the 3-year estimates of overall survival were 73% (CR1) and 73% (CR2) for those who were MRD(neg) and 32% (CR1) and 44% (CR2) for those who were MRD(pos), with relapse rates being more than doubled in those who were MRD(pos) pre-HCT (21% vs 58% for CR1 patients and 19% vs 68% for CR2 patients). The presence of MRD anytime during the first 100 days post-HCT predicted a 6-fold higher risk of subsequent relapse. In 157 patients with ALL, the 3-year overall survivals were 68% for the MRD(neg) cohort vs 40% for those who were MRD(pos) pre-HCT, with probabilities of relapse of 16% in those who were MRD(neg) vs 33% in the MRD(pos) group. As in AML, the presence of MRD in the post-transplant setting indicated that the risk of subsequent relapse was high, but not inevitable. PMID:24309531

  3. Genetic mapping of quantitative trait loci affecting susceptibility to Marek's disease virus induced tumors in F2 intercross chickens.

    PubMed Central

    Vallejo, R L; Bacon, L D; Liu, H C; Witter, R L; Groenen, M A; Hillel, J; Cheng, H H

    1998-01-01

    Marek's disease (MD) is a lymphoproliferative disease caused by the MD virus (MDV), which costs the poultry industry nearly $1 billion annually. To identify quantitative trait loci (QTL) affecting MD susceptibility, the inbred lines 6(3) (MD resistant) and 7(2) (MD susceptible) were mated to create more than 300 F2 chickens. The F2 chickens were challenged with MDV JM strain, moderately virulent) at 1 wk of age and assessed for MD susceptibility. The QTL analysis was divided into three stages. In stage 1, 65 DNA markers selected from the chicken genetic maps were typed on the 40 most MD-susceptible and the 40 most MD-resistant F2 chickens, and 21 markers residing near suggestive QTL were revealed by analysis of variance (ANOVA). In stage 2, the suggestive markers plus available flanking markers were typed on 272 F2 chickens, and three suggestive QTL were identified by ANOVA. In stage 3, using the interval mapping program Map Manager and permutation tests, two significant and two suggestive MD QTL were identified on four chromosomal subregions. Three to five loci collected explained between 11 and 23% of the phenotypic MD variation, or 32-68% of the genetic variance. This study constitutes the first report in the domestic chicken on the mapping of non-major histocompatibility complex QTL affecting MD susceptibility. PMID:9475745

  4. Fabry disease

    PubMed Central

    2010-01-01

    Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal ?-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual ?-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal ?-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked ?-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human ?-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones. PMID:21092187

  5. Gaucher disease.

    PubMed

    Mignot, Cyril; Gelot, Antoinette; De Villemeur, Thierry Billette

    2013-01-01

    Gaucher disease is an autosomal recessive condition due to glucocerebrosidase deficiency responsible for the lysosomal accumulation of glucosylceramide, a complex lipid derived from cell membranes, mainly in macrophages. It is due to mutations mostly in the GBA gene, although saposine C deficiency is due to mutations in the PSAP gene. It encompasses an extremely heterogeneous spectrum of clinical involvement from the fetus to adulthood. Splenomegaly, blood cytopenia, and bone involvement are the main manifestations of Gaucher disease, but nervous system degeneration is observed in about 5-10% of patients. The accumulation in neurons of glucosylceramide and its derivative, psychosine, are thought to underlie neuronal dysfunction and death, although Gaucher cells that mostly accumulate such substances are mainly macrophages. Enzyme replacement therapy dramatically improves the outcome of patients because of its extreme efficacy in the treatment of the systemic involvement. However, it has only limited effects on most neurological signs. PMID:23622393

  6. Morgellons disease?

    PubMed

    Accordino, Robert E; Engler, Danielle; Ginsburg, Iona H; Koo, John

    2008-01-01

    Morgellons disease, a pattern of dermatologic symptoms very similar, if not identical, to those of delusions of parasitosis, was first described many centuries ago, but has recently been given much attention on the internet and in the mass media. The present authors present a history of Morgellons disease, in addition to which they discuss the potential benefit of using this diagnostic term as a means of building trust and rapport with patients to maximize treatment benefit. The present authors also suggest "meeting the patient halfway" and creating a therapeutic alliance when providing dermatologic treatment by taking their cutaneous symptoms seriously enough to provide both topical ointments as well as antipsychotic medications, which can be therapeutic in these patients. PMID:18318880

  7. Adenotonsillar Disease

    Microsoft Academic Search

    David H. Darrow; Nathan A. Kludt

    \\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Tonsils and adenoid are important sources of J-chain bearing B-cell precursors that can eventually bind secretory IgA.\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Although most tonsillitis in children is viral, Group A streptococcal disease is the most common treatable disorder. Treatment\\u000a is useful primarily in the prevention of sequelae. Tonsillectomy, however, may reduce the frequency of Group A streptococcal\\u000a disease in selected individuals with

  8. Thyroid disease

    SciTech Connect

    Falk, S.

    1990-01-01

    Presenting a multidisciplinary approach to the diagnosis and treatment of thyroid disease, this volume provides a comprehensive picture of current thyroid medicine and surgery. The book integrates the perspectives of the many disciplines that deal with the clinical manifestations of thyroid disorders. Adding to the clinical usefulness of the book is the state-of-the-art coverage of many recent developments in thyroidology, including the use of highly sensitive two-site TSH immunoradionetric measurements to diagnose thyroid activity; thyroglobulin assays in thyroid cancer and other diseases; new diagnostic applications of MRI and CT; treatment with radionuclides and chemotherapy; new developments in thyroid immunology, pathology, and management of hyperthyroidism; suppressive treatment with thyroid hormone; and management of Graves' ophthalmopathy. The book also covers all aspects of thyroid surgery, including surgical treatment of hyperthyroidism; papillary, follicular, and other carcinomas; thyroidectomy; and prevention and management of complications.

  9. [Wilsons disease].

    PubMed

    Mare?ek, Z; Br?ha, R

    2013-07-01

    Wilsons disease is an autosomal recessive genetic disorder in which copper accumulates in tissues, especially in the liver and the brain. The genetic defect affects the P type ATPase gene (ATP7B). More than 500 mutations causing Wilsons disease have been described. The most common mutation in Central Europe concerns H1069Q. The symptoms of Wilsons disease include hepatic or neurological conditions. The hepatic condition is manifested as steatosis, acute or chronic hepatitis or cirrhosis. The neurological conditions are most often manifested after the age of 20 as motor disorders (tremor, speech and writing disorders), which may result in severe extrapyramidal syndrome with rigidity, dysarthria and muscle contractions. The dia-gnosis is based on clinical and laboratory assessments (neurological signs, liver lesions, low ceruloplasmin, increased free serum copper, high Cu volumes in urine, KayserFleischer ring). The dia-gnosis is confirmed by a high Cu level in liver tissue or genetic proof. Untreated Wilsons disease causes death of the patient. If treated properly the survival rate approximates to the survival rate of the common population. The treatment concerns either removal of copper from the body using chelating agents excreted into the urine (Penicillamine, Trientine) or limitation of copper absorption from the intestine and reducing the toxicity of copper (zinc, ammonium tetrathiomolybdate). In the Czech Republic, Penicillamine or zinc is used. A liver transplant is indicated in patients with fulminant hepatic failure or decompensated liver cirrhosis. In the family all siblings of the affected individual need to be screened in order to treat any asymptomatic subjects. PMID:23909262

  10. Stargardt Disease

    Microsoft Academic Search

    Rando Allikmets

    When the adenosine triphosphate (ATP)-binding cassette (ABC) transporter gene, ABCA4 (originally named ABCR), was cloned and characterized in 1997 as the causal gene for autosomal recessive Stargardt disease (arSTGD or STGD1) (1) it seemed as if just another missing link was added to the extensive table of genetic determinants of rare monogenic retinal\\u000a dystrophies. Now, 9 yr later, the ABCA4

  11. Celiac Disease

    Microsoft Academic Search

    Stefano Guandalini

    \\u000a Celiac disease (CD) is an autoimmune disorder occurring in genetically susceptible individuals, triggered by gluten and related\\u000a prolamins, and plant storage proteins found in wheat, barley, and rye. It affects primarily the small intestine, where it\\u000a progressively leads to flattening of the small intestinal mucosa and subsequent nutrient malabsorption. Its pathogenesis involves\\u000a interactions among genetic, environmental, and immunological factors. Well-identified

  12. Huntington's Disease

    Microsoft Academic Search

    Seymour Gendelman; Howard E. Gendelman; Tsuneya Ikezu

    Huntington’s disease (HD) is a familial and rare inherited neurological disorder with a prevalence of 5–8 cases per 100,000\\u000a worldwide. This makes HD the most common inherited neurodegenerative disorder (Fahn, 2005). HD is passed from parent to child\\u000a in autosomal dominant fashion. Each child of an HD parent has a 50% chance of inheriting HD. Both sexes are affected equally.

  13. Plant Disease Lesson: Dutch elm disease

    NSDL National Science Digital Library

    Cleora J. D'Arcy (University of Illinois; )

    2000-07-21

    This plant disease lesson on Dutch elm disease (caused by the fungus Ophiostoma ulmi) includes information on symptoms and signs, pathogen biology, disease cycle and epidemiology, disease management, and the significance of the disease. Selected references are listed and a glossary is also available for use with this resource.

  14. Plant Disease Lesson: Rhizoctonia Diseases of Turfgrass

    NSDL National Science Digital Library

    Lane P. Tredway (University of Georgia, Athens; )

    2001-11-09

    This plant disease lesson on Rhizoctonia diseases of turfgrass (caused by the fungi Rhizoctonia species) includes information on symptoms and signs, pathogen biology, disease cycle and epidemiology, disease management, and the significance of the disease. Selected references are listed and a glossary is also available for use with this resource.

  15. Plant Disease Lesson: Lesion nematode disease

    NSDL National Science Digital Library

    Eric L. Davis (North Carolina State University; )

    2000-10-30

    This plant disease lesson on Lesion nematode disease (caused by Pratylenchus) includes information on symptoms and signs, pathogen biology, disease cycle and epidemiology, disease management, and the significance of the disease. Selected references are listed and a glossary is also available for use with this resource.

  16. Plant Disease Lesson: Soybean cyst nematode disease

    NSDL National Science Digital Library

    Eric L. Davis (North Carolina State University; )

    2000-07-25

    This plant disease lesson on Soybean cyst nematode disease (caused by Heterodera glycines) includes information on symptoms and signs, pathogen biology, disease cycle and epidemiology, disease management, and the significance of the disease. Selected references are listed and a glossary is also available for use with this resource.

  17. Significance of Ethnicity in the Risk of Acute Graft-versus-Host Disease and Leukemia Relapse after Unrelated Donor Hematopoietic Stem Cell Transplantation

    PubMed Central

    Morishima, Yasuo; Kawase, Takakazu; Malkki, Mari; Morishima, Satoko; Spellman, Stephen; Kashiwase, Koichi; Kato, Shunichi; Cesbron, Anne; Tiercy, Jean-Marie; Senitzer, David; Velardi, Andrea; Petersdorf, Effie W.

    2014-01-01

    The significance of patient and donor ethnicity on risk of acute graft-versus-host disease (GVHD) and disease relapse after unrelated donor hematopoietic cell transplantation (HCT) is not known. A total of 4335 patient/donor pairs from the International Histocompatibility Working Group in HCT met the following three criteria: (1) HLA-A, B, C, DRB1 and DQB1 allele matched donor; (2) diagnosis of leukemia, and (3) non-T cell depleted GVHD prophylaxis. Post-transplant risks of acute GVHD and leukemia relapse were defined in Asian/Pacific Islander, Caucasian, African American, Hispanic, and Native American patients transplanted from donors with the same self-described background. Asian patients had a significantly lower incidence of acute GVHD (Japanese patients: 40.0% grades II-IV and 15.3% grades III-IV; non-Japanese Asian patients: 42.1% grades II-IV and 15.7% grades III-IV) compared to Caucasian patients (56.5% grades II-IV and 22.6% grades III-IV) (p< 0.001). The hazard ratio (HR) of acute GVHD for Caucasian patients was significantly higher than for Japanese patients. Unexpectedly, the HR of leukemia relapse in Caucasian patients with early disease status was also significantly higher than that in Japanese patients. These results provide a platform for future investigation into the genetic factors for unrelated donor HCT and clinical implications of diverse ethnic background. PMID:23747601

  18. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.

    PubMed

    Holler, Ernst; Butzhammer, Peter; Schmid, Karin; Hundsrucker, Christian; Koestler, Josef; Peter, Katrin; Zhu, Wentao; Sporrer, Daniela; Hehlgans, Thomas; Kreutz, Marina; Holler, Barbara; Wolff, Daniel; Edinger, Matthias; Andreesen, Reinhard; Levine, John E; Ferrara, James L; Gessner, Andre; Spang, Rainer; Oefner, Peter J

    2014-05-01

    Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 ?mol/L to 11.8 ± 2.8 ?mol/L in all post-transplant samples and to 3.5 ± 3 ?mol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT. PMID:24492144

  19. Posttransplant Recurrent FSGS: Molecular Insights and Future Directions

    Microsoft Academic Search

    Asher D. Schachter; Terry B. Strom

    1999-01-01

    Focal-segmental glomerulosclerosis (FSGS) is the most common glomerular cause of renal failure in children and after transplantation is associated with a significantly increased risk of renal allograft loss [1]. Recurrence of FSGS following transplantation occurs in 15–50% of the cases [2–10]. The median time to recurrence is 14 days after transplantation [7], suggesting a role for a systemic abnormality or

  20. Early use of plasmapheresis for recurrent post-transplant FSGS

    Microsoft Academic Search

    Madhura Pradhan; Julie Petro; Joanne Palmer; Kevin Meyers; H. Jorge Baluarte

    2003-01-01

    Recurrence of focal segmental glomerulosclerosis (FSGS) in an allograft is a challenging clinical situation because it frequently results in graft loss. We report our experience with early use of plasmapheresis in recurrent FSGS. Of the 18 (33%) children with biopsy-proven FSGS (in their native kidneys) transplanted at our institution, 6 had recurrence (elevated urine protein\\/creatinine ratios) post transplant and were

  1. Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis

    PubMed Central

    Shatat, Ibrahim F.; Skversky, Amy L.; Woroniecki, Robert P.; Del Rio, Marcela; Perelstein, Eduardo M.; Johnson, Valerie L.; Mahesh, Shefali

    2012-01-01

    Background Focal segmental glomerulosclerosis (FSGS) recurs in 20–40 % of allografts. Plasmapheresis (TPE) has been one of the mainstays of treatment with variable results. Rituximab (RTX), a monoclonal antibody to the protein CD20, is being used for treatment of recurrent FSGS (recFSGS) but pediatric experience is limited. Methods We conducted a retrospective review of eight patients with recFSGS, treated with RTX (1–4 doses) after having minimal response to TPE. Complete response was defined as a decrease in urine protein creatinine ratio (Up/c) to less than 0.2 and partial response was a decrease in Up/c ratio by 50 % of baseline and in the sub-nephrotic range (U p/c <2). Results Complete response was seen in two of eight patients, and partial response was seen in four of eight patients. Two patients had no response. At last follow-up, all the partial responders had sub-nephrotic range proteinuria (Up/c ratios ranging from 0.29 to 1.6). Delayed response, up to 9 months post-RTX, was also seen in some of the patients. Significant complications such as rituximab-associated lung injury (RALI), acute tubular necrosis, and central nervous system (CNS) malignancy were also observed in our case series. Conclusions Rituximab can be used with caution as a treatment for recFSGS. Efficacy is variable from none to complete response. Even partial reduction in proteinuria is of benefit in prolonging the life of the allograft. Long-term, multicenter studies are needed to prove its sustained efficacy in those who respond and to monitor for serious adverse effects. PMID:23052653

  2. [Morton's disease].

    PubMed

    Isomoto, Shinji; Tanaka, Yasuhito

    2014-12-01

    Morton's disease refers to neuralgia at the web space of the toes with a pseudo-neuroma. It commonly occurs in the third web space of the foot in middle-aged and older women. The pseudo-neuroma is thought to be a secondary change after entrapment or repeated microtrauma. Patients complain of forefoot pain while walking. Typically, symptoms are caused by tight high-heeled shoes. The physical examination includes palpation of the web spaces and Mulder's test. Weight bearing foot radiographs are used to evaluate the deformity of the foot, especially at metatarsophalangeal (MTP) joints. MRI is useful for differential diagnosis of pseudo-neuroma, MTP joint arthritis, and interdigital bursitis. Conservative treatments are shoe modification, use of orthotic insoles, and injection of corticosteroids and local anesthesia. The injections are useful not only for the treatment but also for diagnosis of Morton's disease. If the local injection is not temporally effective, surgical treatment is not indicated. If the conservative treatment fails, surgical treatment is indicated. The most common surgery is excision of the pseudo-neuroma. The surgery is usually performed using a dorsal approach. PMID:25475032

  3. Chagas' disease.

    PubMed Central

    Tanowitz, H B; Kirchhoff, L V; Simon, D; Morris, S A; Weiss, L M; Wittner, M

    1992-01-01

    Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS. Images PMID:1423218

  4. Vibration disease.

    PubMed

    Kákosy, T

    1989-04-01

    Today, in this age of technology, vibration caused by machinery is an almost universal hazard. Vibration transferred from a machine to the human body may cause discomfort, a reduction of performance, and even injury. Vibratory manual tools may cause damage to the circulatory system of the upper extremities (Raynaud's syndrome), to the peripheral nerves (peripheral neuropathy), and to the bones and joints (aseptic necrosis, fatigue fractures, degenerative joint disease). Vehicles and machines causing floor vibration cause degenerative disc disease of the lumbar spine. The pathogenesis of vibration injuries is still not completely clear and there is no effective treatment. Some of the abnormalities are irreversible and may cause permanent decrease of working ability, and even unemployment. This is why prevention is so important. Prevention is complex, including technical and organizational measures, use of individual protective clothing and footwear, and medical supervision both before and during employment. Workers who are exposed to vibration should be protected against other aggravating factors such as cold and noise, etc. Vibration-induced injuries are recognized in law in many countries as grounds for financial compensation. Their cost to industry is rising and, unless a means of prevention or cure is found, will continue to do so in the foreseeable future. PMID:2661029

  5. Disease Activity Measures in Paediatric Rheumatic Diseases

    PubMed Central

    Luca, Nadia J.; Feldman, Brian M.

    2013-01-01

    Disease activity refers to potentially reversible aspects of a disease. Measurement of disease activity in paediatric rheumatic diseases is a critical component of patient care and clinical research. Disease activity measures are developed systematically, often involving consensus methods. To be useful, a disease activity measure must be feasible, valid, and interpretable. There are several challenges in quantifying disease activity in paediatric rheumatology; namely, the conditions are multidimensional, the level of activity must be valuated in the context of treatment being received, there is no gold standard for disease activity, and it is often difficult to incorporate the patient's perspective of their disease activity. To date, core sets of response variables are defined for juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, and juvenile dermatomyositis, as well as definitions for improvement in response to therapy. Several specific absolute disease activity measures also exist for each condition. Further work is required to determine the optimal disease activity measures in paediatric rheumatology. PMID:24089617

  6. What Is Hodgkin Disease?

    MedlinePLUS

    ... the key statistics about Hodgkin disease? What is Hodgkin disease? Hodgkin disease (Hodgkin lymphoma) is a type of ... also have lymphoid tissue. Start and spread of Hodgkin disease Because lymphoid tissue is in many parts of ...

  7. Wheat Diseases Atlas. 

    E-print Network

    McCoy, Norman L.; Berry, Robert W.

    1982-01-01

    CONTENTS INTRODUCTION ........................ . DISSEMINATION OF WHEAT DISEASES ... . ROOT DISEASES ......................... . Root, Crown and Foot Rots ............... . Plant Parasitic Nematodes ................ . Seedling Diseases... . . . . . . . . . . . . . . . . . . . . . . . . . FOLIAGE DISEASES ..................... . 3 3 4 4 4 4 5 Rusts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Leaf Rust . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Stem Rust...

  8. Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)

    ClinicalTrials.gov

    2012-07-03

    Myelodysplastic and Myeloproliferative Disorders; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Multiple Myeloma; Plasma Cell Dyscrasia; Lymphoproliferative Disorders; Hematologic Diseases

  9. `Silk Route Disease' (Behçet's Disease)

    PubMed Central

    James, D. Geraint

    1988-01-01

    Behçet's disease is a multisystem disorder in which orogenital ulceration is associated with troublesome generalized uveitis, erythema nodosum, pyoderma, dermatographism, seronegative arthritis, and neurologic and cardiovascular symptoms. There is no diagnostic laboratory test; the diagnosis is based on the disorder's multisystem clinical features. A points scoring system is helpful in distinguishing it from other multisystem disorders that mimic it. It occurs most frequently in an area coinciding with the old Silk Route, between latitudes 30° and 45° north, in Asian and Eurasian populations, and it has an HLA-B51 affinity. The cause remains unknown, but a postulated trigger factor is a herpesvirus with cofactors that include ethnic group, human leukocyte antigen affinities, T-cell and autonomic imbalance, circulating immune complexes, autoimmunity, blood viscosity, decreased fibrinolysis, and zinc deficiency. Treatment includes administering corticosteroids, azathioprine, chlorambucil, cyclosporine, and colchicine, and fibrinolytic therapy. PMID:3291395

  10. Insertion of reticuloendotheliosis virus long terminal repeat into the genome of CVI988 strain of Marek's disease virus results in enhanced growth and protection.

    PubMed

    Lupiani, Blanca; Lee, Lucy F; Kreager, K S; Witter, Richard L; Reddy, Sanjay M

    2013-06-01

    Marek's disease (MD) is a lymphoproliferative disease of chickens caused by serotype 1 MD virus (MDV). Vaccination of commercial poultry has drastically reduced losses from MD, and the poultry industry cannot be sustained without the use of vaccines. Retrovirus insertion into herpesvirus genomes is an efficient process that alters the biological properties of herpesviruses. RM1, a virus derived from the virulent JM strain of MDV, by insertion of the reticuloendotheliosis (REV) long terminal repeat (LTR), was attenuated for oncogenicity but retains properties of the parental virus, such as lymphoid organ atrophy. Here we show that insertion of the REV LTR into the genome of vaccine strain CVI988 resulted in a virus (CVRM) that replicated to higher levels than parental CVI988 in cell culture and that remained apathogenic for chickens. In addition, CVRM showed protection indices similar or superior to those afforded by CVI988 virus in laboratory and field protection trials, indicating that it could be developed as a safe and efficacious vaccine to protect against very virulent plus MDV. PMID:23901756

  11. Parkinson's disease.

    PubMed

    Benninger, David H

    2013-01-01

    In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses therapeutic challenges. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in noninvasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, although whether a causal interaction exists remains largely undetermined. Most trials of noninvasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS), targeting the motor cortex. Current studies suggest a possible therapeutic potential for rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible with regard to functional independence and quality of life. Approaches to potentiate the efficacy of rTMS include increasing stimulation intensity and novel stimulation parameters that derive their rationale from studies on brain physiology. These novel parameters are intended to simulate normal firing patterns or to act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia with regard to motor control and its contribution to the pathogenesis of motor disorders. Noninvasive brain stimulation studies will enhance our understanding of PD pathophysiology and might provide further evidence for potential therapeutic applications. PMID:24112916

  12. Progression of cardiac allograft vascular disease as assessed by serial intravascular ultrasound: correlation to immunological and non-immunological risk factors

    PubMed Central

    Pethig, K; Klauss, V; Heublein, B; Mudra, H; Westphal, A; Weber, C; Theisen, K; Haverich, A

    2000-01-01

    OBJECTIVE—To characterise the severity and progression of cardiac allograft vascular disease (CAVD) in a large patient cohort, and to evaluate possible immunological and non-immunological risk factors for progression.?DESIGN—A prospective observational study using intravascular ultrasound.?SETTING—Two university hospitals.?PATIENTS AND MAIN OUTCOME MEASURES—Changes in focal plaque, lumen, and total vessel area (worst site method) were assessed at baseline and after 12.1 (2.8) months (mean (SD)) of follow up in a cohort of 96 patients (79 male, 17 female; mean age 48.7 (9.6) years; time post-transplant 26.0 (32.4) months).?RESULTS—Overall, the mean (SD) intimal index of worst sites increased by 6.7 (8.8)%. The increase in the first 12 months was 7.5 (9.4)%, v 5.9 (8.0)% after the first year (NS). Analysing immunological and non-immunological risk factors (age, underlying disease, sex, donor age, immunosuppression, cytomegalovirus, rejection episodes, cholesterol), low density lipoprotein (LDL) cholesterol was found to be the most important predictor of severe progression (as defined by an increase in intimal index of ? 15% (p = 0.01).?CONCLUSIONS—Progression of CAVD is characterised by a continuing increase in intimal hyperplasia, especially within the first year after heart transplantation. LDL cholesterol is an important predictor of major progression.???Keywords: heart transplantation; cardiac allograft vasculopathy; intravascular ultrasound PMID:11040007

  13. Rice Diseases Atlas.

    E-print Network

    Walla, Walter

    1977-01-01

    . 448. au., S.H. 1972 Rice Diseases. Eastern Press Ltd., London and Reading, England. Whitney, N. G. and Richard A. Frederiksen, 1975 Kernel Smut of Rice. Texas Agricultural Experiment Station Bulletin MP-1231. (Blank Page in Original Bulletin... CONTENTS INTRODUCTION .......... . .. . ........ . SEEDLI NG DISEASES ... . ... . .. . ........ . FOLIAGE DISEASES ................... .. SHEATH AND STEM DISEASES .......... . DISEASES ATT ACKI NG THE KERNEL ..... . PHYSIOLOGICAL Di...

  14. RARE DISEASES LIST

    EPA Science Inventory

    The rare disease list includes rare diseases and conditions for which information requests have been made to the Office of Rare Diseases. A rare disease is defined as a disease or condition for which there are fewer than 200,000 affected persons alive in the United States. The Of...

  15. Diabetic Heart Disease

    MedlinePLUS

    ... heart disease (CHD), heart failure, and diabetic cardiomyopathy. Diabetes by itself puts you at risk for heart disease. Other risk factors include Family history of heart disease Carrying extra ...

  16. Pelvic Inflammatory Disease (PID)

    MedlinePLUS

    ... Pelvic Inflammatory Disease (PID) - CDC Fact Sheet Untreated sexually transmitted diseases (STDs) can cause pelvic inflammatory disease ( ... chlamydia and gonorrhea. Other infections that are not sexually transmitted can also cause PID. How do I ...

  17. Peripheral Vascular Disease

    MedlinePLUS

    ... Arterial blockage including peripheral artery disease or PAD Aortic aneurysms Buerger's Disease Raynaud's Phenomenon Disease of the veins ... blood to flow around, or "bypass," the blockage. Aortic Aneurysms An aneurysm is a balloon-like bulge in ...

  18. Types of Periodontal Disease

    MedlinePLUS

    Types of Periodontal Disease Gingivitis Chronic Periodontitis Aggressive Periodontitis Periodontitis Caused by Conditions of the Body Necrotizing Periodontal Diseases Periodontal disease can refer to any condition that affects the gums and ...

  19. Digestive Diseases Materials

    MedlinePLUS

    ... NIDDK Health Information NIDDK Home NIDDK Image Library Digestive Disease, Nutrition, and Weight-control Materials Healthy eating, ... Materials Statistics Tip Sheets Catalog Home | Diabetes Materials | Digestive Diseases Materials | Kidney and Urologic Diseases Materials Online ...

  20. Gum (Periodontal) Disease

    MedlinePLUS

    ... Disease: What Is Gum (Periodontal) Disease? In This Topic What Is Gum (Periodontal) Disease? Risk Factors and ... for More Information National Institute on Aging Related Topics Problems with Taste The information in this topic ...

  1. Kidney disease - resources

    MedlinePLUS

    Resources - kidney disease ... The following organizations are good resources for information on kidney disease: National Kidney Disease Education Program - www.nkdep.nih.gov National Kidney Foundation - www.kidney.org National ...

  2. Heart disease - resources

    MedlinePLUS

    Resources - heart disease ... The following organizations are good resources for information on heart disease: American Heart Association - www.americanheart.org Centers for Disease Control and Prevention - www.cdc.gov/heartdisease/

  3. Lipid Storage Diseases

    MedlinePLUS

    ... of the lipid storage disorders, although Gaucher and Fabry diseases have highly effective enzyme replacement therapies. There is ... from infection or progressive neurological loss. Children with Fabry disease often die prematurely of complications from heart disease, ...

  4. Heart Disease in Women

    MedlinePLUS

    ... page from the NHLBI on Twitter. How Does Heart Disease Affect Women? Espańol In the United States, ... about coronary MVD and broken heart syndrome. Coronary Heart Disease CHD is a disease in which plaque ( ...

  5. Childhood Contagious Diseases

    MedlinePLUS

    ... in children. Hand-Foot-and-Mouth Disease Hand-foot-and-mouth disease is a suddenly appearing (acute), self-limited viral disease caused by viruses of the enterovirus group, particularly Coxsackievirus A16. The ...

  6. Learning about Crohn's Disease

    MedlinePLUS

    ... have a blood relative with some form of inflammatory bowel disease, usually a brother or a sister, and sometimes ... 10 percent chance to develop some form of inflammatory bowel disease. When both parents have inflammatory bowel disease, the ...

  7. Carotid Artery Disease

    MedlinePLUS

    ... HEALTH Carotid Artery Disease What are the carotid arteries? The carotid arteries are the bloodd vessels that ... the back of the brain. What is carotid artery disease? Carotid artery disease is defined by the ...

  8. Ebola Virus Disease

    MedlinePLUS

    Ebola virus disease Fact sheet N°103 Updated April 2015 Key facts Ebola virus disease (EVD), formerly ... live Ebola virus in vaginal secretions. Symptoms of Ebola virus disease The incubation period, that is, the ...

  9. Chronic obstructive pulmonary disease

    MedlinePLUS

    ... airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... a protein called alpha-1 antitrypsin can develop emphysema. Other risk factors for COPD are: Exposure to ...

  10. Biomarker for Glycogen Storage Diseases

    ClinicalTrials.gov

    2015-06-12

    Fructose Metabolism, Inborn Errors; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type VIII

  11. Suppression and reversal of gld disease by parabiosis with normal mice.

    PubMed

    Kakkanaiah, V N; MacDonald, G C; Cohen, P L; Eisenberg, R A

    1996-01-01

    The disruption of the Fas receptor or Fas ligand by the lpr or gld mutations, respectively, results in severe autoimmune and lymphoproliferative disease due to the failure of Fas-mediated deletion of self-reactive lymphocytes. Recently, we have shown in mixed chimeras that gld-induced autoimmunity could be corrected by normal bone marrow, in particular by normal T cells. In contrast, lpr-mediated autoimmunity could not be influenced by normal bone marrow-derived cells. In the present report, we have studied the role of normal lymphocytes in suppressing or reversing gld-induced autoimmunity by parabiosis with normal mice. Our results show a suppression of lymphadenopathy, fewer CD4-CD8- T cells, and lower levels of autoantibody production in gld mice parabiosed with normal mice at 4-6 weeks of age. The gld mice parabiosed with normal mice at 4 months of age also exhibited a substantial reduction of both total and CD4-CD8- T cells in the periphery 2 months after surgery. However, they showed little reduction of autoantibodies compared to gld mice parabiosed with gld mice. In contrast, older lpr mice did not exhibit any reduction in lymphadenopathy or autoantibody production after parabiosis with normal mice. The prevention or reversal of lymphadenopathy in parabiosed gld mice suggests that ongoing Fas-mediated deletion in the periphery may play an important role in maintaining self-tolerance. The relative irreversibility of autoantibody synthesis in older parabiosed gld mice suggests that autoantibody-producing B cells or their committed precursors are long lived and do not express functional Fas receptor. PMID:8599885

  12. Plant Disease Lesson: Blackleg

    NSDL National Science Digital Library

    Gavin Ash (Charles Sturt University; )

    2000-11-11

    This plant disease lesson on Blackleg (caused by Leptosphaeria maculans (teleomorph) Phoma lingam (anamorph).) includes information on symptoms and signs, pathogen biology, disease cycle and epidemiology, disease management, and the significance of the disease. Selected references are listed and a glossary is also available for use with this resource.

  13. The integrated disease network.

    PubMed

    Sun, Kai; Buchan, Natalie; Larminie, Chris; Pržulj, Nataša

    2014-11-01

    The growing body of transcriptomic, proteomic, metabolomic and genomic data generated from disease states provides a great opportunity to improve our current understanding of the molecular mechanisms driving diseases and shared between diseases. The use of both clinical and molecular phenotypes will lead to better disease understanding and classification. In this study, we set out to gain novel insights into diseases and their relationships by utilising knowledge gained from system-level molecular data. We integrated different types of biological data including genome-wide association studies data, disease-chemical associations, biological pathways and Gene Ontology annotations into an Integrated Disease Network (IDN), a heterogeneous network where nodes are bio-entities and edges between nodes represent their associations. We also introduced a novel disease similarity measure to infer disease-disease associations from the IDN. Our predicted associations were systemically evaluated against the Medical Subject Heading classification and a statistical measure of disease co-occurrence in PubMed. The strong correlation between our predictions and co-occurrence associations indicated the ability of our approach to recover known disease associations. Furthermore, we presented a case study of Crohn's disease. We demonstrated that our approach not only identified well-established connections between Crohn's disease and other diseases, but also revealed new, interesting connections consistent with emerging literature. Our approach also enabled ready access to the knowledge supporting these new connections, making this a powerful approach for exploring connections between diseases. PMID:25133803

  14. Autoimmunity in thyroid disease

    Microsoft Academic Search

    Joanne Collins; Stephen Gough

    2002-01-01

    The autoimmune thyroid diseases, Graves' disease and autoimmune hypothyroidism, represent the two ends of a disease spectrum where an immune response is directed against the thyroid gland. In Graves' disease, antibodies directed against the thyrotropin receptor (TSH-R) lead to the development of glandular overactivity, while in autoimmune hypothyroidism, cell-mediated and humoral thyroid injury leads to destruction of thyroid tissue and

  15. Kidney Disease of Diabetes

    E-print Network

    Baker, Chris I.

    Kidney Disease of Diabetes National Kidney and Urologic Diseases Information Clearinghouse is the final stage of chronic kidney disease (CKD). Diabetes is the most common cause of kidney failure, accounting for nearly 44 percent of new cases.1 Even when diabetes is controlled, the disease can lead to CKD

  16. What Is Crohn's Disease?

    MedlinePLUS

    ... belongs to a group of conditions known as Inflammatory Bowel Diseases (IBD). Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract. When reading about inflammatory bowel diseases, it is important to know that Crohn’s disease ...

  17. Variable presence of KITD816V in clonal haematological non-mast cell lineage diseases associated with systemic mastocytosis (SM-AHNMD).

    PubMed

    Sotlar, Karl; Colak, Sema; Bache, Anja; Berezowska, Sabina; Krokowski, Manuela; Bültmann, Burkhard; Valent, Peter; Horny, Hans-Peter

    2010-04-01

    In a substantial number of patients with systemic mastocytosis (SM), an associated clonal haematological non-mast cell lineage disease (AHNMD) is detectable. Although most of these patients display KIT mutations, especially KIT(D816V), little is known about their exact frequency and their distribution in AHNMD subtypes. We examined 48 patients with SM-AHNMD for the presence of mutant KIT in the SM and AHNMD components of the disease. Mast cells and AHNMD cells were obtained from immunostained bone marrow sections by laser microdissection and examined by melting point analysis of nested-PCR products. KIT(D816V) was found in AHNMD cells in the vast majority of patients with SM-chronic myelomonocytic leukaemia (CMML, 89%). Unexpectedly, KIT(D816V) was far less frequently detectable in AHNMD cells in patients with SM-myeloproliferative neoplasm (MPN, 20%) and SM-acute myeloid leukaemia (AML, 30%). None of the patients with lymphoproliferative AHNMDs displayed KIT codon 816 mutations in AHNMD cells (0/8). In FIP1L1/PDGFRA-positive chronic eosinophilic leukaemia (CEL), neither the SM nor the CEL component of the disease exhibited the KIT mutation. Our findings demonstrate that KIT codon 816 mutations are variably present in AHNMD cells in patients with SM-AHNMD, depending on the subtype of AHNMD. The high frequency of KIT(D816V) in neoplastic mast cells and leukaemic myelomonocytic cells in SM-CMML may point to a common precursor in these patients, and may have implications for the biology of the disease and the development of KIT-targeting therapies. PMID:20112369

  18. Multicentric Castleman’s Disease and Kaposi’s Sarcoma in a HIV-Positive Patient on Highly Active Antiretroviral Therapy

    PubMed Central

    Ortega, Lauro; Cooper, Chad J.; Otoukesh, Salman; Mojtahedzadeh, Mona; Didia, Claudia S.; Torabi, Alireza; Nahleh, Zeina

    2014-01-01

    Castleman’s disease is a group of rare lymphoproliferative disorders. The plasmablastic multicentric Castleman’s disease is frequently discovered in HIV-infected individuals in association with Kaposi sarcoma (HHV-8). Thirty-five year old male presented to our care with the main compliant of severe back pain for one week. His past medical problems include acquired immune deficiency syndrome diagnosed 12 years prior and Kaposi sarcoma, currently on highly active antiretroviral therapy (HAART). Radiographic imaging revealed hepatomegaly and diffuse lymphadenopathy. The HIV viral load was <20 polymerase chain reaction copies/mL, absolute CD4 count was 453 cells/mcL (490-1740 cells/mcL) and CD8 count was 4142 cells/mcL (180-1170 cells/ mcL). Excisional biopsy of the left supraclavicular lymph node was performed with pathological findings of HHV8+ Kaposi sarcoma in the background of multicentric Castleman’s disease (plasmacytic variant). No evidence of transformation into large B-cell or plasmablastic lymphoma was noted. He was discharged on HAART and follow up to receive chemotherapy with cyclophosphamide, adriamycin, vincristine plus prednisone was started and rituximab plus prophylaxis for pneumocystis carinii. Multicentric Castleman’s disease has become more relevant in recent years due to its association with HIV and HHV-8 (Kaposi sarcoma) and its potential to progress into plasmablastic B-cell lymphoma. The progression of MCD to B-cell lymphoma is a concern, especially in patients with HIV infection because it precludes the worst outcome and a high mortality, despite treatment. The most intriguing part of this case is that MCD occurred in a HIV-positive on HAART. This case signals a warning that a high suspicion for MCD can be justified even in those HIV-positive patients on HAART because the possibly of progression to plasmablastic B-cell lymphoma. PMID:25276327

  19. Oral Crohn's disease

    PubMed Central

    Padmavathi, BN; Sharma, Smriti; Astekar, Madhusudan; Rajan, Y; Sowmya, GV

    2014-01-01

    ’Crohn's disease’ is an inflammatory granulomatous disease of the gastrointestinal tract with extra-intestinal manifestations. Oral lesions may precede the intestinal disease and serve as a source for histological diagnosis. We present a case of orofacial Crohn's disease where orofacial symptoms were present for about 13 years and occasional constipation was present, since 6 months. Oral examination plays an important role in early diagnosis of Crohn's disease. PMID:25364165

  20. Epstein-Barr virus reactivation in allogeneic stem cell transplantation is highly related to cytomegalovirus reactivation.

    PubMed

    Zallio, Francesco; Primon, Valeria; Tamiazzo, Stefania; Pini, Massimo; Baraldi, Anna; Corsetti, Maria T; Gotta, Franca; Bertassello, Claudia; Salvi, Flavia; Rocchetti, Andrea; Levis, Alessandro

    2013-01-01

    Monitoring of Epstein-Barr virus (EBV) load and pre-emptive rituximab is an appropriate approach to prevent post-transplant lymphoproliferative disease (PTLD) occurring after hematopoietic stem cell transplantation (HSCT). This pre-emptive approach, based on EBV-DNA monitoring through a quantitative polymerase chain reaction, was applied to 101 consecutive patients who underwent allo HSCT at our Institute (median age 50). A single infusion of rituximab was administered to 11 of 16 patients who were at high risk for progression to PTLD, defined as a DNA value >10 000 copies/mL. All patients cleared EBV DNAemia, without any recurrences. Main factors significantly associated with high risk for PTLD were as follows: (i) unrelated vs. sibling (26% vs. 7%; p = 0.011); (ii) T-cell depletion (29% vs. 6%; p = 0.001); (iii) graft versus host disease (GVHD; 30% vs. 7%; p = 0.002); and (iv) cytomegalovirus (CMV) reactivation (29% vs. 4%; p = 0.001). Multivariate analysis showed that CMV reactivation was the only independent variable associated with EBV reactivation. We conclude that: (i) a single infusion of rituximab is able to prevent the risk of progression into EBV-related PTLD; and (ii) CMV reactivation is strongly associated with EBV reactivation; therefore, an intensive EBV monitoring strategy could be advisable only in case of CMV reactivation. PMID:23781897

  1. Prion diseases as transmissible zoonotic diseases.

    PubMed

    Lee, Jeongmin; Kim, Su Yeon; Hwang, Kyu Jam; Ju, Young Ran; Woo, Hee-Jong

    2013-02-01

    Prion diseases, also called transmissible spongiform encephalopathies (TSEs), lead to neurological dysfunction in animals and are fatal. Infectious prion proteins are causative agents of many mammalian TSEs, including scrapie (in sheep), chronic wasting disease (in deer and elk), bovine spongiform encephalopathy (BSE; in cattle), and Creutzfeldt-Jakob disease (CJD; in humans). BSE, better known as mad cow disease, is among the many recently discovered zoonotic diseases. BSE cases were first reported in the United Kingdom in 1986. Variant CJD (vCJD) is a disease that was first detected in 1996, which affects humans and is linked to the BSE epidemic in cattle. vCJD is presumed to be caused by consumption of contaminated meat and other food products derived from affected cattle. The BSE epidemic peaked in 1992 and decreased thereafter; this decline is continuing sharply owing to intensive surveillance and screening programs in the Western world. However, there are still new outbreaks and/or progression of prion diseases, including atypical BSE, and iatrogenic CJD and vCJD via organ transplantation and blood transfusion. This paper summarizes studies on prions, particularly on prion molecular mechanisms, BSE, vCJD, and diagnostic procedures. Risk perception and communication policies of the European Union for the prevention of prion diseases are also addressed to provide recommendations for appropriate government policies in Korea. PMID:24159531

  2. MOLECULAR AND CELLULAR BIOLOGY, July 2005, p. 61786198 Vol. 25, No. 14 0270-7306/05/$08.00 0 doi:10.1128/MCB.25.14.61786198.2005

    E-print Network

    Monnat, Ray

    of Newcastle upon Tyne Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom8/lymphoma (ATLL), an aggressive lymphoproliferative disease that is often fatal. Here, we demonstrate T cells and causes adult T-cell leukemia/lymphoma (ATLL), an aggressive lymphoproliferative disease

  3. Lyme Disease Research

    NSDL National Science Digital Library

    Maine Medical Center Research Institute's Lyme Disease Research Laboratory provides this website focusing on ticks and the control of tick-borne diseases. This site is divided into several sections. The first section "Tick Borne Diseases" contains resources on diseases caused by tick-borne pathogens, such as Lyme disease. "Prevention & Control" gives site visitors information on avoiding tick bites, and removal of ticks from the body. Links to other sites and key sources of information on ticks and Lyme disease can be found in the "Other Resources" section.

  4. Epidemiology: Understanding Disease Spread

    NSDL National Science Digital Library

    Marion Fass (Beloit College; Biology)

    2006-05-20

    Factors that influence disease spread throughout populations can be explored with the program Epidemiology. Both population and disease characteristics can be modeled over different time periods. The Susceptible- Infected- Recovered (SIR) model enables us to make predictions based on significant variables such as the flow of new susceptibles in to the population, transmission rates, disease deaths, and the duration of the disease. Ebola is used as a model organism and epidemiology is presented from both a microbiological and social perspective. * build epidemiological models of different diseases, design strategies for disease control, and test the effectiveness of these strategies on virtual populations

  5. Lymphoproliferative responses after infection with human parvovirus B19.

    PubMed Central

    von Poblotzki, A; Gerdes, C; Reischl, U; Wolf, H; Modrow, S

    1996-01-01

    Immunity after infection with the parvovirus B19 is assumed to be conferred by a humoral immune response with development of neutralizing antibody. In contrast, little is known about the nature of T-cell-mediated responses to parvovirus B19 infection in humans. We used recombinant proteins VP1, VP2, and NS1, as well as a recombinant VP1-specific amino-terminal sequence, to test the proliferative responses of peripheral blood mononuclear cells after infection of otherwise healthy individuals with parvovirus B19. These proteins were used as antigens for the stimulation of freshly isolated cells. The results show that a B19 virus-specific cellular immunity develops that is directed against the capsid proteins VP1 and VP2. We also demonstrate that viral determinants are presented to CD4+ T cells by HLA class II molecules. PMID:8794392

  6. Congenital heart disease

    MedlinePLUS

    ... Down syndrome Marfan syndrome Noonan syndrome Trisomy 13 Turner syndrome Often, no cause for the heart disease ... good control over their blood sugar levels. Certain genes may play a role in congenital heart disease. ...

  7. Liver Disease and IBD

    MedlinePLUS

    ... 34% of Crohn’s patients with disease of the terminal ileum (the last segment of the small intestine). ... increased risk for developing gallstones because the diseased terminal ileum cannot absorb bile salts, which are necessary ...

  8. Fibrocystic breast disease

    MedlinePLUS

    Miltenburg DM, Speights VO Jr. Benign breast disease. Obstet Gynecol Clin North Am . 2008;35:285-300. Katz VL, ... malignant disease. In: Lentz GM, Lobo RA, Gershenson DM, Katz VL, eds. Comprehensive Gynecology . 6th ed. Philadelphia, ...

  9. Lou Gehrig's Disease (ALS)

    MedlinePLUS

    ... 10% will survive more than 10 years. Stephen Hawking has been living with Lou Gehrig's disease for ... term survivor of the disease. Born in England, Hawking is a famous physicist who furthered our understanding ...

  10. Pediatric inflammatory bowel disease

    PubMed Central

    Diefenbach, Karen A; Breuer, Christopher K

    2006-01-01

    Inflammatory bowel disease is an important cause of gastrointestinal pathology in children and adolescents. The incidence of pediatric inflammatory bowel disease is increasing; therefore, it is important for the clinician to be aware of the presentation of this disease in the pediatric population. Laboratory tests, radiology studies, and endoscopic procedures are helpful in diagnosing inflammatory bowel disease and differentiating between Crohn’s disease and ulcerative colitis. Once diagnosed, the goal of medical management is to induce remission of disease while minimizing the side effects of the medication. Specific attention needs to be paid to achieving normal growth in this susceptible population. Surgical management is usually indicated for failure of medical management, complication, or malignancy. Algorithms for diagnostic evaluation and treatment of pediatric inflammatory bowel disease are presented. The specific psychosocial issues facing these patients are also discussed in this review as are the future goals of research in the complex problem of pediatric inflammatory bowel disease. PMID:16718840

  11. Creutzfeldt-Jakob Disease

    MedlinePLUS

    Creutzfeldt-Jakob disease (CJD) is a rare, degenerative brain disorder. Symptoms usually start around age 60. Memory problems, behavior changes, vision ... during a medical procedure Cattle can get a disease related to CJD called bovine spongiform encephalopathy (BSE) ...

  12. Tay-Sachs Disease

    MedlinePLUS

    Tay-Sachs disease is a rare, inherited disorder. It causes too much of a fatty substance to build up in the ... mental and physical problems. Infants with Tay-Sachs disease appear to develop normally for the first few ...

  13. Cat Scratch Disease

    MedlinePLUS

    Cat scratch disease (CSD) is an illness caused by the bacterium Bartonella henselae. Almost half of all cats carry the infection ... symptoms of CSD, call your doctor. Centers for Disease Control and Prevention

  14. Carotid Artery Disease

    MedlinePLUS

    ... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...

  15. Sexually Transmitted Diseases

    MedlinePLUS

    Sexually transmitted diseases (STDs) are infections that you can get from having sex with someone who has the infection. The causes ... is no cure. Sometimes medicines can keep the disease under control. Correct usage of latex condoms greatly ...

  16. Bile Duct Diseases

    MedlinePLUS

    ... carry the bile to your small intestine. Different diseases can block the bile ducts and cause a ... liver failure. A rare form of bile duct disease called biliary atresia occurs in infants. It is ...

  17. Pelvic Inflammatory Disease

    MedlinePLUS

    Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...

  18. Paget's Disease of Bone

    MedlinePLUS

    ... What is Paget's Disease of Bone? In This Topic What is Paget's Disease of Bone? Symptoms and ... for More Information National Institute on Aging Related Topics Osteoarthritis Eating Well as You Get Older More ...

  19. Carotid artery disease

    MedlinePLUS

    ... artery disease may be a stroke or a transient ischemic attack (TIA). A TIA is a small ... Major complications of carotid artery disease are: Transient ischemic ... vessel to the brain. It causes the same symptoms as stroke. ...

  20. Liver disease - resources

    MedlinePLUS

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation - www.liverfoundation.org Children's Liver Association for Support Services - www.classkids.org Hepatitis ...

  1. Lung disease - resources

    MedlinePLUS

    Resources - lung disease ... The following organizations are good resources for information on lung disease : American Lung Association - www.lungusa.org National Heart, Lung, and Blood Institute - www.nhlbi.nih.gov ...

  2. Lyme disease (image)

    MedlinePLUS

    ... that is caused by the bacterium Borrelia burgdorferi . Lyme disease is transmitted by the bite of a deer tick. Symptoms resolve in 3 to 4 weeks even without treatment, but secondary or tertiary disease may develop if ...

  3. Heart Valve Disease

    MedlinePLUS

    ... from the NHLBI on Twitter. What Is Heart Valve Disease? Heart valve disease occurs if one or ... ability to pump blood. Overview How the Heart Valves Work At the start of each heartbeat, blood ...

  4. Sickle Cell Disease (SCD)

    MedlinePLUS

    ... inherited two hemoglobin S genes, is the most common form of sickle cell disease. There are variations on SCD where the patient inherits one hemoglobin S gene with another hemoglobin problem that results in a disease similar to classic ...

  5. Dejerine-Sottas Disease

    MedlinePLUS

    ... the genes for proteins found in myelin, a coating on axons that insulates and nourishes them. DS ... combat these effects. Disease: Peripheral Neuropathies Charcot-Marie-Tooth Disease (CMT) Hereditary Motor and Sensory Neuropathy (Charcot- ...

  6. What Causes Heart Disease?

    MedlinePLUS

    ... page from the NHLBI on Twitter. What Causes Heart Disease? Research suggests that coronary heart disease (CHD) ... Red: Eileen's Story 04/10/2014 Celebrating American Heart Month: NIH Advancing Heart Research 02/06/2014 ...

  7. Living with Heart Disease

    MedlinePLUS

    ... page from the NHLBI on Twitter. Living With Heart Disease If you have coronary heart disease (CHD), ... it harder for you to make lifestyle changes. Heart Attack Warning Signs If you have CHD, learn ...

  8. Diabetic Eye Disease

    MedlinePLUS

    ... los Ojos Cómo hablarle a su oculista Diabetic Eye Disease Listen View this module and educate yourself, family, and friends about diabetic eye disease. This module includes descriptive audio and captioning. Diabetic ...

  9. Coronary Heart Disease

    MedlinePLUS

    ... from the NHLBI on Twitter. What Is Coronary Heart Disease? Espańol Coronary heart disease (CHD) is a ... Red: Eileen's Story 04/10/2014 Celebrating American Heart Month: NIH Advancing Heart Research 02/06/2014 ...

  10. Learning about Your Disease

    MedlinePLUS

    ... for you. Tweet Learning about your disease Acute Lymphoblastic Leukemia (ALL) Acute myelogenous leukemia (AML) Adrenoleukodystrophy (ALD) Chronic Lymphocytic Leukemia (CLL) Chronic myelogeneous leukemia (CML) Hodgkin lymphoma Hurler syndrome Krabbe disease (GLD) Metachromatic leukodystrophy (MLD) ...

  11. Men and Heart Disease

    MedlinePLUS

    ... this? Submit What's this? Submit Button Related CDC Web Sites Heart Disease Stroke High Blood Pressure Salt ... this? Submit What's this? Submit Button Related CDC Web Sites Heart Disease Stroke High Blood Pressure Salt ...

  12. Heart Disease Risk Factors

    MedlinePLUS

    ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

  13. Women and Heart Disease

    MedlinePLUS

    ... this? Submit What's this? Submit Button Related CDC Web Sites Heart Disease Stroke High Blood Pressure Salt ... this? Submit What's this? Submit Button Related CDC Web Sites Heart Disease Stroke High Blood Pressure Salt ...

  14. Learning about Huntington's Disease

    MedlinePLUS

    ... the symptoms and progression of the disease by breeding laboratory animals, such as mice, and attempting to ... Center (HDAC) Web site by focusing on the science of HD. Huntington Disease [rarediseases.info.nih.gov] ...

  15. Sickle Cell Disease

    MedlinePLUS

    ... to help you deal with the disease. Strong family relationships and close personal friends can be helpful. A support group can also help you cope with the disease. Work with your family doctor to set goals for coping with your ...

  16. Pregnancy and Fifth Disease

    MedlinePLUS

    ... Cheek Rash Parvovirus B19 and Other Illnesses References Pregnancy and Fifth Disease Recommend on Facebook Tweet Share ... with fifth disease. Testing for Parvovirus B19 During Pregnancy A blood test for parvovirus B19 can show ...

  17. Carotid Artery Disease

    MedlinePLUS

    ... from the NHLBI on Twitter. What Is Carotid Artery Disease? Carotid (ka-ROT-id) artery disease is ... blood to your face, scalp, and neck. Carotid Arteries Figure A shows the location of the right ...

  18. Coronary Artery Disease

    MedlinePLUS

    Coronary artery disease (CAD) is the most common type of heart disease. It is the leading cause of death ... both men and women. CAD happens when the arteries that supply blood to heart muscle become hardened ...

  19. Undifferentiated Connective Tissue Disease

    MedlinePLUS

    ... vessels. Examples of connective tissue diseases include lupus , scleroderma , rheumatoid arthritis , Sjögren's syndrome , myositis , and vasculitis . There ... connective tissue diseases, such as lupus, Sjögren's or scleroderma. More UCTD Information Causes Diagnosis Symptoms Treatment Print ...

  20. Blood and Lymph Diseases

    MedlinePLUS

    ... Medicine, National Institutes of Health. National Center for Biotechnology Information (US). Genes and Disease [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show ...

  1. Cat scratch disease (image)

    MedlinePLUS

    Cat scratch disease is an infectious illness associated with cat scratches, bites, or exposure to cat saliva, causing chronic swelling of the lymph nodes. Cat scratch disease is possibly the most common cause of chronic ...

  2. Cat scratch disease

    MedlinePLUS

    ... scratch disease is caused by Bartonella henselae . The disease is spread through contact with an infected cat (a bite or scratch). It also can be spread through contact with cat saliva on broken skin or mucosal surfaces like those ...

  3. Detection and differentiation of CVI988 (Rispens vaccine) from other serotype 1 Marek's disease viruses.

    PubMed

    Gimeno, Isabel M; Dunn, John R; Cortes, Aneg L; El-Gohary, Abd El-Galil; Silva, Robert F

    2014-06-01

    The serotype 1 Marek's disease virus (MDV) is the causative agent for Marek's disease (MD), a lymphoproliferative disease of chickens of great concern to the poultry industry. CVI988 (Rispens vaccine), an attenuated serotype 1 MDV, is currently the most efficacious commercially available vaccine for preventing MD. However, it is difficult to detect and differentiate CVI988 when other serotype 1 MDVs are present. To facilitate the detection of CVI988, we developed two sets of primers for a mismatch amplification mutation assay (MAMA) PCR that targeted the single nulceotide polymorphism associated with the H19 epitope of the phosphorylated protein 38 gene. The PCR was very specific. One primer set (oncogenic primers) amplified DNA from 15 different serotype 1 MDVs except CVI988. The other primer set (CVI988 primers) amplified DNA from CVI988 but not from any of the other 15 serotype 1 MDVs. A real-time PCR assay was developed using MAMA primers, and specificity and sensitivity was evaluated in vitro and in vivo. Mixtures of plasmids (CVI988 plasmid and oncogenic plasmid) at various concentrations were used to evaluate the sensitivity/specificity of MAMA primers in vitro. Both primer setswere able to amplify as little as one copy of their respective plasmid. Oncogenic primers were highly specific and only amplified CVI988 plasmid when the concentration of oncogenic plasmid was very low (1 X 10(1)) and CVI988 plasmid was very high (1 X 10(6)). Specificity of CVI988 primers was not as high because they could amplify oncogenic plasmids when the concentration of CVI988 plasmid was 1 x 10(3) and the concentration of oncogenic 1 x 10(2). Validation of MAMA primers in in vivo samples demonstrated that oncogenic primers can be used for both early diagnosis of MD in feather pulp (FP) samples collected at 3 wk of age and confirmation of MD diagnosis in tumors. CVI988 primers could be used to monitor CVI988 vaccination in samples with a low load of oncogenic MDV DNA (latently infected samples or negative) but not in samples with a high load of oncogenic MDV DNA (tumors). Our results suggest that monitoring CVI988 vaccination in FP samples collected at 1 wk of age ensures the specificity of the CVI988 primers. PMID:25055627

  4. [Wilson disease in 2003].

    PubMed

    Szalay, Ferenc

    2003-12-14

    The actuality of this review is based on the results of a recent international consensus conference on the diagnosis and phenotypic classification of Wilson disease published in 2003. The mechanism of the genetically determined copper elimination failure and the copper toxicity, the clinical presentation forms, the diagnosis and treatment of the disease is reviewed. Wilson disease should be taken into consideration in case of any liver disease of unknown origin or neuropsychiatric symptoms. The internationally accepted scoring system is presented. PMID:15067983

  5. Rice Diseases Atlas. 

    E-print Network

    Walla, Walter

    1977-01-01

    . This condition is common early in the growing season when soil temperatures are cool FOLIAGE DISEASES Rice Blast - (fungus Piricularia oryzae) - Blast is one of the most important rice diseases in Texas. This disease varies in severity from year to year.... ~ ______________________________________________________________________ 5 Brown Leaf Sppt - (fungus He/minthosporium oryzae) - The disease is found on leaves, leaf sheath, panicle branches, glumes and grain. The fungus causes brown circular to oval spots on the first leaf sheath while it is still below ground...

  6. Telomeres in disease

    PubMed Central

    Calado, Rodrigo

    2012-01-01

    Telomeres and telomere repair are basic molecular features of cells possessing linear DNA chromosomes and defects in them result in various diseases. This review examines recent advances in understanding these diseases, particularly at a molecular level, and in relating telomere dysfunction to clinical diseases. We also discuss the potential role of telomere elongation as a therapy in diseases, and more controversially, the prevention/reversal of aging. PMID:22500192

  7. Parallelization: Infectious Disease

    NSDL National Science Digital Library

    Aaron Weeden

    Epidemiology is the study of infectious disease. Infectious diseases are said to be "contagious" among people if they are transmittable from one person to another. Epidemiologists can use models to assist them in predicting the behavior of infectious diseases. This module will develop a simple agent-based infectious disease model, develop a parallel algorithm based on the model, provide a coded implementation for the algorithm, and explore the scaling of the coded implementation on high performance cluster resources.

  8. Meningococcal Disease: Surveillance

    MedlinePLUS

    ... Meningococcal Vaccination Surveillance Meningococcal Outbreaks About Meningococcal Outbreaks Serogroup B Meningococcal Vaccine & Outbreaks Clinical Information Laboratory Information Meningococcal Disease in ...

  9. Meningococcal Disease: Risk Factors

    MedlinePLUS

    ... Meningococcal Vaccination Surveillance Meningococcal Outbreaks About Meningococcal Outbreaks Serogroup B Meningococcal Vaccine & Outbreaks Clinical Information Laboratory Information Meningococcal Disease in ...

  10. Paget's Disease of Bone

    MedlinePLUS

    ... break easily. The disease can lead to other health problems, too, such as arthritis and hearing loss. You can have Paget's disease in any bone, but it is most common in the spine, pelvis, skull, and legs. The disease might affect ...

  11. Newcastle disease virus (velogens)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Newcastle disease virus (NDV) is also known as avian paramyxovirus serotype-1 (APMV-1). While all NDV are referred to as APMV-1 and are of one serotype, only infections with virulent NDV (vNDV) cause Newcastle disease (ND). Newcastle disease virus strains are defined as virulent if they 1) have th...

  12. Newcastle disease vaccines

    Microsoft Academic Search

    Gilad E. Gallili; David Ben-Nathan

    1998-01-01

    Newcastle disease (ND) is a worldwide problem with severe economic implications, affecting chickens, turkeys and other birds. Newcastle disease virus (NDV), a member of the Paramyxoviridae group can cause disease of diverse severity in accordance with environmental factors. NDV strains are classified according to their virulence into three categories. The lentogenic strains are very mild and naturally inhabit healthy flocks.

  13. Smoking and Parkinson's disease

    Microsoft Academic Search

    R B Godwin-Austen; P N Lee; M G Marmot; G M Stern

    1982-01-01

    In a case control study of the relationship between smoking habits and Parkinson's disease a negative association was demonstrated with a relative risk of 0 x 52. A history of smoking up to 20 years earlier was associated with a risk of developing Parkinson's disease equal to about half that in non-smokers. The type of disease, age of onset and

  14. Alzheimers disease Neurodegeneration

    E-print Network

    Schüler, Axel

    Keywords Alzheimer´s disease Neurodegeneration Cell cycle and apoptosis » Prof. Dr. Thomas Arendt The research group is working on the pathomechanism of Alzheimer´s disease and related of the cholinergic ba- sal forebrain system in Alzheimer´s disease which provides the basis for the currently

  15. Management of Cushing disease

    Microsoft Academic Search

    Beverly M. K. Biller; Brooke Swearingen; Nicholas A. Tritos

    2011-01-01

    Cushing disease is caused by a corticotroph tumor of the pituitary gland. Patients with Cushing disease are usually treated with transsphenoidal surgery, as this approach leads to remission in 70–90% of cases and is associated with low morbidity when performed by experienced pituitary gland surgeons. Nonetheless, among patients in postoperative remission, the risk of recurrence of Cushing disease could reach

  16. Molecular Bioinformatics for Diseases

    E-print Network

    Radivojac, Predrag

    . Curr Opin Pediatr, 13: 22 (2001). Leads to sickle cell anemia Manifestation of disease vastly different. PNAS, 104: 8685 (2007). #12;Mendelian diseases E6V6 Sickle Cell Disease: Autosomal recessive disorder 4 of amyloid fibrils Abnormally shaped red blood cells Pauling et al. Science 110: 543 (1949). Chui & Dover

  17. Infections and autoimmune diseases

    Microsoft Academic Search

    Jean-François Bach

    2005-01-01

    The high percentage of disease-discordant pairs of monozygotic twins demonstrates the central role of environmental factors in the etiology of autoimmune diseases. Efforts were first focussed on the search for triggering factors. The study of animal models has clearly shown that infections may trigger autoimmune diseases, as in the case of Coxsackie B4 virus in type I diabetes and the

  18. Deer: Wasting Disease Disaster.

    NSDL National Science Digital Library

    2002-01-01

    Chronic wasting disease, the brain disease sometimes compared to mad cow disease that affects deer and elk, has become a problem outside of the states of Colorado and Wyoming where it has been known for decades, raising awareness and concern for wildlife in affected areas. This Web site is a recent Why Files discussing the epidemic and Wisconsin's plans to control it.

  19. Heart Disease in Women

    MedlinePLUS

    ... United States, 1 in 4 women dies from heart disease. The most common cause of heart disease in both men and women is narrowing ... the blood vessels that supply blood to the heart itself. This is called coronary artery disease, and ...

  20. Venereal Disease. Second Edition.

    ERIC Educational Resources Information Center

    Bender, Stephen J.

    This book is one in a series of contemporary topics in health science for students. The first chapter deals with the behavioral aspects of venereal disease and how the disease has been affected by our changing society. Chapter 2 discusses the magnitude of the problem, presenting various maps and charts. The history of venereal disease and the…

  1. Disease and their management.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter reviews diseases of chickpea and their management practices. Some of the most important disease such as Ascochyta blight, Fuarium wilt, Botrytis gray mold, are described in detail. The life cycle and epidemiology of these diseases are discussed in relation to the management practices. ...

  2. Secondary minimal change disease

    Microsoft Academic Search

    Richard J. Glassock

    2003-01-01

    The great majority of patients identified as having a 'minimal change lesion' accompanying the nephrotic syndrome have a primary or 'idiopathic' disorder. Nevertheless, it is quite apparent that a similar or identical lesion can appear consequent to a growing number of underlying diseases; it is then known as 'secondary minimal change disease'. The predisposing conditions include neoplastic diseases, toxic or

  3. Enteric Redmouth Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Yersinia ruckeri, the causative agent of Enteric Redmouth Disease (ERM), is a disease of salmonid fish species that is endemic in areas of the world where salmonids are intensively cultured. The disease causes a chronic to acute hemorrhagic septicemia which can lead to high rates of mortality partic...

  4. Celiac Disease: Internet Resources

    Microsoft Academic Search

    Brian D. Cameron

    2002-01-01

    Celiac disease is an autoimmune malabsorption disorder caused by gluten, the protein present in wheat, rye, and barley. Gluten destroys the absorptive layer of the small intestine, which leads to malnourishment and other serious diseases. Recent research has established that celiac disease is a common disorder, affecting 1 in every 120 to 300 people in North America and Europe. The

  5. Primary glomerular disease

    Microsoft Academic Search

    Peter Mathieson

    2011-01-01

    This article reviews the clinical features, pathogenesis, investigation and management of glomerulonephritis (GN). This can occur as a primary isolated renal disease, as a manifestation of systemic diseases such as vasculitis or lupus, or secondary to drugs, infections or tumours. It is an important cause of morbidity and mortality and a potentially preventable cause of end-stage renal disease, so early

  6. Primary glomerular disease

    Microsoft Academic Search

    Momir Macanovic; Peter Mathieson

    2007-01-01

    This article reviews the clinical features, pathogenesis, investigation and management of glomerulonephritis (GN). This can occur as a primary isolated renal disease, as a manifestation of systemic diseases such as vasculitis or lupus, or secondary to drugs, infections or tumours. It is an important cause of morbidity and mortality and a potentially preventable cause of end-stage renal disease, so early

  7. Gaucher's disease and pregnancy.

    PubMed

    Moughabghab, A V; Fenides, A; Hanon, F; Socolovsky, C

    1994-01-01

    For a long time, pregnancy has been discouraged for patients with Gaucher's disease. Because of the scarcity of complications found in the literature, the obstetrical attitude is favorable towards an authorization of pregnancy for patients with Gaucher's disease. We describe the evolution of pregnancy of a woman suffering from Gaucher's disease type I and the anesthesiological support provided. PMID:7847042

  8. Anosognosia in neurodegenerative disease

    Microsoft Academic Search

    Howard J. Rosen

    2011-01-01

    Patients with neurological disorders are often partially or completely unaware of the deficits caused by their disease. This impairment is referred to as anosognosia, and it is very common in neurodegenerative disease, particularly in frontotemporal dementia. Anosognosia has significant impacts on function and quality of life for patients with neurodegenerative disease and their caregivers, but the phenomenon has received little

  9. Skin Diseases: Skin Health and Skin Diseases

    MedlinePLUS

    ... color or outline, or in any other way. Psoriasis © 2008 Logical Images, Inc. Psoriasis —A skin disease that causes scaling and swelling. Most psoriasis causes patches of thick, red skin with silvery ...

  10. Cardiovascular Disease (CVD) Coronary heart disease

    E-print Network

    Dever, Jennifer A.

    have a greater prevalence in women · Osteoporosis · Autoimmune disease A. Osteoporosis · Osteoporosis ­ disorder of low bone mass, microarchitectural denegra7on% of all women >65 years old have osteoporosis (15% of all Caucasian women

  11. HIV and Cardiovascular Disease (Heart Disease)

    MedlinePLUS Videos and Cool Tools

    ... signal problems with the reabsorption in the tubules. Diabetes Recent studies about diabetes risks for those with HIV contain some conflicting ... it is clear that minimizing your risks for diabetes is important. Diabetes contributes to heart disease and ...

  12. Creutzfeldt--Jakob disease.

    PubMed Central

    Matthews, W. B.

    1978-01-01

    The laboratory transmission to animals of an apparently degenerative disease of the nervous system, Creutzfeldt-Jakob disease (CJD), is now well established. Important questions arising from this observation are the possibility of natural transmission or infectivity and the existence of other similarly transmissible diseases. Epidemiological studies have revealed some possible clusters of CJD and also an association with previous craniotomy, but there is no definite evidence of natural infection. A few instances have been reported of experimental CJD in animals following inoculation with material from Alzheimer's disease, but apart from this there is so far no evidence of transmission of any other form of degenerative nervous disease. PMID:103082

  13. Lyme disease in athletes.

    PubMed

    DuPrey, Kevin M

    2015-01-01

    Lyme disease, a bacterial infection transmitted by ticks, is the most common vector-borne disease in the northern hemisphere. Athletes who train or compete in wooded environments in endemic regions are at increased risk of contracting Lyme disease. Variability in clinical presentation, masquerading symptoms, and limitations in testing may lead to misdiagnosis. Early diagnosis and treatment result in full recovery for most patients with Lyme disease; however symptoms may persist for months to years, especially when diagnosis is delayed. This article reviews the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of Lyme disease, with focus on the athletic population. PMID:25574885

  14. Behçet's disease as a systemic disease.

    PubMed

    Mat, M Cem; Sevim, Ay?egül; Fresko, Izzet; Tüzün, Yalç?n

    2014-01-01

    Behçet's disease usually begins with cutaneous manifestations, such as recurrent aphthous stomatitis, genital ulcers, erythema nodosum-like lesions, papulopustular findings, and pathergy phenomenon. Recurrent aphthous stomatitis is generally the first sign, and other findings may develop in the course of the disease. There is no specific diagnostic available for Behçet's disease. It is most prevalent among patients along the ancient Silk Road. The high frequency of HLA-B51 among a wide range of ethnic populations favors the role of genetic factors. Behçet's disease usually appears in the third to fourth decade of life, and is rarely seen in children and adults over 50 years of age. It affects both genders equally, but the course of the disease is more severe in men. Eye involvement leading to loss of vision, plus vascular, articular, and central nervous system involvement are more commonly observed among men. Behçet's disease is a systemic inflammatory disorder. A complex genetic background, coupled with innate and adaptive immune system activation, causes the diverse clinical manifestations that characterize the clinical picture. PMID:24767193

  15. Structural imaging biomarkers of Alzheimer's disease: predicting disease progression

    E-print Network

    Paris-Sud XI, Université de

    1 Structural imaging biomarkers of Alzheimer's disease: predicting disease the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www of Alzheimer's disease (AD) may allow earlier detection and refined pre- diction

  16. Prioritising Infectious Disease Mapping

    PubMed Central

    Pigott, David M.; Howes, Rosalind E.; Wiebe, Antoinette; Battle, Katherine E.; Golding, Nick; Gething, Peter W.; Dowell, Scott F.; Farag, Tamer H.; Garcia, Andres J.; Kimball, Ann M.; Krause, L. Kendall; Smith, Craig H.; Brooker, Simon J.; Kyu, Hmwe H.; Vos, Theo; Murray, Christopher J. L.; Moyes, Catherine L.; Hay, Simon I.

    2015-01-01

    Background Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease (ID) mapping for public health uses. Whilst a large number of IDs show global spatial variation, comprehensive knowledge of these geographic patterns is poor. Here we use an objective method to prioritise mapping efforts to begin to address the large deficit in global disease maps currently available. Methodology/Principal Findings Automation of ID mapping requires bespoke methodological adjustments tailored to the epidemiological characteristics of different types of diseases. Diseases were therefore grouped into 33 clusters based upon taxonomic divisions and shared epidemiological characteristics. Disability-adjusted life years, derived from the Global Burden of Disease 2013 study, were used as a globally consistent metric of disease burden. A review of global health stakeholders, existing literature and national health priorities was undertaken to assess relative interest in the diseases. The clusters were ranked by combining both metrics, which identified 44 diseases of main concern within 15 principle clusters. Whilst malaria, HIV and tuberculosis were the highest priority due to their considerable burden, the high priority clusters were dominated by neglected tropical diseases and vector-borne parasites. Conclusions/Significance A quantitative, easily-updated and flexible framework for prioritising diseases is presented here. The study identifies a possible future strategy for those diseases where significant knowledge gaps remain, as well as recognising those where global mapping programs have already made significant progress. For many conditions, potential shared epidemiological information has yet to be exploited. PMID:26061527

  17. Fight against infectious diseases.

    PubMed

    Soda, K; Kamakura, M; Kitamura, K

    1996-08-01

    During early Meiji era in Japan, there were frequent epidemics of fatal acute communicable diseases such as cholera, dysentery and smallpox, and preventive measures and preparations for acute infectious diseases were urgently needed. Together with improvement of scientific preparations, the Communicable Disease Prevention Law was promulgated in 1897. Then gradually until 1940's, the focus of preventive measures have been shifted from acute infectious diseases to chronic ones, particularly tuberculosis. After the World War II, except the short period of social confusion, major legally-defined communicable diseases had been decreasing rapidly mainly due to the use of antibiotics and improvement of environmental sanitation. At the same time, the introduction of preventive vaccination marked a new era for the prevention of infectious diseases and was largely responsible for the remarkable decrease of infant mortality in Japan. Recently the concept of defense by vaccination against infectious diseases has evolved from group-oriented to individual-oriented, so that the Preventive Vaccination Law was drastically revised in 1994. Currently, effective counter-measures against newly emerged infectious diseases, as viral hepatitis, institution-acquired infection, viral hemorrhagic fever etc., have been implemented. For the future, improvement of infections disease surveillance, vaccine development and expansion of vaccination coverage along with monitoring side-effects, preventive health education on AIDS/STDs, addressing the special needs of foreigners living in Japan and international collaboration for disease control abroad are all vital to the success of protection of the public's health from infectious diseases in Japan. PMID:8800275

  18. [Tinnitus in systemic diseases].

    PubMed

    Nowak, Katarzyna; Banaszewski, Jacek; Dabrowski, Piotr; Szymiec, Eugeniusz; Szyfter, Witold

    2002-01-01

    Permanent or temporary degenerative changes in the internal ear causing tinnitus may occur with particular intensity in patients suffering from systemic disease (diabetes, hypertension, rheumatic diseases, kidney and thyroid gland diseases). Pathomechanisms of hearing impairment and the risk of tinnitus and its character in particular cases are discussed in the paper. The research was carried out on 1200 patients treated in the Laryngological Rehabilitation Centre in Pozna? between 1.1.1998 and 04.2001 due to tinnitus. The analysis included the diagnosis of general health condition, general laryngological examination as well as additional tests. In the examined group 34% suffered from systemic diseases. Among them the highest percentage (47%) suffered from hypertension, 41% from hypercholesterolaemia, 22% from rheumatic diseases and 16% from diabetes. 96% of the patients had a long family history of diseases. The additional factor causing damage of the internal ear may be ototoxic drug used in the treatment of many systemic diseases. PMID:12094648

  19. Belatacept-Based Immunosuppression in De Novo Liver Transplant Recipients: 1-Year Experience From a Phase II Randomized Study

    PubMed Central

    Klintmalm, G B; Feng, S; Lake, J R; Vargas, H E; Wekerle, T; Agnes, S; Brown, K A; Nashan, B; Rostaing, L; Meadows-Shropshire, S; Agarwal, M; Harler, M B; García-Valdecasas, J-C

    2014-01-01

    This exploratory phase II study evaluated the safety and efficacy of belatacept in de novo adult liver transplant recipients. Patients were randomized (N = 260) to one of the following immunosuppressive regimens: (i) basiliximab + belatacept high dose [HD] + mycophenolate mofetil (MMF), (ii) belatacept HD + MMF, (iii) belatacept low dose [LD] + MMF, (iv) tacrolimus + MMF, or (v) tacrolimus alone. All received corticosteroids. Demographic characteristics were similar among groups. The proportion of patients who met the primary end point (composite of acute rejection, graft loss, death by month 6) was higher in the belatacept groups (42–48%) versus tacrolimus groups (15–38%), with the highest number of deaths and grafts losses in the belatacept LD group. By month 12, the proportion surviving with a functioning graft was higher with tacrolimus + MMF (93%) and lower with belatacept LD (67%) versus other groups (90%: basiliximab + belatacept HD; 83%: belatacept HD; 88%: tacrolimus). Mean calculated GFR was 15–34 mL/min higher in belatacept-treated patients at 1 year. Two cases of posttransplant lymphoproliferative disease and one case of progressive multifocal leukoencephalopathy occurred in belatacept-treated patients. Follow-up beyond month 12 revealed an increase in death and graft loss in another belatacept group (belatacept HD), after which the study was terminated. PMID:25041339

  20. Post-transplantation primary central nervous system lymphoma in a patient with systemic lupus erythematosus and prolonged use of immunosuppressant.

    PubMed

    Tse, Teresa P K; Chan, Allan N L; Chan, Tony K T; Po, Y C

    2014-12-01

    Post-transplantation primary central nervous system lymphoma is an uncommon and fatal post-transplant lymphoproliferative disorder. Such lymphomas have been described in only a few case series in the literature. The incidence of this condition is rising with improved survival after organ transplantation. A case of post-transplantation primary central nervous system lymphoma in a young Chinese woman with systemic lupus erythematosus is described here. She presented with right-sided weakness and memory loss after tooth extraction 2 weeks before admission. Contrast computed tomography of the brain demonstrated a contrast rim-enhancing lesion over the left frontal lobe. With a history of recent dental procedure, long-term immunosuppressive therapy and computed tomography findings, cerebral abscess was highly suspected. Emergency operation was performed. Histopathology showed post-transplantation primary central nervous system lymphoma, with cells positive for B-cell marker CD20. Immunosuppressant was stopped and she was treated with radiotherapy and rituximab (anti-CD20 monoclonal antibody). She remained disease-free at 16 months. Post-transplantation primary central nervous system lymphoma is rare with variable presentation and radiological features. We believe rituximab may have a role in the treatment of such lymphomas. PMID:25488034