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Sample records for lymphoproliferative disorder multiple

  1. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    Science.gov (United States)

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD.

  2. Multiple clinical presentations of lymphoproliferative disorders in pediatric liver transplant recipients: a single-center experience.

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

    2010-06-01

    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%). The age at diagnosis ranged from 12 to 258 months (median, 47), and the time from transplantation ranged from 1 to 84 months (median, 13). Ten of these children (76.9%) were EBV-naïve prior to transplantation. Fever was present in all cases. The clinical signs at presentation were anemia (92.3%), diarrhea and vomiting (69.2%), recurrent upper airway infections (38.4%), Waldeyer ring lymphoid tissue hypertrophy (23.0%), abdominal mass lesions (30.7%), massive cervical and mediastinal adenopathy (15.3%), or gastrointestinal and respiratory symptoms (30.7%). One child developed fulminant hepatic allograft failure secondary to graft involvement by PTLD. Polymorphic PTLD was diagnosed in 6 patients; 7 had the diagnosis of lymphoma. Treatment consisted of stopping immunosuppression as well as starting intravenous gancyclovir and anti-CD20 monoclonal antibody therapy. The mortality rate was 53.8%. The clinical presentation of PTLD varied from fever of unknown origin to fulminant hepatic failure. The other symptoms that may be linked to the diagnosis of PTLD are pancytopenia, tonsil and adenoid hypertrophy, cervical or mediastinal lymph node enlargement, as well as abdominal masses. Despite numerous advances, the optimal treatment approach for PTLD is not completely known and the mortality rate is still high.

  3. Mutlifocal osseous posttransplantation lymphoproliferative disorder: case report

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    Lo, Ryan [University of Chicago, Department of Radiology, Chicago, IL (United States); Michalicek, Zachary [Northshore University Healthsystems, Department of Pathology, Evanston, IL (United States); Lazarus, Martin [Northshore University Healthsystems, Department of Radiology, Evanston, IL (United States)

    2015-02-14

    Posttransplant lymphoproliferative disorder (PTLD) is a known complication of organ transplantation, but musculoskeletal involvement of PTLD remains very rare. We present a case of recurrent PTLD of the bone in a heart transplant patient that was misdiagnosed as gout for several years. There are only a few cases of osseous PTLD in the literature, and we hope to better characterize its imaging findings on multiple imaging modalities. (orig.)

  4. Autoimmune lymphoproliferative disorder in an adult patient

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    N K Desai

    2011-01-01

    Full Text Available A 50-year-old male patient presented with fever, epistaxis and multiple lymphadenopathy since 15 days. In the light of the above presentation a complete workup was initiated to exclude common conditions like tuberculosis, acquired immunodeficiency syndrome, lymphoid malignancy and sarcoidosis. After excluding common conditions a biopsy of cervical lymph node demonstrated reactive lymphadenitis with paracortical hyperplasia. Immunohistochemistry demonstrated double negative lymphocytes (CD4-, CD8-. A diagnosis of autoimmune lymphoproliferative disorder syndrome (ALPS (probable was made and patient was started on 1 mg/kg of steroids. Patient showed a dramatic improvement with respect to general wellbeing, fever and regression of lymphadenopathy. This entity of ALPS has been recently identified and classified; most of the reports are from the pediatric population. To the best of our knowledge ours is one of the few cases of this entity being reported in an adult patient from India.

  5. Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

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    Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su [Dept. of Radiology, Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2012-04-15

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

  6. Isolated Upper Extremity Posttransplant Lymphoproliferative Disorder in a Child

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    Sarah E. Halula

    2015-01-01

    Full Text Available 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.

  7. Posttransplant lymphoproliferative disorder in pediatric liver transplantation.

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    Uribe, M; Hunter, B; Alba, A; Calabrán, L; Flores, L; Soto, P; Herzog, C

    2009-01-01

    The success rate of pediatric liver transplantation has improved in recent years. Advances in immunosuppression have reduced the risk of rejection, but have enhanced the risk of posttransplant lymphoproliferative disorder (PTLD). Since 1994, we have performed 197 orthotopic liver transplantations in 157 recipients younger than 15 years. Herein we have performed a retrospective study to review the incidence and clinical characteristics, along with the treatment and outcomes of PTLD diagnosed over this 14-year experience. We documented 8 cases of PTLD (5%), half of which occurred during the first 2 years posttransplantation; 5 presented with abdominal involvement and 2 with thoracic masses. The histological findings showed lymphoma in 6 cases. All were treated with reduction of immunosuppression and 2 received Rituximab. Three patients died, a mortality rate of 37.5%. One subject experienced rejection, and the others responded to treatment. PTLD is a life-threatening condition that requires a high index of suspicion, appropriate imaging, biopsy diagnosis, and prompt treatment to achieve positive results. Quantitative monitoring of Epstein-Barr virus load may be useful to detect a high-risk population.

  8. A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder

    Science.gov (United States)

    Smith, Casey; Streicher, Andrew; Magnuson, Allison; Newman, Susan; Bertoli, Robert

    2017-01-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation. A 69-year-old Asian male, who underwent postrenal transplant nine years earlier, presented with a one-month history of new onset seizure activity. His evaluation revealed multiple brain lesions on magnetic resonance imaging (MRI), as well as serologic and cerebrospinal fluid studies which were positive for Epstein-Barr Virus (EBV) infection. Ultimately, he underwent craniotomy with tissue biopsy with the final pathology report showing posttransplant lymphoproliferative disorder, polymorphic type. The patient was managed with reduction in immunosuppression, rituximab therapy, and cranial radiation treatments. He had demonstrated marked improvement in his neurologic function and was ultimately discharged to inpatient rehabilitation facility. PMID:28116196

  9. MicroRNA gene expression in malignant lymphoproliferative disorders

    Institute of Scientific and Technical Information of China (English)

    XU Wei; LI Jian-yong

    2007-01-01

    Objective To review the recent studies about microRNAs and advances in malignant lymphoproliferative disorders.Data sources Published articles (2001-2006) about microRNAs and malignant iymphoproliferative disorders were selected using MEDLINE.Study selection After independent review by two observers, 43 of 421 originally identified articles were selected that specifically addressed the stated purpose.Results Two observers independently assessed studies using explicit methodological criteria for evaluating microRNAs in malignant lymphoproliferative disorders. Recent work has revealed a class of small noncoding RNA species,microRNAs, which affect various biological processes. MicroRNAs inhibit the expression of protein encoding genes at the posttranscriptional level in a variety of eukaryotic organisms. In this review, we focused on the biogenetic pathways of microRNAs (miR-15a, miR-16-1, miR-155, miR-17-92 cluster, miR-142) and discussed the implications for human malignant lymphoproliferative disorders.Conclusions microRNAs are involved in tumorigenesis and mediate gene regulation as a fundamental genetic program at the posttranscriptional level. Further study of microRNAs may lead to novel concepts in the diagnosis and treatment of malignant lymphoproliferative disorders.

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

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    Efthymia Vlachaki

    2012-01-01

    Full Text Available 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.

  11. Pure red cell aplasia and lymphoproliferative disorders: an infrequent association.

    Science.gov (United States)

    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.

  12. Hepatitis C virus-related lymphoproliferative disorders: An overview

    Institute of Scientific and Technical Information of China (English)

    Anna Linda Zignego; Carlo Giannini; Clodoveo Ferri

    2007-01-01

    Hepatitis C virus (HCV) is a global health problem affecting 3% of the world's population (about 180 million) and a cause of both hepatic and extrahepatic diseases. B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia, represent the most closely related as well as the most investigated HCV-related extrahepatic disorder. The association between extrahepatic (lymphoma) as well as hepatic malignancies (hepatocellular carcinoma) has justified the inclusion of HCV among human cancer viruses. HCV-associated manifestations also include porphyria cutanea tarda,lichen planus, nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis, diabetes,chronic polyarthritis, sexual dysfunctions, cardiopathy/atherosclerosis, and psychopathological disorders.A pathogenetic link between HCV virus and some lymphoproliferative disorders was confirmed by their responsiveness to antiviral therapy, which is now considered the first choice treatment. The aim of the present paper is to provide an overview of extrahepatic manifestations of HCV infection with particular attention to B-cell lymphoproliferative disorders. Available pathogenetic hypotheses and suggestions about the most appropriate, currently available, therapeutic approaches will also be discussed.

  13. Thymic Hyperplasia after Lung Transplantation Imitating Posttransplant Lymphoproliferative Disorder

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    Christina Maria Steger

    2011-01-01

    Full Text Available Thymic hyperplasia is usually associated with the treatment of malignant tumours and is sometimes linked with endocrine diseases. For the first time, we report a case of thymic hyperplasia in a patient 2 years after bilateral lung transplantation. Contrast-enhanced chest CT scan was highly suspicious for a posttransplant lymphoma or thymoma. Therefore, the patient received total thymectomy. Excised specimens were sent to the Department of Pathology. Unexpectedly, the histological examination revealed hyperplastic thymic tissue without evidence for a posttransplant lymphoproliferative disorder or malignancy.

  14. Post-transplant lymphoproliferative disorders of oral cavity.

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    Ojha, Junu; Islam, Nadim; Cohen, Donald M; Marshal, David; Reavis, Michael R; Bhattacharyya, Indraneel

    2008-05-01

    Post-transplant lymphoproliferative disorders (PTLD) are long-term complications of immunosuppression after solid organ/bone marrow transplantation. In most cases, PTLD arises as a result of primary or reactivated Epstein-Barr virus infection in a host with impaired cellular immunity. PTLD is most often seen in the gastrointestinal tract, although it has also been reported in other organ systems, including the central nervous system and, rarely, in the head and neck. It is characterized histologically by abnormal lymphoid cell proliferation. Although many forms of PTLD do not meet all of the histologic criteria of lymphoma, they often behave clinically in a malignant fashion if left untreated. We present 3 rare cases of PTLD manifesting in the oral cavity as mucosal masses after solid organ transplantation. There are only 8 published reports of PTLD in the literature presenting as oral lesions. The clinical, pathologic, and therapeutic spectra of PTLD are discussed.

  15. Interleukin-10 and posttransplant lymphoproliferative disorder after kidney transplantation

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Bendtzen, K.; Moller, B.;

    1999-01-01

    Background. Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation, which comprises a morphologically and clinically heterogeneous spectrum of B-lymphocyte diseases. Risk factors include primary or reactivated Epstein-Barr virus (EBV) infection...... to the development of PTLD in three kidney transplanted patients. The study now includes nine patients that could be followed before and/or after the occurrence of lymphoma, Methods. Nine patients with lymphomas (eight PTLDs and one Hodgkin's disease) were diagnosed among 268 consecutive renal transplantations (1990...... human recombinant IL-10 was employed; the assay is specific for human natural and viral IL-10, Results, Three patients experienced primary EBV infection, five reactivated EBV infections, and one did not change EBV status. Three patients had a fulminant course and died with EBV-associated PTLD; confirmed...

  16. Notch signalling in primary cutaneous CD30+ lymphoproliferative disorders: a new therapeutic approach?

    DEFF Research Database (Denmark)

    Kamstrup, M R; Biskup, E; Gniadecki, R

    2010-01-01

    The oncogenic potential of deregulated Notch signalling has been described in several haematopoietic malignancies. We have previously reported an increased expression of Notch1 in primary cutaneous CD30+ lymphoproliferative disorders, lymphomatoid papulosis and primary cutaneous anaplastic large-...

  17. Notch signalling in primary cutaneous CD30+ lymphoproliferative disorders: a new therapeutic approach?

    DEFF Research Database (Denmark)

    Kamstrup, M R; Biskup, E; Gniadecki, R

    2010-01-01

    The oncogenic potential of deregulated Notch signalling has been described in several haematopoietic malignancies. We have previously reported an increased expression of Notch1 in primary cutaneous CD30+ lymphoproliferative disorders, lymphomatoid papulosis and primary cutaneous anaplastic large...

  18. Gastrointestinal involvement of posttransplant lymphoproliferative disorder in lung transplant recipients: report of a case.

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    Shitrit, David; Shitrit, Ariella Bar-Gil; Dickman, Ram; Sahar, Gidon; Saute, Milton; Kramer, Mordechai R

    2005-11-01

    Lymphoproliferative disorder is a well-recognized complication of lung transplantation. Risk factors include Epstein-Barr virus infection and immunosuppression. The gastrointestinal manifestations of post-transplant lymphoproliferative disorder in lung transplant recipients have not been fully characterized. Case presentation and 16 previously reported cases of post-transplant lymphoproliferative disorder with gastrointestinal involvement are reviewed. Patient ages ranged from 25 to 65 (median, 52) years. Median time from lung transplantation to onset of posttransplant lymphoproliferative disorder was 36 (range, 1-109) months; 35 percent of cases (6/17) occurred within 18 months; Eighty-eight percent of patients (15/17) had positive Epstein-Barr virus serology before transplantation. In five patients (29 percent), the posttransplant lymphoproliferative disorder also involved sites other than the gastrointestinal tract. The most common gastrointestinal site of posttransplant lymphoproliferative disorder was the colon, followed by the small intestine and stomach. Clinical features included abdominal pain, nausea, and bloody diarrhea. Diagnosis was based on typical pathologic changes on gastrointestinal tract biopsy obtained mainly by colonoscopy. Treatment included a reduction in the immunosuppressive regimen in 15 of 17 cases (88 percent) and surgical resection in 10 (59 percent). One patient was untreated. Seven of 16 patients (44 percent) responded to treatment and 9 patients died. Median time from onset of posttransplant lymphoproliferative disorder to death was 70 (range, 10-85) days. Posttransplant lymphoproliferative disorder with gastrointestinal involvement is a unique entity that should be considered in all Epstein-Barr-Virus-positive lung transplant recipients who present with abdominal symptoms. Although immunosuppressive modulation and resection can lead to remission, the risk of death is 50 percent.

  19. Ibrutinib: another weapon in our arsenal against lympho-proliferative disorders.

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    Cabras, Maria Giuseppina; Angelucci, Emanuele

    2015-01-01

    In Volume 16, issue 12 of Expert Opinion on Pharmacotherapy, an important article on the new drug ibrutinib was published. This new drug promises to further improve outcome in the treatment of several lympho-proliferative disorders. In this editorial, the most important findings of the article looking particularly to the integration of ibrutinib in current clinical practice will be summarized. Finally this editorial will focus on the next challenges for scientists and physicians in the treatment of lympho-proliferative disorders.

  20. Human immunodeficiency virus (HIV)-associated polymorphic lymphoproliferative disorders.

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    Nador, Roland G; Chadburn, Amy; Gundappa, Girija; Cesarman, Ethel; Said, Jonathan W; Knowles, Daniel M

    2003-03-01

    The majority of AIDS-related non-Hodgkin's lymphomas are clinically aggressive monoclonal B-cell Burkitt's lymphomas, large cell lymphomas, or immunoblastic lymphomas. In contrast, the lymphoid proliferations arising in solid organ transplant recipients, collectively referred to as posttransplantation lymphoproliferative disorders (PT-LPDs), represent a clinically and histopathologically heterogeneous group of Epstein-Barr virus (EBV)-driven B-cell proliferations of variable clonal composition. During a retrospective histopathologic review of lymphoid proliferations associated with human immunodeficiency virus (HIV) infection we identified 10 cases that morphologically resemble the polymorphic PT-LPDs. They arose in lymph nodes (five), lungs (two), and the parotid gland, perineum, and skin (one each). They exhibit a diffuse growth pattern and are composed of a polymorphic lymphoid cell population exhibiting a variable degree of plasmacytic differentiation, cytologic atypia, and numbers of atypical immunoblasts. A clonal B-cell population was detected by immunoglobulin heavy and light chain gene rearrangement and/or EBV terminal repeat analysis in 8 of the 10 (80%) cases by Southern blotting. The nongermline hybridizing bands were usually faint, however, suggesting that the clonal B-cell population represented only a subpopulation within the polymorphic lesion. Strong clonal rearrangement bands were present in one case in which there was clear morphologic evidence of transformation to diffuse large cell lymphoma. This case exhibited C-MYC, BCL-6, and p53 gene mutations. One other case exhibited a p53 gene mutation. The remaining eight cases lacked C-MYC, BCL-6, RAS, and p53 gene alterations. Clonal EBV infection was detected in 4 of the 10 (40%) lesions. Like EBV-containing PT-LPDs, all four EBV-positive HIV-associated polymorphic lesions were associated with type A EBV. The Kaposi's sarcoma-associated herpesvirus was detectable in two cases by polymerase chain

  1. The accuracy of positron emission tomography in the detection of posttransplant lymphoproliferative disorder.

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    Dierickx, Daan; Tousseyn, Thomas; Requilé, Annelies; Verscuren, Raf; Sagaert, Xavier; Morscio, Julie; Wlodarska, Iwona; Herreman, An; Kuypers, Dirk; Van Cleemput, Johan; Nevens, Frederik; Dupont, Lieven; Uyttebroeck, Anne; Pirenne, Jacques; De Wolf-Peeters, Christiane; Verhoef, Gregor; Brepoels, Lieselot; Gheysens, Olivier

    2013-05-01

    We investigated sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-fluorodeoxyglucose-positron emission tomography in 170 cases with suspected or biopsy-proven posttransplant lymphoproliferative disorder. All solid organ and hematopoietic stem cell transplant recipients who underwent an 18F-fluorodeoxyglucose-positron emission tomography scan between 2003 and 2010 in our center for the indication posttransplant lymphoproliferative disorder, were retrospectively reviewed and results were compared with tissue biopsy whenever possible. One hundred and seventy positron emission tomography scans in 150 patients were eligible for evaluation. In 45 cases, the patient had a biopsy-confirmed posttransplant lymphoproliferative disorder before positron emission tomography scanning and positron emission tomography was performed for staging purposes. In the remaining 125 cases, positron emission tomography was performed to differentiate between posttransplant lymphoproliferative disorder and other diseases. 18F-fluorodeoxyglucose-uptake was quantitatively expressed by calculation of maximum and mean standardized uptake value in the most intense lesion or, in the absence of attenuation corrected positron emission tomography scans, by comparing uptake in target lesion to liver and mediastinal uptake. We found an overall sensitivity of 89%, specificity of 89%, positive predictive value of 91% and negative predictive value of 87% for posttransplant lymphoproliferative disorder detection by 18F-fluorodeoxyglucose-positron emission tomography. In a subanalysis of the 125 scans performed for differentiating posttransplant lymphoproliferative disorder from other diseases, sensitivity, specificity, positive predictive value and negative predictive value were 90%, 89%, 85% and 93%, respectively. 18F-fluorodeoxyglucose-uptake in posttransplant lymphoproliferative disorder was generally high with a median mean and maximum standardized uptake

  2. Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives

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    Yoon Kyung Jeon

    2017-05-01

    Full Text Available Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

  3. Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder

    Science.gov (United States)

    2013-01-24

    Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Waldenström Macroglobulinemia

  4. Pesticide exposure as a risk factor for lymphoproliferative disorders in adults.

    Science.gov (United States)

    Salem, E A; Hegazy, M M; El Khouley, E A

    2014-06-18

    In view of the widespread use of pesticides in Egypt and the increasing incidence of leukaemia and lymphoma we aimed to assess pesticide exposure and other selected variables as risk factors for lymphoproliferative disorders (leukaemia and non-Hodgkin lymphoma). In a hospital-based, retrospective, case-control study in 2011-2012, adult cases of lymphoproliferative disorders (n = 130) were recruited from outpatient clinics in Menoufia, Egypt, while controls (n = 130) were age- and sex-matched fracture patients. Family history of cancer, exposure to X-rays, smoking and use of hair dyes were not risk factors for lymphoproliferative disorders in univariate analysis. History of exposure to pesticides and HCV infection were significant risk factors for lymphoproliferative disorders in multivariate analysis (OR = 2.24; 95% CI: 1.22-4.11 and OR = 2.67; 95% CI: 1.50-4.80 respectively). The risk was significant for cases of non-Hodgkin lymphoma but not chronic lymphocytic leukaemia.

  5. Post-transplant Lymphoproliferative disorder in the United States : Young Caucasian males are at highest risk

    NARCIS (Netherlands)

    Dharnidharka, VR; Tejani, AH; Ho, PL; Harmon, WE

    2002-01-01

    We have previously documented Caucasian race and cadaver donor source as risk factors for post-transplant lymphoproliferative disorder (PTLD) development in recipients registered in the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). We analyzed data from the Scientific Regist

  6. The risk factors of post-transplant lymphoproliferative disorders following haploidentical hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    张春丽

    2014-01-01

    Objective Post-transplant lymphoproliferative disorder(PTLD)occurring after allogeneic hematopoietic stem cell transplantation(allo-HSCT)is rare but severe.Risk factors including pre-HSCT exposure variables,conditioning regimens,transplant-related complications,and post-HSCT immune reconstitution were investigated in the development of PTLD after allo-HSCT.Methods A

  7. The immunophenotypic characteristics of 260 patients with CD5~+ B cell lymphoproliferative disorders

    Institute of Scientific and Technical Information of China (English)

    易树华

    2014-01-01

    Objective To explore the immunophenotypic characteristics of CD5+B cell lymphoproliferative disorders(BLPD)of Chinese patients.Methods Immunophenotyping of bone marrow and(or)of peripheral blood was performed in patients with B-LPD by four color multiparameter flow cytometry analysis using a panel of monoclonal antibodes,and the patients clinical data were retrospectively analyzed.The difference in immunophenotypes and

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

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Bendix, Knud;

    2015-01-01

    Post-transplant lymphoproliferative disorders (PTLDs) are potentiallyfatal, 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...... 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....

  9. Post-transplant Lymphoproliferative Disorder Arising from Renal Allograft Parenchyma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byung Kwan; Kim, Chan Kyo; Kwon, Ghee Young [Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of)

    2010-06-15

    Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication that occurs in patients undergoing kidney transplantation. PTLD usually manifests as a renal hilar mass comprised of histologically B-lymphocytes. We report our experience of managing a patient with PTLD arising from renal parenchyma. Ultrasonographic and MR imaging features of this unusual PTLD suggested differentiated renal cell carcinoma arising from the renal allograft

  10. Challenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders

    OpenAIRE

    Phillips, Tycel; Devata, Sumana; Wilcox, Ryan A.

    2016-01-01

    The T-cell lymphoproliferative disorders are a heterogeneous group of non-Hodgkin’s lymphomas (NHL) for which current therapeutic strategies are inadequate, as most patients afflicted with these NHL will succumb to disease progression within 2 years of diagnosis. Appreciation of the genetic and immunologic landscape of these aggressive NHL, including PD-L1 (B7-H1, CD274) expression by malignant T cells and within the tumor microenvironment, provides a strong rationale for therapeutic targetin...

  11. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2011-01-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  12. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2014-07-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  13. Effects of oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders

    Institute of Scientific and Technical Information of China (English)

    Cataldo Di Bisceglie; Angela Bertagna; Emanuela R Composto; Fabio Lanfranco; Matteo Baldi; Giovanna Motta; Anna M Barberis

    2013-01-01

    Pretherapy sperm cryopreservation in young men is currently included in good clinical practice guidelines for cancer patients.The aim of this paper is to outline the effects of different oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders,based on an 8-year experience of the Cryopreservation Centre of a large public hospital.Two hundred and sixty-one patients with testicular neoplasia and 219 patients with lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and pretherapy semen cryopreservation were evaluated.Sperm and hormonal parameters (follicle-stimulating hormone (FSH),luteinizing hormone (LH),testosterone,inhibin B levels) were assessed prior to and 6,12,18,24 and 36 months after the end of cancer treatment.At the time of sperm collection,baseline FSH level and sperm concentration were impaired to a greater extent in patients with malignant testicular neoplasias than in patients with lymphoproliferative disorders.Toxic effects on spermatogenesis were still evident at 6 and 12 months after the end of cancer therapies,while an improvement of seminal parameters was observed after 18 months.In conclusion,an overall increase in sperm concentration was recorded about 18 months after the end of cancer treatments in the majority of patients,even if it was not possible to predict the evolution of each single case ‘a priori'.For this reason,pretherapy semen cryopreservation should be considered in all young cancer patients.

  14. Intralymphatic Spread Is a Common Finding in Cutaneous CD30+ Lymphoproliferative Disorders.

    Science.gov (United States)

    Ferrara, Gerardo; Ena, Luca; Cota, Carlo; Cerroni, Lorenzo

    2015-11-01

    An intralymphatic variant of the cutaneous CD30 lymphoproliferative disorders (cutaneous anaplastic large cell lymphoma [ALCL] and lymphomatoid papulosis [LyP]) has been described recently. We retrieved 60 cases of ALCL of the skin (primary cutaneous: 37; cases with concomitant involvement of 1 regional lymph node: 4; skin involvement from systemic disease: 4; cases with staging results unknown: 15) and 16 cases of LyP, to evaluate the presence of lymphatic vessel involvement by neoplastic cells. A D2-40 immunohistochemical staining was used to highlight lymphatic vessels. Lymphatic vessel involvement was found in 36 cases (60%) of ALCL (primary cutaneous: 24; concomitant: 3; secondary cutaneous: 4; staging unknown: 5), and in 6 cases (37.5%) of LyP. Follow-up data, available in 28 patients with ALCL and 11 with LyP, suggested that lymphatic vessel involvement had no negative prognostic implication. Our study demonstrates that cutaneous CD30 lymphoproliferative disorders are frequently characterized by involvement of the lymphatic vessels. The intralymphatic variant of ALCL and LyP may be explained, at least in part, by a particular lymphotropism of the neoplastic cells of cutaneous CD30 lymphoproliferative disorders.

  15. ROLE OF SERUM EOSINOPHILIC CATIONIC PROTEIN AND TRYPTASE IN MYELOPROLIFERATIVE AND LYMPHOPROLIFERATIVE DISORDERS

    Directory of Open Access Journals (Sweden)

    L. S. Komarova

    2008-01-01

    Full Text Available Abstract. A role of intracellular proteins of eosinophils and mast cells remains unclear in the patients with hematological neoplasia. There is a substantial evidence that eosinophils possess some common mechanisms of cooperation with mast cells. Therapeutic interventions into key events controlling eosinophil migration may be a leading factor in treatment of hypereosinophylic states in onco-hematological disorders. Due to unknown functions of eosinophils in majority of eosinophilia-associated diseases, it would be useful to establish an algorithm of accurate diagnostics in the patients with eosinophilia, in order to choose more effective treatment in future.We studied serum levels of secretable eosinophil and mast cells proteins in oncohematological patients with increased eosinophil counts. The aim of our study was to test a significance of quantitative assay for tryptase and ECP in the patients with myelo- and lymphoproliferative diseases. The study group included thirty-eight patients with oncohematological diseases, accompanied by a marked eosinophilia (> 0.4 x 109/L. Eighteen patients with bronchial asthma (BA, and eight cases of solid tumors comprised a reference group for polyclonal eosinophilia. The levels of ECP and tryptase were measured in blood serum using a commercial fluoroimmunoenzyme assay («Pharmacia», Uppsala, Sweden. Total ECP levels were markedly increased in general group with hematological malignancies (p < 0.03, , and in cases of chronic GvHD (p < 0.03, and in a sub-group with lymphoproliferative disorders (р = 0.007 as compared to the group of non-hematological diseases.Serum levels of tryptase were significantly increased in the patients with chronic GvHD after allo-HSCT and lymphoproliferative diseases, as compared to the group of patients with solid tumors (р = 0.03, as well in GvHD compared with lymphoproliferative disorders (р < 0.05.A direct correlation was found between serum ECP levels and absolute

  16. Post-transplant lymphoproliferative disorders: implications for acquired immunodeficiency syndrome-associated malignancies.

    Science.gov (United States)

    Swinnen, L J

    2001-01-01

    Post-transplant lymphoproliferative disorders (PTLDs) comprise a histologic spectrum, ranging from hyperplastic-appearing lesions to frank non-Hodgkin's lymphoma or multiple myeloma histology. Multiple clones may coexist, each representing a discrete lymphomagenic event, a situation that is unique to immunodeficiency states. The incidence varies from 1% in renal recipients to 5% in heart recipients, but can be markedly increased by the use of anti-T-cell therapies or by T-cell depletion in bone marrow transplantation. PTLD continues to arise, even many years after transplantation, and late T-cell lymphomas have recently been recognized. Pretransplant Epstein-Barr virus (EBV) seronegativity increases risk to as high as 30%-50%. PTLD has a highly variable clinical picture; certain patterns are, however, seen. Reversibility of PTLD with reduction in immunosuppressives has long been recognized. Predicting reversibility has been difficult. The presence or absence of bcl-6 mutations has recently been identified as being of predictive value. Surgical resection can be curative. Cytotoxics, although problematic, can also be curative. Long-term remission has been achieved with anti CD21 and CD24 antibodies; efficacy has been reported for interferon alfa and for rituximab. In vitro expanded EBV-specific T cells have been effective as treatment and as prophylaxis in the setting of bone marrow transplantation. EBV viral load measured in blood appears to associate with the emergence of PTLD and may facilitate prophylactic studies. PTLD is a model of immunodeficiency-related EBV lymphomagenesis. Pathogenetic, therapeutic, and prophylactic insights gained from the study of PTLD are likely to be applicable to the acquired immunodeficiency syndrome setting.

  17. Lymphoproliferative disorders in non-AIDS- associated Kaposi's ...

    African Journals Online (AJOL)

    multiple myeloma.'·5 An association ... 7 Impaired immune function appears to be ... anatomical region), 6 patients stage 11 disease (multiple skin lesions) and 3 ... COPP. Regression of leg therapy; peripheral mediastinal lymphoma; died local fields; .... treatment results in partial restoration of immune responses following ...

  18. Prevalence of occult hepatitis C virus infection in Iranian patients with lymphoproliferative disorders.

    Science.gov (United States)

    Farahani, Maryam; Bokharaei-Salim, Farah; Ghane, Masood; Basi, Ali; Meysami, Parisa; Keyvani, Hossein

    2013-02-01

    Occult HCV infection is a form of chronic HCV infection characterized by absence of detectable anti-HCV antibodies or plasma HCV-RNA but presence of HCV-RNA in liver biopsy and/or peripheral blood mononuclear cells (PBMCs). The aim of this study was to determine the presence of HCV-RNA in PBMCs of patients with lymphoproliferative disorders. One hundred and four consecutive patients with lymphoproliferative disorders admitted to Firouzgar Hospital from January 2010 to March 2011 were recruited in this cross-sectional study. A 6-ml sample of whole blood was taken from the patients, the total RNA was extracted from the samples after the separation of plasma and PBMCs. The HCV-RNA of the samples was amplified by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). The HCV genotypes of the positive samples were tested using the INNO-LiPA™ HCV II kit, and the HCV genotypes were then confirmed by sequencing of the 5'-UTR fragments after the PCR products were cloned into a pJET1.2/blunt cloning vector. The mean age of the patients was 48.3 ± 1.76 years (range: 16-83). HCV-RNA was found in PBMCs from 2 (1.9%) of the 104 patients. Genotyping showed that the patients were infected with HCV subtype 1a. One patient suffered non-Hodgkin's lymphoma and the other suffered chronic lymphocytic leukemia. Patients with lymphoproliferative disorders with negative anti-HCV antibodies and negative plasma HCV-RNA may have occult HCV infection. Therefore, in the absence of a liver biopsy, the testing of PBMCs for the detection of genomic HCV-RNA may be beneficial.

  19. What is the Incidence of Kidney Stones after Chemotherapy in Patients with Lymphoproliferative or Myeloproliferative Disorders?

    Directory of Open Access Journals (Sweden)

    Hossein S. Mirheydar

    2014-12-01

    Full Text Available Introduction This study describes the incidence and risk factors of de novo nephrolithiasis among patients with lymphoproliferative or myeloproliferative diseases who have undergone chemotherapy. Materials and Methods From 2001 to 2011, patients with lymphoproliferative or myeloproliferative disorders treated with chemotherapy were retrospectively identified. The incidence of image proven nephrolithiasis after chemotherapy was determined. Demographic and clinical variables were recorded. Patients with a history of nephrolithiasis prior to chemotherapy were excluded. The primary outcome was incidence of nephrolithiasis, and secondary outcomes were risk factors predictive of de novo stone. Comparative statistics were used to compare demographic and disease specific variables for patients who developed de novo stones versus those who did not. Results A total of 1,316 patients were identified and the incidence of de novo nephrolithiasis was 5.5% (72/1316; symptomatic stones 1.8% 24/1316. Among patients with nephrolithiasis, 72.2% had lymphoproliferative disorders, 27.8% had myeloproliferative disorders, and 25% utilized allopurinol. The median urinary pH was 5.5, and the mean serum uric acid, calcium, potassium and phosphorus levels were 7.5, 9.6, 4.3, and 3.8 mg/dL, respectively. In univariate analysis, mean uric acid (p=0.013, calcium (p<0.001, and potassium (p=0.039 levels were higher in stone formers. Diabetes mellitus (p<0.001, hypertension (p=0.003, and hyperlipidemia (p<0.001 were more common in stone formers. In multivariate analysis, diabetes mellitus, hyperuricemia, and hypercalcemia predicted stone. Conclusions We report the incidence of de novo nephrolithiasis in patients who have undergone chemotherapy. Diabetes mellitus, hyperuricemia, and hypercalcemia are patient-specific risk factors that increase the odds of developing an upper tract stone following chemotherapy.

  20. A 5-year old male with “leukemic form” of disseminated post-transplant lymphoproliferative disorder

    Directory of Open Access Journals (Sweden)

    Saadiya Haque

    2010-03-01

    Full Text Available Post-transplant lymphoproliferative disorder (PTLD represents an abnormal lymphoid proliferation that occurs in recipients of solid organ or bone marrow allograft. It includes a diverse group of diseases ranging from polymorphic B-cell hyperplasia to frank malignant lymphoma. Clinical presentation is variable, ranging from asymptomatic to generalized lymphadenopathy, mononucleosis-like syndrome, nodal or extranodal tumors (usually gastrointestinal tract, systemic lymphomatous involvement, and rare (less than 1% of cases fulminant disseminated disease. PTLD is more common in children than in adults. Younger patients usually present with mononucleosis-like symptoms. We present an unusual case of a 5-year old male who developed a widely disseminated leukemic form of PTLD, involving lymph nodes, tonsils, multiple organs, bone marrow, cerebrospinal fluid, and peripheral blood.

  1. Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder.

    Science.gov (United States)

    Magro, Cynthia; Crowson, A Neil; Kovatich, Al; Burns, Frank

    2002-08-01

    Pityriasis lichenoides (PL) is a papulosquamous disorder often considered a form of reactive dermatosis and classified with small plaque parapsoriasis (digitate dermatosis). However, some patients with PL have developed large plaque parapsoriasis (LPP) and mycosis fungoides (MF), and lymphoid atypia and T-cell clonality have been reported in lesions of PL. We set out to explore the possibility that PL is a form of T-cell dyscrasia. Cases were selected by natural language search from an outpatient dermatopathology database; 35 cases were reviewed and clinicians and patients were contacted. Hematoxylin and eosin-stained sections were examined and immunophenotyping was carried out on paraffin-embedded, formalin-fixed tissue using antibodies to CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30, and CD56. In paraffin-embedded tissue, T-cell receptor (TCR)-gamma chain rearrangement was sought through polymerase chain reaction single stranded conformational polymorphism analysis. There were 14 males and 21 females with a mean age of 40 years held clinically to have PL chronica (PLC) (28 cases) and/or PL et varioliformis acuta (PLEVA) (7 cases). Five patients developed large atrophic poikilodermatous and/or annular plaques compatible with MF and/or LPP in a background of typical PLC. All biopsies showed tropism of lymphocytes to an epidermis manifesting psoriasiform hyperplasia, dyskeratosis, parakeratosis, and intraepithelial collections of Langerhans' cells and lymphocytes mimicking Pautrier's microabascesses. Epidermal atrophy, dermal fibroplasia, poikilodermatous alterations, and a dominance of intraepidermal cerebriform cells were seen only in patients with chronic persistent disease (i.e., PLC) and in some cases corresponded with clinical progression to MF. All cases had a T cell-dominant infiltrate, with a CD7 deletion in 21 of 32 biopsies examined; the CD7-negative cells were typically the largest and most atypical forms, often in a cohesive array within the upper layers of

  2. Prevalence of occult hepatitis C virus in egyptian patients with chronic lymphoproliferative disorders.

    Science.gov (United States)

    Youssef, Samar Samir; Nasr, Aml S; El Zanaty, Taher; El Rawi, Rasha Sayed; Mattar, Mervat M

    2012-01-01

    Background. Occult hepatitis C virus infection (OCI) was identified as a new form of Hepatitis C virus (HCV), characterized by undetectable HCV antibodies and HCV RNA in serum, while HCV RNA is detectable in liver and peripheral blood cells only. Aim. The aim of this study was to investigate the occurrence of OCI in Egyptian patients with lymphoproliferative disorders (LPDs) and to compare its prevalence with that of HCV in those patients. Subjects and Methods. The current study included 100 subjects, 50 of them were newly diagnosed cases having different lymphoproliferative disorders (patients group), and 50 were apparently healthy volunteers (controls group). HCV antibodies were detected by ELISA, HCV RNA was detected in serum and peripheral blood mononuclear cells (PBMCs) by reverse transcription polymerase chain reaction(RT-PCR), and HCV genotype was detected by INNO-LiPA. Results. OCI was detected in 20% of patients group, compared to only 4% OCI in controls group. HCV was detected in 26% of patients group with a slightly higher prevalence. There was a male predominance in both HCV and OCI. All HCV positive patients were genotype 4. Conclusion. Our data revealed occurrence of occult HCV infection in Egyptian LPD patients at a prevalence of 20% compared to 26% of HCV.

  3. Prevalence of Occult Hepatitis C Virus in Egyptian Patients with Chronic Lymphoproliferative Disorders

    Directory of Open Access Journals (Sweden)

    Samar Samir Youssef

    2012-01-01

    Full Text Available Background. Occult hepatitis C virus infection (OCI was identified as a new form of Hepatitis C virus (HCV, characterized by undetectable HCV antibodies and HCV RNA in serum, while HCV RNA is detectable in liver and peripheral blood cells only. Aim. The aim of this study was to investigate the occurrence of OCI in Egyptian patients with lymphoproliferative disorders (LPDs and to compare its prevalence with that of HCV in those patients. Subjects and Methods. The current study included 100 subjects, 50 of them were newly diagnosed cases having different lymphoproliferative disorders (patients group, and 50 were apparently healthy volunteers (controls group. HCV antibodies were detected by ELISA, HCV RNA was detected in serum and peripheral blood mononuclear cells (PBMCs by reverse transcription polymerase chain reaction(RT-PCR, and HCV genotype was detected by INNO-LiPA. Results. OCI was detected in 20% of patients group, compared to only 4% OCI in controls group. HCV was detected in 26% of patients group with a slightly higher prevalence. There was a male predominance in both HCV and OCI. All HCV positive patients were genotype 4. Conclusion. Our data revealed occurrence of occult HCV infection in Egyptian LPD patients at a prevalence of 20% compared to 26% of HCV.

  4. Potential involvement of Notch1 signalling in the pathogenesis of primary cutaneous CD30-positive lymphoproliferative disorders

    DEFF Research Database (Denmark)

    Kamstrup, M.R.; Ralfkiaer, E.; Skovgaard, G.L.;

    2008-01-01

    to coexpress Notch1 and activated Akt kinase. Conclusions These results imply a potential role for the Notch signalling pathway in the pathogenesis of primary cutaneous CD30+ lymphoproliferative disorders and provide a rationale for the exploration of the activity of Notch antagonists in the therapy...

  5. HLA associations and risk of posttransplant lymphoproliferative disorder in Danish population-based cohort

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Strandhave, Charlotte

    2015-01-01

    . Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting. Methods: We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database......Background: Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell–depleting induction therapy and primary infection or reactivation of Epstein-Barr virus....... Having identified 93 PTLD patients in the cohort, we investigated the association of HLA types with PTLD, Epstein-Barr virus status and time to PTLD onset. The outcomes survival and PTLD were evaluated using Cox regression; mismatching, and the PTLD-specific mortality were evaluated in a competing risk...

  6. EBV-positive mucocutaneous ulcer in organ transplant recipients: a localized indolent posttransplant lymphoproliferative disorder.

    Science.gov (United States)

    Hart, Melissa; Thakral, Beenu; Yohe, Sophia; Balfour, Henry H; Singh, Charanjeet; Spears, Michael; McKenna, Robert W

    2014-11-01

    Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBV MCU) is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. It has not been reported in solid organ transplant recipients. We observed 7 patients with EBV MCU in a cohort of 70 transplant recipients with EBV posttransplant lymphoproliferative disorder (PTLD). Transplants included: 5 renal, 1 heart, and 1 lung. Median patient age was 61; 5 were male. EBV MCU was observed in oral mucosa in 4 and gastrointestinal tract in 3. Duration of immunosuppressive therapy before EBV MCU was 0.6 to 13 years. Ulcers were undermined by inflammatory cells and polymorphic or monomorphic large cell lymphoproliferation. Reed-Sternberg-like cells were present in 5/7. Large B cells were CD20, CD30, and EBV-encoded RNA positive in all cases. Diagnosis in 3 recent patients was EBV MCU; 4 patients diagnosed before familiarity with EBV MCU were classified as monomorphic large cell (n=3) and polymorphic (n=1) PTLD. None of the patients had EBV DNA in their blood (<1000 copies/mL) at diagnosis or follow-up versus 35/44 transplant patients with systemic PTLD (P<0.001). All lesions resolved with reduced immunosuppression (7/7), change in immunosuppression (2/7), and rituximab (3/7). Five patients are living: 4 healthy, 1 awaiting second renal transplant. Two patients died 3 and 5 years after resolution of EBV MCU. No patient recurred with EBV MCU or other PTLDs. EBV MCU mimics more aggressive categories of PTLD but lacks EBV DNA in blood, which may be a useful distinguishing feature. Lesions are likely to resolve with conservative management. Awareness of EBV MCU in the posttransplant setting is necessary for appropriate diagnosis and treatment.

  7. Small intestinal involvement by lymphoproliferative disorders post-renal transplantation: A report from the post-transplant lymphoproliferative disorder international survey

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2013-01-01

    Full Text Available In this study, data on post-renal transplant lymphoproliferative disorders (PTLD collected from the existing literature were pooled and analyzed to compare the characteristics, predictors and prognosis of small intestinal PTLDs. We performed a comprehensive search for the available data by Pubmed and Google scholar search engines for reports on this subject. Data from 18 previously published studies, comprising 120 renal allograft recipients, were included in the analysis. Renal transplant recipients with intestinal PTLD were significantly less likely to have Hogkin′s and Hogkin′s-like lesions (P = 0.044 and to be younger at the time of transplan-tation (P = 0.07. Except for Hodgkin′s-like lesions, histopathological evaluations elsewhere were comparable between the group with PTLD in the small intestine and age- and sex-matched renal transplant recipients with PTLD in other sites. The overall mortality was relatively higher in the control group (P = 0.09. When death only due to PTLD was used as the outcome, a trend toward better outcome was seen for the intestinal PTLD group compared with the other localizations (P = 0.1. The 1- and 5-year survival rates for intestinal PTLD patients were 57% and 37%, respectively, compared with 54% and 21%, respectively, for the control group. According to our findings based on analysis of international data, renal transplant patients with small intestinal PTLD are more likely to be of younger age but less frequently represent Hodgkin′s and Hodgkin′s-like lesions. They also have better patient survival compared with transplant recipients with PTLD in other locations. Further multi-center prospective studies are needed to confirm our results.

  8. Post-transplant lymphoproliferative disorder in the pelvis successfully treated with consolidative radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Habibeh, Omar; Elsayad, Khaled; Kriz, Jan; Haverkamp, Uwe; Eich, Hans Theodor [University Hospital of Muenster, Department of Radiation Oncology, Muenster (Germany)

    2017-01-15

    Post-transplant lymphoproliferative disorders (PTLDs) are aggressive malignancies which represent one of the major post-transplant complications. However, treatment options vary significantly and localized disease may be curatively treated with radiotherapy (RT) or surgery. We report a case of recurrent rectal PTLD, which was successfully treated by chemoimmunotherapy followed by RT. We describe a patient who developed a rectal lymphoproliferative lesion 11 years after kidney transplant, which was successfully treated with consolidative RT using 25.4 Gy sequential to chemoimmunotherapy (R-CHOP). RT was well tolerated and the patient showed no signs of grade 3 or 4 toxicity. This patient is free of recurrence 52 months after RT, with an overall survival of 62 months since diagnosis. Conventionally fractionated moderate-dose RT appears to be a tolerable and effective treatment option for localized PTLD if a sufficient systemic treatment cannot be applied. (orig.) [German] Posttransplantationslymphoproliferative Erkrankungen (PTLDs) sind eine haeufige Komplikation nach einer Organtransplantation. Nichtdestotrotz unterscheiden sich die Behandlungsmoeglichkeiten signifikant und vor allem lokalisierte Stadien koennen kurativ entweder mit Strahlentherapie (RT) und/oder Operation behandelt werden. Wir berichten ueber einen Fall einer rezidivierten rektalen PTLD, die erfolgreich mit einer Chemoimmuntherapie mit anschliessender RT behandelt wurde. Wir beschreiben einen Patienten der 11 Jahre nach einer Nierentransplantation eine PTLD entwickelte. Diese wurde erfolgreich mit konsolidierender RT (25,4 Gy) im Anschluss an eine Chemoimmuntherapie (R-CHOP) behandelt. Die RT wurde komplikationslos vertragen und es zeigten sich keine Nebenwirkungen. Das rezidivfreie Ueberleben betrug zum Zeitpunkt der letzten Nachsorgeuntersuchung 52 Monate mit einer Gesamtueberlebenszeit von 62 Monaten seit der Diagnose. Die konventionelle fraktionierte moderat dosierte RT scheint eine gut

  9. EBV-negative monomorphic B-cell post-transplant lymphoproliferative disorders are pathologically distinct from EBV-positive cases and frequently contain TP53 mutations.

    Science.gov (United States)

    Courville, Elizabeth L; Yohe, Sophia; Chou, David; Nardi, Valentina; Lazaryan, Aleksandr; Thakral, Beenu; Nelson, Andrew C; Ferry, Judith A; Sohani, Aliyah R

    2016-10-01

    Monomorphic post-transplant lymphoproliferative disorder commonly resembles diffuse large B-cell lymphoma or Burkitt lymphoma, and most are Epstein-Barr virus (EBV) positive. We retrospectively identified 32 cases of monomorphic post-transplant lymphoproliferative disorder from two institutions and evaluated EBV in situ hybridization; TP53 mutation status; p53, CD30, myc, and BCL2 expression by immunohistochemistry; proliferation index by Ki67; and germinal center vs non-germinal center immunophenotype by Hans criteria. Post-transplant lymphoproliferative disorder arose after hematopoietic stem cell transplant in five and solid organ transplant in 27 patients, a median of 4 and 96 months after transplant, respectively (overall median latency 71 months, range 2-295). The most common morphology was diffuse large B-cell lymphoma (28 cases), with three cases of Burkitt lymphoma, and one case of plasmablastic lymphoma. Ten cases (31%) were EBV negative. Of those with the morphology of diffuse large B-cell lymphoma, the EBV-negative cases were more frequently TP53-mutated (Pnegative (Ppost-transplant lymphoproliferative disorder were older with a longer latency from time of transplant to diagnosis (Ppost-transplant setting and underscores differences between EBV-positive and EBV-negative post-transplant lymphoproliferative disorder in terms of immunophenotype and TP53 mutation frequency, supporting an alternative pathogenesis for EBV-negative post-transplant lymphoproliferative disorder.

  10. HHV8/EBV Coinfection Lymphoproliferative Disorder: Rare Entity with a Favorable Outcome

    Directory of Open Access Journals (Sweden)

    Dhouha Bacha

    2017-01-01

    Full Text Available HHV8/EBV-associated germinotropic lymphoproliferative disorder (GLD is a challenging diagnosis given its rarity, the particular clinical presentation, and the lack of expression of markers usually used in establishing hematopoietic lineage. We report a new case of HHV8/EBV GLD in an immunocompetent 78-year-old woman. The diagnosis was made in an incidentally discovered lymphadenopathy. Histological examination showed a nodular lymphoid proliferation centered by aggregates of atypical plasmablastic cells admixed with small lymphoid cells. Tumor cells were strongly positive with EMA, HHV8, LMP1, CD38, CD138, and kappa light chains. They were negative with common lymphoma-associated markers (CD20, CD3, CD15, CD30, CD10, and bcl2. In situ hybridization confirmed the monotypic kappa light chains and the EBV infection (EBER+. A polyclonal pattern of Ig gene rearrangement was detected by PCR analysis. In the adjacent lymph node parenchyma, some germinal centers mimicked Castleman disease. In this case, the differential diagnosis was discussed with an early stage of large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease. The clinical presentation, the immunophenotype, and the molecular results helped to make the accurate diagnosis. Through the review of the nine previously reported cases in literature, we discuss the clinical and pathologic features and the differential diagnosis of HHV8/EBV GLD.

  11. Circulating antibody free light chains and risk of posttransplant lymphoproliferative disorder.

    Science.gov (United States)

    Engels, E A; Preiksaitis, J; Zingone, A; Landgren, O

    2012-05-01

    Posttransplant lymphoproliferative disorder (PTLD) is a major complication of solid-organ transplantation. With human immunodeficiency virus infection (an analogous immunosuppressive state), elevated kappa and lambda immunoglobulin free light chains (FLCs) in peripheral blood are associated with increased risk of lymphoma. To assess the role of B-cell dysfunction in PTLD, we measured circulating FLCs among Canadian transplant recipients, including 29 individuals with PTLD and 57 matched transplant recipients who were PTLD-free. Compared with controls, PTLD cases had higher kappa FLCs (median 1.53 vs. 1.07 times upper limit of normal) and lambda FLCs (1.03 vs. 0.68). Using samples obtained on average 3.5 months before PTLD diagnosis, cases were more likely to have polyclonal FLC elevations (i.e. elevated kappa and/or lambda with normal kappa/lambda ratio: odds ratio [OR] 4.2, 95%CI 1.1-15) or monoclonal elevations (elevated kappa and/or lambda with abnormal ratio: OR 3.0, 95%CI 0.5-18). Strong FLC-PTLD associations were also observed at diagnosis/selection. Among recipients with Epstein-Barr virus (EBV) DNA measured in blood, EBV DNAemia was associated with FLC abnormalities (ORs 6.2 and 3.2 for monoclonal and polyclonal elevations). FLC elevations are common in transplant recipients and associated with heightened PTLD risk. FLCs likely reflect B-cell dysfunction, perhaps related to EBV-driven lymphoproliferation.

  12. The impact of hepatitis viruses on chronic lymphoproliferative disorders; preliminary results

    Science.gov (United States)

    Ciufu, C; Neagu, AM; Onisai, M; Bumbea, H; Ciufu, C; Vintilescu, AM; Dobrea, C; Arama, V; Mihailescu, R; Arama, S

    2010-01-01

    The aim of this study is to analyze a group of patients with chronic lymphoproliferative disorders associated with B, C, D hepatitis viral infection. This group of chronic lymphoproliferative disordered patients with associated hepatitis viral infection has been diagnosed and monitored in the Hematology Department of the University Emergency Hospital of Bucharest, between December 2007 and January 2009. Our study is meant to observe the influence of the viral infection on clinical and biological evolution of the enrolled patients. The diagnosis of the chronic lymphoproliferative disorder was based on the bone marrow / lymph node biopsy and flow–cytometry analysis. The positive diagnosis for hepatitis viral infection was established by ELISA serological tests and viremia was performed by TaqMan method at INBI ‘Matei Bals’ Bucharest. The analyzed group is made up of 41 patients, 25/41 (60,97%) females and 16/41 (39,02%) males, with ages: 20–50 years old – 6/41 (14,63%), 51–70 years old – 23/41 (56,09%) and over 71 years old – 12/41 (29,26%) patients. The histological types of CLD: B–cell non–Hodgkin's lymphoma – in 28/41 (68,29%) patients, T–cell non–Hodgkin's lymphoma – 2/41 (4,87%) patients, Hodgkin's lymphoma – 2/41 (4,87%), chronic lymphocytic leukemia – 7/41 (17,07%), Waldenström disease – 2/41 (4,87%) patients. Regarding the type of CLD, 19/41 (46,34%) of the patients have an aggressive type of CLD and 22/41 (53,65%) a non–aggressive type of CLD. The hepatitis viral infection distribution in our patients: 14/41 (34,14%) have HBV infection, 24/41 (58,53%) have HCV infection, double/triple association of viral infection was found in 3/41 (7,31%) patients. Within HBV infection subgroup 9/14 (64,28%) patients have an aggressive type of CLD and 5/14 (35,71%) patients have a non–aggressive type, whereas within the group with HCV infection we found a different distribution: 9/24 (37,5%) patients with aggressive type and 15/24 (62

  13. CD8-positive T-cell lymphoproliferative disorder associated with Epstein-Barr virus-infected B-cells in a rheumatoid arthritis patient under methotrexate treatment.

    Science.gov (United States)

    Koji, Hitoshi; Yazawa, Takuya; Nakabayashi, Kimimasa; Fujioka, Yasunori; Kamma, Hiroshi; Yamada, Akira

    2016-01-01

    We report a 48-year-old female who developed lymphoproliferative disorder (LPD) during treatment of rheumatoid arthritis (RA) with methotrexate (MTX). She presented with multiple tumors in the cervical lymph nodes (LNs), multiple lung shadows and round shadows in both kidneys with pancytopenia and a high CRP level. The LN showed CD8-positive T-cell LPD associated with Epstein-Barr (EB) virus-infected B-cells. Clonality assays for immunoglobulin (Ig) heavy chain and T-cell receptor gamma (TCRγ) were negative. The cessation of MTX without chemotherapy resulted in the complete disappearance of the tumors and abnormal clinical features. We compared this case with previously published ones and discuss the pathological findings, presuming that the proliferation of CD8 T-cells was a reactive manifestation to reactivated EB virus-infected B-cells.

  14. Treatment of Recurrent Posttransplant Lymphoproliferative Disorder of the Central Nervous System with High-Dose Methotrexate

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    Clare J. Twist

    2013-01-01

    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a frequent complication of intestinal transplantation and is associated with a poor prognosis. There is currently no consensus on optimal therapy. Recurrent PTLD involving the central nervous system (CNS represents a particularly difficult therapeutic challenge. We report the successful treatment of CNS PTLD in a pediatric patient after liver/small bowel transplantation. Initial immunosuppression (IS was with thymoglobulin, solucortef, tacrolimus, and mycophenolate mofetil. EBV viremia developed 8 weeks posttransplantation, and despite treatment with cytogam and valganciclovir the patient developed a polymorphic, CD20+, EBV+ PTLD with peripheral lymphadenopathy. Following treatment with rituximab, the lymphadenopathy resolved, but a new monomorphic CD20−, EBV+, lambda-restricted, plasmacytoid PTLD mesenteric mass emerged. Complete response of this PTLD was achieved with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP chemotherapy; however, 4 months off therapy he developed CNS PTLD (monomorphic CD20−, EBV+, lambda-restricted, plasmacytoid PTLD of the brain and spine. IS was discontinued and HD-MTX (2.5–5 gm/m2/dose followed by intrathecal HD-MTX (2 mg/dose ×2-3 days Q 7–10 days per cycle was administered Q 4–7 weeks. After 3 cycles of HD-MTX, the CSF was negative for malignant cells, MRI of head/spine showed near-complete response, and PET/CT was negative. The patient remains in complete remission now for 3.5 years after completion of systemic and intrathecal chemotherapy. Conclusion. HD-MTX is an effective therapy for CNS PTLD and recurrent PTLD that have failed rituximab and CHOP chemotherapy.

  15. HLA Associations and Risk of Posttransplant Lymphoproliferative Disorder in a Danish Population-Based Cohort

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    Vase, Maja Ølholm; Maksten, Eva Futtrup; Strandhave, Charlotte; Søndergaard, Esben; Bendix, Knud; Hamilton-Dutoit, Stephen; Andersen, Claus; Møller, Michael Boe; Sørensen, Søren Schwartz; Kampmann, Jan; Eiskjær, Hans; Iversen, Martin; Weinreich, Ilse Duus; Møller, Bjarne; Jespersen, Bente; d'Amore, Francesco

    2015-01-01

    Background Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell–depleting induction therapy and primary infection or reactivation of Epstein-Barr virus. Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting. Methods We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database. Having identified 93 PTLD patients in the cohort, we investigated the association of HLA types with PTLD, Epstein-Barr virus status and time to PTLD onset. The outcomes survival and PTLD were evaluated using Cox regression; mismatching, and the PTLD-specific mortality were evaluated in a competing risk analysis. Results Risk of PTLD was associated with male sex (odds ratio, 1.70; 95% confidence interval, 1.07-2.71), and, in women, HLA-DR13 conferred an increased risk (odds ratio, 3.22; 95% confidence interval, 1.41-7.31). In multivariate analysis, HLA-B45 and HLA-DR13 remained independent predictive factors of PTLD. Mismatching in the B locus was associated with a reduced risk of PTLD (P < 0.001). Overall survival was poor after a PTLD diagnosis and was significantly worse than that in the remaining transplant cohort (P < 0.001). Conclusions Our data indicate risk-modifying HLA associations, which can be clinically useful after transplantation in personalized monitoring schemes. Given the strong linkage disequilibrium in the HLA region, the associations must be interpreted carefully. The large size, virtually complete ascertainment of cases and no loss to follow-up remain important strengths of the study. PMID:27500227

  16. Post-transplant lymphoproliferative disorder: Case reports of three children with kidney transplant

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    Spasojević-Dimitrijeva Brankica

    2014-01-01

    Full Text Available Introduction. Post-transplant lymphoproliferative disorder (PTLD is a heterogeneous group of diseases, characterized by abnormal lymphoid proliferation following transplantation. It is a disease of the immunosuppressed state, and its occurrence is mostly associated with the use of T-cell depleting agents, and also intensification of immunosuppressive regimens. In the majority of cases, PTLD is a consequence of Epstein-Barr virus (EBV infection and is a B-cell hyperplasia with CD-20 positive lymphocytes. The 2008 World Health Organization classification for lymphoid malignancies divides PTLD into four major categories: early lesions, polymorphic PTLD, monomorphic PTLD and Hodgkin PTLD. The treatment and prognosis depend on histology. The cornerstone of PTLD therapy includes reduction/withdrawal of immunosuppression, monoclonal anti CD-20 antibody (rituximab and chemotherapy. Outline of Cases. We reported here our experiences with three patients, two girls aged 7.5 and 15 and a 16-year old boy. They had different organ involvement: brain, combined spleen-liver and intestines, respectively. Even though EBV was a trigger of lymphoid proliferation as it was confirmed by histopathology or in cerebrospinal fluid, qualitative EBV-PCR was positive only in one patient at disease presentation. Reduction of immunosuppression therapy was applied in treatment of all three patients, while two of them received rituximab and ganciclovir. They had an excellent outcome besides many difficulties in diagnosis and management of disease. Conclusion. Qualitative EBV-PCR is not useful marker in pediatric transplant recipients. Our suggestion is that patients with the risk factors like T-cell depleting agents, immunosuppressant protocol or increasing immunosuppressive therapy and EBV miss-match with donor must be more accurately monitored with quantitative EBV PCR. [Projekat Ministarstva nauke Republike Srbije, br. 175085

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

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

    2014-06-01

    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.

  18. EBV-induced lymphoproliferative disorders in rheumatic patients: A systematic review of the literature.

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    Berti, Alvise; Felicetti, Mara; Peccatori, Susanna; Bortolotti, Roberto; Guella, Anna; Vivaldi, Paolo; Morelli, Luca; Barabareschi, Mattia; Paolazzi, Giuseppe

    2017-02-11

    Epstein-Barr virus (EBV) is involved in the pathogenesis of approximately 40% of lymphoproliferative disorders (LPDs) arising in patients receiving immunosuppressive treatment (IST) for rheumatic diseases, but data from large cohorts are still not available. We aimed to identify clinicopathological features, management and outcome of this condition. We reviewed all published cases of EBV-encoded RNA (EBER)-positive LPDs and included in our analysis one unpublished patient diagnosed in our Hospital. We excluded those cases without an underling rheumatic condition, a specific IST or not reporting univocal data. In the cumulative cohort of 159 patients, most were affected by rheumatoid arthritis (83.0%) and treated with methotrexate (75.4%). 68.5% of LPDs developed between the age of 40 and 70 years, after 13.3±9.6 years from rheumatic disease onset and 58.7±47.0 months of IST. LPDs were mostly B-cell lineage derived (39.0%), Ann Arbor disease's stage I (38.3%) and presented with extra-nodal involvement in 63.1%, which was most frequently represented by central nervous system (17.6%). The most common approach was IST withdrawal (93.3%), variably associated with radiotherapy(RT)/chemotherapy(CT) in 38.3% of cases. Overall, 61.7% of patients achieved a complete remission (CR; 30.2±24.0 months). Among published cases of patients that only suspended IS as first line treatment approach, 67.2% achieved CR. No significant demographic, clinical and histological differences between patients who achieved CR and who did not, and between who achieved CR by IST withdrawal alone and who did not were observed (P>0.05 in all comparison). The current study reviews all the published evidences of EBV-induced LPDs in patients receiving IST treatment for rheumatic conditions. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  19. SV40 and p53 as team players in childhood lymphoproliferative disorders.

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    Heinsohn, Susanne; Scholz, Roswitha; Kabisch, Hartmut

    2011-05-01

    Simian virus 40 (SV40) is known to be potently oncogenic and can induce several types of tumours, such as lymphoma. p53 was discovered as a cellular partner of the SV40 large T-antigen, the oncoprotein of this virus. There have not been many studies on SV40 and p53 in lymphomas and the ones that exist, are controversial. A comparison of these two components in lymphoma has not been reported previously. We examined 91 lymphomas [60 B-cell non-Hodgkin's lymphomas (B-NHLs), 19 B-cell acute lymphoblastic leukemias (B-ALLs), 7 B-cell precursor acute lymphoblastic leukemias and 5 T-cell acute lymphoblastic leukemias] for the presence of SV40. Overall, 40 samples from 12 B-NHL/19 B-ALL patients were additionally investigated for p53 mutation in the hot-spot exons 5 to 8. Overall, we found 62/91 lymphomas to be SV40-positive, among them 16/19 B-ALLs and 38/60 B-NHLs. SV40 was absent in 147 of the 149 blood control samples. We found 11 p53 mutations in 19 B-ALL patients: 5 in exon 5 (codons 132, 141, 143, 155 and 181), 4 in exon 7 (codons 236, 238 and 248), 2 in exon 8 (codon 273). In B-NHL patients we found p53-mutations in 9/12 samples: 6 of these in 3 lymph nodes (LNs). One LN harboured 3 different p53 mutations: Exon 5 (codon 132), exon 6 (codon 213) and exon 8 (codon 288). Another LN showed 2 different p53 mutations: Exon 6 (codon 213) and exon 8 (codon 285). Except for 1 nonsense mutation in an LN of a B-NHL patient, all 20 mutations were missense mutations, 2 were homozygous, both found in B-NHL-samples, and one of these (codon 175) is known to cause the global denaturation of p53. All occur in the DNA-binding domain of p53. All specimens showing a p53 mutation, were SV40-positive. p53 mutaions found in LNs of B-NHL patients harbour high SV40 copy numbers. Our data strongly support an important role for SV40, as well as a strong association of SV40 and p53 in childhood lympho-proliferative disorders.

  20. Hydroa vacciniforme-like lymphoma: a chronic EBV+ lymphoproliferative disorder with risk to develop a systemic lymphoma.

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    Quintanilla-Martinez, Leticia; Ridaura, Cecilia; Nagl, Florian; Sáez-de-Ocariz, Marimar; Durán-McKinster, Carola; Ruiz-Maldonado, Ramon; Alderete, Georgia; Grube, Peter; Lome-Maldonado, Carmen; Bonzheim, Irina; Fend, Falko

    2013-10-31

    Hydroa vacciniforme-like lymphoma (HVLL) is an Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorder of childhood that occurs mainly in Central and South America and Asia. We present the clinicopathological features of 20 Mexican children with HVLL with a median age of 8 years at diagnosis (range, 1-15). All patients presented with skin lesions involving sun-exposed areas, but not exclusively. Fever, lymphadenopathy, and hepatosplenomegaly were often observed. Most patients were treated with immunomodulators and/or immunosuppressive agents, resulting in temporary remission. For 13 patients follow-up was available for a median of 3 years (range, 1 month-13 years). Three patients with long follow-up (9-13 years) are alive with disease. Four patients died, 2 after developing systemic lymphoma. Histologically, the skin showed a predominantly angiocentric and periadnexal Epstein-Barr early RNA+ lymphoid infiltrate with variable atypia and subcutaneous involvement. Fifteen patients showed a T-cell phenotype (12, αβ; 2, γδ; 1, silent phenotype) and monoclonal T-cell receptor-γ rearrangements, whereas 6 exhibited a natural killer (NK)-cell phenotype. Four patients had hypersensitivity to mosquito bites. One patient showed both phenotypes. HVLL is an EBV-associated lymphoproliferative disorder of αβ-, γδ-, or NK-cell phenotype with a broad clinical spectrum, usually prolonged clinical course, and risk for progression to systemic disease.

  1. Association of Chronic HBV Infection with Chronic Lymphoproliferative Disorders: A Review and Case Report

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    Inna M. Mulina

    2016-06-01

    Full Text Available This article presents a clinical report on the associated course of chronic hepatitis B virus (HBV infection with Castleman's disease (CD. We noticed the reactivation of previously latent chronic hepatitis B (CHB with high replicative activity of HBV DNA during the treatment of lymphoproliferative disease. This clinical case dictates the need for pre-emptive therapy of HBV infection with nucleoside analogues in patients who are receiving chemotherapy.

  2. Associations among Epstein-Barr virus subtypes, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder in bone marrow transplant recipients

    NARCIS (Netherlands)

    Görzer, Irene; Puchhammer-Stöckl, Elisabeth; van Esser, Joost W J; Niesters, Hubert G M; Cornelissen, Jan J

    2007-01-01

    The association between Epstein-Barr virus subtype, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder was examined in a group of 25 bone marrow transplant recipients. A highly statistically significant correlation was observed between th

  3. Hematopoietic stem cell transplantation conditioning with use of rituximab in EBV related lymphoproliferative disorders.

    Science.gov (United States)

    Shamriz, Oded; Vilk, Shoshana Revel; Wolf, Dana G; Ta-Shma, Asaf; Averbuch, Diana; Weintraub, Michael; Stepensky, Polina

    2014-04-01

    X-linked lymphoproliferative disease (XLP) and IL-2-inducible T cell kinase (ITK) deficiency are rare immunodeficiencies with a spectrum of clinical manifestations. Although there are no official guidelines for allogeneic hematopoietic stem cell transplantation (HSCT) in these patients, previous reports have shown that reduced intensity conditioning regimens provide successful engraftment with limited toxicity. Here, we report on three children with XLP and one with ITK deficiency, who underwent successful HSCT using a rituximab containing conditioning regimen, and review the current literature. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. IgG4-related disease: a novel lymphoproliferative disorder discovered and established in Japan in the 21st century.

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    Masaki, Yasufumi; Kurose, Nozomu; Umehara, Hisanori

    2011-01-01

    IgG4-related disease is a novel lymphoproliferative disorder that shows hyper-IgG4-γ-globulinemia and IgG4-producing plasma cell expansion in affected organs with fibrotic or sclerotic changes. Patients show systemic inflammatory conditions and various symptoms depending on the affected organ. Since the first report of patients with elevated serum IgG4 in sclerosing pancreatitis in 2001, various systemic disorders described by many names have been reported. Despite similarities in the organs involved in IgG4-related Mikulicz's disease and Sjögren's syndrome, there are marked clinical and pathological differences between these conditions. Most patients diagnosed with autoimmune pancreatitis in Japan have IgG4-related pancreatitis [Type 1 autoimmune pancreatitis (AIP), lymphoplasmacytic sclerosing pancreatitis (LPSP)], a disease distinct from some of the western type [Type 2 AIP, idiopathic duct-centric chronic pancreatitis (IDCP), autoimmune pancreatitis with granulocytic epithelial lesions (GEL)]. Diagnosis of IgG4-related disease is characterized by both elevated serum IgG4 (>135 mg/dL) and histopathological features including lymphocyte and IgG4(+) plasma cell infiltration (IgG4(+) plasma cells/IgG(+) plasma cells>40%). Differential diagnosis from other distinct disorders, such as sarcoidosis, Castleman's disease, Wegener's granulomatosis, lymphoma, cancer, and other existing conditions associated with high serum IgG4 level or abundant IgG4-bearing plasma cells in tissues is necessary. We have begun a clinical prospective study to establish a treatment strategy (Phase II prospective treatment study for IgG4-multiorgan lymphoproliferative syndrome: UMIN R000002311).

  5. Composite Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorder and Tubular Adenoma in a Rectal Polyp.

    Science.gov (United States)

    Lo, Amy A; Gao, Juehua; Rao, M Sambasivia; Yang, Guang-Yu

    2016-02-01

    Composite tumors are formed when there is intermingling between two components of separate tumors seen histologically. Cases demonstrating composite tubular adenoma with other types of tumors in the colon are rare. Composite tubular adenomas with nonlymphoid tumors including carcinoids, microcarcinoids, and small cell undifferentiated carcinoma have been reported in the literature. The occurrence of composite lymphoma and tubular adenoma within the colorectal tract is extremely rare. Only three cases have been reported and include one case of mantle cell lymphoma and two cases of diffuse large B-cell lymphoma arising in composite tubular adenomas. We present the first case of composite Epstein-Barr virus-associated B-cell lymphoproliferative disorder and tubular adenoma in a rectal polyp with a benign endoscopic appearance.

  6. Multiple personality disorder.

    Science.gov (United States)

    Salama, A A

    1995-02-01

    This paper presents a description of Multiple Personality Disorder--its development, etiology, and presentation. The paper stresses the criteria for diagnosis that can help professionals to identify individuals at an early stage. An overview of treatment approaches and indications for hospitalization, length of treatment, and goals are also explained.

  7. Primary mucosal CD30-positive T-cell lymphoproliferative disorders of the head and neck rarely involving epiglottis: clinicopathological, immunohistomchemical and genetic features of a case.

    Science.gov (United States)

    Zhou, Jun; Wang, Guannan; Zhang, Dandan; Yin, Yuhui; Pang, Xia; Zhang, Jing; Zhang, Yanpin; Li, Wencai

    2015-01-01

    A case of primary mucosal CD30-positive T-cell lymphoproliferative disorder of the head and neck rarely involving epiglottis in a 59-year-old male was reported. Histologically, the ulcerative mucosa was affected by sheets of mixed inflammatory infiltration, with scattered large atypical lymphoid cells arranging in an individual or small clusters with focal epidermotropism. Immunohistochemically, tumor cells were uniformly immunoreactive to antibodies against CD2, CD3, CD7, CD43, CD4, TIA-1, with a heterogeneous expression of CD30, but negative for CD20, CD79a, CD21, CD8, CD56, ALK, EMA, granzyme B. Epstein-Barr virus encoded RNA (EBER) were detected. Genetically, T-cell receptor (TCR) γ gene showed an oligoclonal rearrangement. This first case developing in epiglottis demonstrates mucosal CD30-positive T-cell lymphoproliferative disorders are characteristic of a broad clinicopathologic spectrum similar to the counterpart in the skin with a favorable prognosis.

  8. [Analyses of the rearrangement of T-cell receptor- and immunoglobulin genes in the diagnosis of lymphoproliferative disorders].

    Science.gov (United States)

    Griesser, D H

    1995-01-01

    Rearrangements are developmentally regulated genetic recombinations in T and B cells which generate functional T cell receptor (TcR) and immunoglobulin genes, respectively. Different variable, sometimes diversity, and joining gene segments which are discontinuously spread out within their chromosomal location in germline configuration, are randomly assembled in individual lymphocytes. These rearrangements can be detected by Southern Blot analysis if more than 5% of a total lymphocyte population in a biopsy specimen carries the same clonal rearrangement. We analyzed DNA from 324 snap-frozen biopsy specimens from lympho-proliferative disorders. None of the 20 reactive lesions and four malignant myelomonocytic tumors had a clonal antigen receptor gene rearrangement. All 117 malignant B cell lymphomas of different subtypes and 95 of 97 malignant T cell lymphomas showed a clonal gene rearrangement. Only two angioimmunoblastic lymphadenopathy(AILD)-type T cell lymphomas did not have immune receptor gene rearrangements. They were morphologically indistinguishable from the other 47 T/AILD lymphomas with clonal rearrangement patterns. In most cases TcR beta and immunoglobulin heavy chain (IgH) gene probes were sufficient for lineage assignment of the clonal T or B lymphocyte population. In 18% of B lymphomas, however, a cross-lineage rearrangement of TcR beta genes, and in 20% of the T cell lymphomas a clonal IgH gene rearrangement was detected. After exclusion of centrocytic, large cell anaplastic lymphomas (LCAL) of B-type, and T/AILD lymphomas which are overrepresented in our study, only 10% of the remaining 147 T and B cell lymphomas had aberrant rearrangements. TcR rearrangements other than those of the beta chain genes were extremely rare in B cell lymphomas, as were Ig kappa rearrangements in T lymphomas. Only two T/AILD lymphomas had IgH and Ig kappa rearrangement in addition to their clonal T cell receptor gene rearrangements. Both samples likely contain a clonal B

  9. Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality.

    Science.gov (United States)

    Bárcena, Paloma; Jara-Acevedo, María; Tabernero, María Dolores; López, Antonio; Sánchez, María Luz; García-Montero, Andrés C; Muñoz-García, Noemí; Vidriales, María Belén; Paiva, Artur; Lecrevisse, Quentin; Lima, Margarida; Langerak, Anton W; Böttcher, Sebastian; van Dongen, Jacques J M; Orfao, Alberto; Almeida, Julia

    2015-12-15

    Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56(low) NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56(low) NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94(hi)/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.

  10. EBV-associated post-transplant lymphoproliferative disorder after umbilical cord blood transplantation in adults with hematological diseases.

    Science.gov (United States)

    Sanz, J; Arango, M; Senent, L; Jarque, I; Montesinos, P; Sempere, A; Lorenzo, I; Martín, G; Moscardó, F; Mayordomo, E; Salavert, M; Cañigral, C; Boluda, B; Salazar, C; López-Hontangas, J L; Sanz, M A; Sanz, G F

    2014-03-01

    We analyzed the incidence, clinicopathological features, risk factors and prognosis of patients with EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD) in 288 adults undergoing umbilical cord blood transplantation (UCBT) at a single institution. Twelve patients developed proven EBV-PTLD at a median time of 73 days (range, 36-812). Three-year cumulative incidence (CI) of EBV-PTLD was 4.3% (95% CI: 1.9-6.7). All patients presented with extranodal involvement. Most frequently affected sites were the liver, spleen, central nervous system (CNS), Waldeyer's ring and BM in 7, 6, 4, 3 and 3 patients, respectively. One patient had polymorphic and 11 had monomorphic EBV-PTLD (7 diffuse large B-cell lymphomas not otherwise specified, 4 plasmablastic lymphomas). We confirmed donor origin and EBV infection in all histological samples. EBV-PTLD was the cause of death in 11 patients at a median time of 23 days (range, 1-84). The 3-year CI of EBV-PTLD was 12.9% (95% CI: 3.2-22.5) and 2.6% (95% CI: 0.5-4.7) for patients receiving reduced-intensity conditioning (RIC) and myeloablative conditioning, respectively (P<0.0001). In conclusion, adults with EBV-PTLD after UCBT showed frequent visceral and CNS involvement. The prognosis was poor despite routine viral monitoring and early intervention. An increased risk of EBV-PTLD was noted among recipients of RIC regimens.

  11. Gene expression profiling reveals clear differences between EBV-positive and EBV-negative posttransplant lymphoproliferative disorders.

    Science.gov (United States)

    Morscio, J; Dierickx, D; Ferreiro, J F; Herreman, A; Van Loo, P; Bittoun, E; Verhoef, G; Matthys, P; Cools, J; Wlodarska, I; De Wolf-Peeters, C; Sagaert, X; Tousseyn, T

    2013-05-01

    Posttransplant patients are at risk of developing a potentially life-threatening posttransplantation lymphoproliferative disorder (PTLD), most often of diffuse large B cell lymphoma (DLBCL) morphology and associated with Epstein-Barr Virus (EBV) infection. The aim of this study was to characterize the clinicopathological and molecular-genetic characteristics of posttransplant DLBCL and to elucidate whether EBV(+) and EBV(-) posttransplant DLBCL are biologically different. We performed gene expression profiling studies on 48 DLBCL of which 33 arose posttransplantation (PT-DLBCL; 72% EBV+) and 15 in immunocompetent hosts (IC-DLBCL; none EBV+). Unsupervised hierarchical analysis showed clustering of samples related to EBV-status rather than immune status. Except for decreased T cell signaling these cases were inseparable from EBV(-) IC-DLBCL. In contrast, a viral response signature clearly segregated EBV(+) PT-DLBCL from EBV(-) PT-DLBCL and IC-DLBCL cases that were intermixed. The broad EBV latency profile (LMP1+/EBNA2+) was expressed in 59% of EBV(+) PT-DLBCL and associated with a more elaborate inflammatory response compared to intermediate latency (LMP1+/EBNA2-). Inference analysis revealed a role for innate and tolerogenic immune responses (including VSIG4 and IDO1) in EBV(+) PT-DLBCL. In conclusion we can state that the EBV signature is the most determining factor in the pathogenesis of EBV(+) PT-DLBCL.

  12. Clinical, laboratory, and morphological characteristics of kidney damage in lymphoproliferative disorders

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    B. T. Dzhumabaeva

    2017-01-01

    Full Text Available Kidney involvement in the onset of lymphoproliferative diseases (LPD detected rarely, observed mainly at tumor progression or relapse.Objective: to determine the clinical and morphological features of kidney damage in the initial manifestation of LPD.Materials and methods: 19 patients with LPD and kidney damage were included in the study. The diagnosis of non-Hodgkin’s lymphomas was established according to 2008 WHO classification. Histological and immunohistochemical, immunofluorescent and electron microscopic studies of nephrobiopsy have been performed.Results. Patients were aged 46-83 years (median 63 years, of which 13 were men and 6 women. Chronic lymphocytic leukemia / small cell lymphocytic lymphoma was established in 12 patients, marginal zone lymphoma – in 4 pts, follicular lymphoma – in 1 patient, Waldenstrom's macroglobulinemia – in 1 patient and diffuse large B-cell lymphoma (DLBCL in 1 patient. Proteinuria was observed in 18 patients, microhematuria – in 6 pts, arterial hypertension – in 8 pts, nephrotic syndrome – in 3 pts and renal failure in 18 patients. The mean creatinine level was 330.9 ± 52.3 µmol/L, the average glomerular filtration rate was 25.7 ± 12.9 ml/min. Monoclonal IgMκ secretion was detected in 6 patients, BJκ protein – in 9 pts, increased free light chain level – in 4 pts, cryoglobulin – in 4 pts (type II cryoglobulin in 3 of them, type I – in 1 patient.Morphological study of nephrobiopsy revealed tumor lymphoid infiltration of kidney interstitium in 10 (52.6 % cases. Diffuse small cell lymphoid proliferation was detected in 1 patient, local infiltration – in 9 pts, in 3 of them in combination with glomerulonephritis, and in 4 cases with kidney carcinoma. Local large cell lymphoid proliferation was found in 1 patient with DLBCL. Amyloidosis was detected in 2 pts and thrombotic microangiopathy – in 2 patients. Glomerulopathy was revealed in 10 patients (52.6 %: mesangioproliferative

  13. T-cell receptor gene rearrangement analysis: cutaneous T cell lymphoma, peripheral T cell lymphoma, and premalignant and benign cutaneous lymphoproliferative disorders.

    Science.gov (United States)

    Zelickson, B D; Peters, M S; Muller, S A; Thibodeau, S N; Lust, J A; Quam, L M; Pittelkow, M R

    1991-11-01

    T-cell receptor gene rearrangement analysis is a useful technique to detect clonality and determine lineage of lymphoid neoplasms. We examined 103 patients with mycosis fungoides, Sézary syndrome, peripheral T cell lymphoma, potentially malignant lymphoproliferative disorders including pre-Sézary syndrome, large plaque parapsoriasis, lymphomatoid papulosis and follicular mucinosis, and various benign inflammatory infiltrates. A clonal rearrangement was detected in skin samples in 20 of 24 patients with mycosis fungoides and in peripheral blood samples in 19 of 21 patients with Sézary syndrome. A clonal population was also detected in seven of eight cases classified as peripheral T cell lymphoma. The potentially malignant dermatoses tended to have clonal rearrangement, with the exception of large plaque parapsoriasis, and further follow-up is needed to correlate clonality with the disease course. These studies demonstrate the value of molecular genetics as an adjunct to morphology in the examination of patients with cutaneous lymphoproliferative disease.

  14. Epstein-Barr virus nuclear antigen-2 detection and typing in immunocompromised children correlated with lymphoproliferative disorder biopsy findings

    Directory of Open Access Journals (Sweden)

    Thiago Marques Mendes

    2008-06-01

    Full Text Available Epstein-Barr virus (EBV, the causative agent of infectious mononucleosis, plays a significant role as a cofactor in the process of tumorigenesis, and has consistently been associated with a variety of malignancies especially in immunocompromised patients. Forty-four children and adolescents (21 liver transplant patients, 7 heart transplant, 5 AIDS, 3 autoimmune hepatitis, 2 nephritic syndromes, 2 medullar aplasia, 2 primary immunodeficiency disorder patients, 1 thrombocytopenic purpura and 1 systemic lupus erythematosus presenting with chronic active EBV infection (VCA-IgM persistently positive; VCA-IgG > 20 AU/mL and positive IgG _ EBNA had peripheral blood samples obtained during clinically characterized EBV reactivation episodes. DNA samples were amplified in order to detect and type EBV on the basis of the EBNA-2 sequence (EBNA2 protein is essential for EBV-driven immortalization of B lymphocytes. Although we have found a predominance of type 1 EBNA-2 virus (33/44; 75%, 10 patients (22.73% carried type 2 EBNA-2, and one liver transplant patient (2.27% a mixture of the two types, the higher proportion of type 2 EBV, as well as the finding of one patient bearing the two types is in agreement with other reports held on lymphoproliferative disorder (LPD patients, which analyzed tumor biopsies. We conclude that EBNA-2 detection and typing can be performed in peripheral blood samples, and the high prevalence of type 2 in our casuistic indicates that this population is actually at risk of developing LPD, and should be monitored.

  15. Posttransplant Lymphoproliferative Disorder of the Thorax: CT and FDG-PET Features in a Single Tertiary Referral Center.

    Science.gov (United States)

    Yoon, Ga Young; Kim, Mi Young; Huh, Joo Rryung; Jo, Kyung-Wook; Shim, Tae Sun

    2015-08-01

    To investigate the chest computed tomography (CT) and F-18 fluoro-2-deoxy-D-glucose positron emission tomographic (FDG-PET) findings of posttransplant lymphoproliferative disorder (PTLD) in the thorax.From November 2004 to February 2013, the cases of 12 adult patients (3 female and 9 male, age range 34-68, and median age 46 years) with proven PTLD were retrospectively reviewed. The transplanted organs included the kidney (5/12), liver (4/12), heart (1/12), combined kidney and pancreas (1/12), and hematopoietic stem cell (1/12). We investigated the relationship of the Epstein-Barr virus (EBV) to the patients' long-term follow-up, and evaluated the characteristics of the lesions on the chest CT and FDG-PET. The lesions were classified into 2 patterns: that of lymph node and lung involvement.The interval between the transplantation and the onset of PTLD was 2 to 128 months (median, 49). Positive EBV-encoded RNA in the pathologic specimens was found in 10 patients (83.3%). Eight patients were positive for EBV PCR in their blood, and 3 patients showed seroconversion without antiviral therapy. The responses to treatment were complete in 7 cases (58.3%), partial remission in 4 cases (33.3%), and undetermined in 1 case (8.3%). The more common chest CT patterns showed lymph node involvement (10/12) rather than lung involvement (3/12). The median maximum-standardized uptake value on the FDG-PET scans was 7.7 (range, 2.7-25.5).In patients with PTLD involving the thorax, lymphadenopathy was the more common manifestation on the chest CT rather than lung involvement. The lesions showed hypermetabolism on FDG-PET.

  16. UK-based real-time lymphoproliferative disorder diagnostic service to improve the management of patients in Ghana.

    Science.gov (United States)

    Parkins, Elizabeth; Owen, Roger G; Bedu-Addo, George; Sem, Ohene Opare; Ekem, Ivy; Adomakoh, Yvonne; Bates, Imelda

    2009-07-09

    The objective of the study was to evaluate the feasibility of a UK-based real-time service to improve the diagnosis and management of lymphoproliferative disorders (LPDs) in Ghana. Adult patients reporting to hospital with a suspected LPD, during a 1 year period, were prospectively enrolled. Bone marrow and/or lymph node biopsies were posted to the Haematology Malignancy Diagnostic Service (HMDS), Leeds, UK and underwent morphological analysis and immunophenotyping. Results were returned by e-mail. The initial diagnoses made in Ghana were compared with the final HMDS diagnoses to assess the contribution of the HMDS diagnosis to management decisions. The study was conducted at the two teaching hospitals in Ghana-Komfo Anokye, Kumasi and Korle Bu, Accra. Participants comprised 150 adult patients (>/=12 years old), 79 women, median age 46 years. Bone marrow and lymph node biopsy samples from all adults presenting with features suggestive of a LPD, at the two teaching hospitals in Ghana, over 1 year were posted to a UK LPD diagnostic centre, where immunophenotyping was performed by immunohistochemistry. Molecular analysis was performed where indicated. Diagnostic classifications were made according to international criteria. Final diagnosis was compared to the initial Ghanaian diagnosis to evaluate discrepancies; implications for alterations in treatment decisions were evaluated. Median time between taking samples and receiving e-mail results in Ghana was 15 days. Concordance between initial and final diagnoses was 32% (48 of 150). The HMDS diagnosis would have changed management in 31% (46 of 150) of patients. It is feasible to provide a UK-based service for LPD diagnosis in Africa using postal services and e-mail. This study confirmed findings from wealthy countries that a specialised haematopathology service can improve LPD diagnosis. This model of Ghana-UK collaboration provides a platform on which to build local capacity to operate an international quality

  17. Post-transplantation lymphoproliferative disorders (PTLD localized in the central nervous system: Report from an international survey on PTLD

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2013-01-01

    Full Text Available Post-transplantation lymphoproliferative disorders (PTLD localized to the central nervous system (CNS is a rare but potentially fatal side-effect of immunosuppression for organ transplantation. Till now, to the best of our knowledge, the total number of such cases reported worldwide is less than 100. In this survey, we collected the data of PTLD localized to the CNS (CNS-PTLD and compared this data with other PTLD patients with localizations to other areas serving as the control group. A comprehensive search was performed for studies reporting CNS-PTLD data in the Pubmed and Google scholar search engines. Finally, international data from 21 different studies were included in the analysis. Overall, 367 patients were entered into analysis. Organ recipients with CNS-PTLD had comparable gender make up, lymphoma cell types, Epstein-Barr virus infection rate, remission and mortality rates, with PTLD patients having other localizations. Multiorgan involvement as well as disseminated lymphoma were significantly more prevalent in the control group (P <0.05. At the last follow-up, 192 (60% patients were dead (47 missing data. Irrespective of whether the overall death or only death due to PTLD was used as the final outcome, we found that the survival rates were similar for patients of the two groups (P = 0.895. Renal transplant recipients are at greater risk for developing CNS involvement by PTLD, while heart and liver recipients represent significant lower risks for the same. This study showed that PTLD patients who had CNS presentation have quite a comparable outcome compared with those with other areas of localization. However, further prospective studies are needed for reaffirming our findings.

  18. Preliminary experience on the use of PET/CT in the management of pediatric post-transplant lymphoproliferative disorder.

    Science.gov (United States)

    Guerra-García, Pilar; Hirsch, Steffen; Levine, Daniel S; Taj, Mary M

    2017-06-14

    Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication following prolonged immunosuppression. Contrary to other lymphomas, there is no standardized imaging approach to assess PTLD either at staging or for response to therapy. Positron emission tomography/computed tomography (PET/CT) is an imaging modality that has proven to be useful in lymphoma. However, there is still limited data concerning its use in pediatric PTLD. Our study evaluates the use of PET/CT in pediatric PTLD at our institution. To assess the role of PET/CT in pediatric PTLD, we reviewed the pediatric patients with PTLD who had undergone PET/CT at our institution between 2000 and 2016. Nine patients were identified. Six had PET/CT at diagnosis. All lesions seen on CT were identified with PET/CT. Fourteen PET/CTs were done during treatment. Eight PET/CTs were negative, including three where CT showed areas of uncertain significance. In these cases, PET/CT helped us to stop treatment and the patients remain in remission after a long follow-up (mean 74.3 months; range 12.4-180.9 months). PET/CT revealed additional disease in two cases, therefore treatment was intensified. Six biopsies and close follow-up was done to confirm PET/CT results. In one case, PET/CT did not identify central nervous system involvement demonstrated on magnetic resonance imaging. PET/CT may have an important role in the staging and follow-up of pediatric PTLD. In our cohort, PET/CT was helpful in staging and assessing treatment response and in clarifying equivocal findings on other imaging modalities. © 2017 Wiley Periodicals, Inc.

  19. POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS: ROLE OF VIRAL INFECTION, GENETIC LESIONS AND ANTIGEN STIMULATION IN THE PATHOGENESIS OF THE DISEASE

    Directory of Open Access Journals (Sweden)

    Daniela Capello

    2009-11-01

    Full Text Available Post-transplant lymphoproliferative disorders (PTLD are a life-threatening complication of solid organ transplantation or, more rarely, hematopoietic stem cell transplantation. The majority of PTLD is of B-cell origin and associated with Epstein–Barr virus (EBV infection. PTLD generally display involvement of extranodal sites, aggressive histology and aggressive clinical behavior. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of cMYC, BCL6, TP53, DNA hypermethylation, and aberrant somatic hypermutation of protooncogenes. The occurrence of IGV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC B-cells and their descendants both in EBV–positive and EBV–negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6+/MUM1+/-/CD138- profile reflect B-cells actively experiencing the GC reaction, and comprise diffuse large B-cell lymphoma (DLBCL centroblastic and Burkitt lymphoma. PTLD expressing the BCL6-/MUM1+/CD138- phenotype putatively derive from B-cells that have concluded the GC reaction, and comprise the majority of polymorphic PTLD and a fraction of DLBCL immunoblastic. A third group of PTLD is reminiscent of post-GC and preterminally differentiated B-cells that show the BCL6-/MUM1+/CD138+ phenotype, and are morphologically represented by either polymorphic PTLD or DLBCL immunoblastic.

  20. Characterization of the tumor microenvironment in primary cutaneous CD30-positive lymphoproliferative disorders: a predominance of CD163-positive M2 macrophages.

    Science.gov (United States)

    De Souza, Aieska; Tinguely, Marianne; Burghart, Daniel R; Berisha, Arbeneshe; Mertz, Kirsten D; Kempf, Werner

    2016-07-01

    The tumor microenvironment is essential for tumor survival, growth and progression. There are only a few studies on the tumor microenvironment in cutaneous CD30-positive lymphoproliferative disorders. We assessed the composition of the tumor microenvironment using immunohistochemistry studies in skin biopsies from cases diagnosed with lymphomatoid papulosis (LyP: 18 specimens), primary cutaneous anaplastic large-cell lymphoma (PC-ALCL: 8 specimens), and reactive diseases harboring CD30-positive cells (18 specimens). The predominant cells present in LyP and PC-ALCL were CD163+ M2 macrophages (44.7%, 35%), followed by CD8+ tumor infiltrating lymphocytes (11%, 15%), FOXP3+ T-regulatory cells (9%, 4.5%) and programmed cell death 1(PD-1) + lymphocytes (2.2%, 6.8%). In contrast, CD30-positive reactive inflammatory and infectious disorders were characterized by higher numbers of CD123+ plasmacytoid dendritic cells (6.3%) when compared to LyP (1%), and PC-ALCL (1.1%). Key differences exist between the microenvironment of CD30-positive lymphoproliferative disorders and reactive conditions harboring CD30-positive lymphocytes. The high number of tumor associated macrophages, and the close vicinity of these immune cells to the CD30-positive tumor cells might suggest that tumor associated macrophages have direct influence on tumorigenesis in LyP and ALCL. Therefore, modulation of M2 macrophages may represent a new therapeutic strategy in cutaneous CD30-positive lymphoproliferative disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Mapping the x-linked lymphoproliferative syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Skare, J.C.; Milunsky, A.; Byron, K.S.; Sullivan, J.L.

    1987-04-01

    The X-linked lymphoproliferative syndrome is triggered by Epstein-Barr virus infection and results in fatal mononucleosis, immunodeficiency, and lymphoproliferative disorders. This study shows that the mutation responsible for X-linked lymphoproliferative syndrome is genetically linked to a restriction fragment length polymorphism detected with the DXS42 probe (from Xq24-q27). The most likely recombination frequency between the loci is 4%, and the associated logarithm of the odds is 5.26. Haplotype analysis using flanking restriction fragment length polymorphism markers indicates that the locus for X-linked lymphoproliferative syndrome is distal to probe DXS42 but proximal to probe DXS99 (from Xq26-q27). It is now possible to predict which members of a family with X-linked lymphoproliferative syndrome are carrier females and to diagnose the syndrome prenatally.

  2. Autoimmune Lymphoproliferative Syndrome with Red Cell Aplasia.

    Science.gov (United States)

    Meena, K R; Bisht, Supriya; Tamaria, K C

    2015-12-01

    Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of abnormal lymphocyte apoptosis, leading to chronic lymphoproliferation. It presents as lymphadenopathy, hepatosplenomegaly and autoimmune phenomena. Pure red cell aplasia is characterized by normochromic normocytic anemia, reticulocytopenia, and absence of erythroblasts from a normal bone marrow. Only few lymphoproliferative disorders have been associated with erythroid aplasia. The authors are reporting a case of ALPS associated with red cell aplasia in a 7-y-old girl.

  3. Multiple personality disorder following childbirth.

    Science.gov (United States)

    O'Dwyer, J M; Friedman, T

    1993-06-01

    A case of multiple personality disorder is described as a coping mechanism protecting the patient from the abuse to which she was subjected throughout her life. The multiple personalities became more prominent following the birth of a severely handicapped child.

  4. POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS: ROLE OF VIRAL INFECTION, GENETIC LESIONS AND ANTIGEN STIMULATION IN THE PATHOGENESIS OF THE DISEASE

    Directory of Open Access Journals (Sweden)

    Gianluca Gaidano

    2009-11-01

    Full Text Available

    Post-transplant lymphoproliferative disorders (PTLD are a life-threatening complication of solid organ transplantation or, more rarely, hematopoietic stem cell transplantation. The majority of PTLD is of B-cell origin and associated with Epstein–Barr virus (EBV infection. PTLD generally display involvement of extranodal sites, aggressive histology and aggressive clinical behavior. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of cMYC, BCL6, TP53, DNA hypermethylation, and aberrant somatic hypermutation of protooncogenes. The occurrence of IGV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC B-cells and their descendants both in EBV–positive and EBV–negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6+/MUM1+/-/CD138- profile reflect B-cells actively experiencing the GC reaction, and comprise diffuse large B-cell lymphoma (DLBCL centroblastic and Burkitt lymphoma. PTLD expressing the BCL6-/MUM1+/CD138- phenotype putatively derive from B-cells that have concluded the GC reaction, and comprise the majority of polymorphic PTLD and a fraction of

  5. Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

    Science.gov (United States)

    Nash, Richard A; Dansey, Roger; Storek, Jan; Georges, George E; Bowen, James D; Holmberg, Leona A; Kraft, George H; Mayes, Maureen D; McDonagh, Kevin T; Chen, Chien-Shing; Dipersio, John; Lemaistre, C Fred; Pavletic, Steven; Sullivan, Keith M; Sunderhaus, Julie; Furst, Daniel E; McSweeney, Peter A

    2003-09-01

    High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk of transplant-related complications secondary to the immunosuppressed state, including Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD), but this is an unusual complication after autologous HSCT. Fifty-six patients (median age, 42 years; range, 23-61 years) with either multiple sclerosis (n = 26) or systemic sclerosis (n = 30) have been treated. The median follow-up has been 24 months (range, 2-60 months). Two patients (multiple sclerosis, n = 1; systemic sclerosis, n = 1) had significant reactivations of herpesvirus infections early after HSCT and then developed aggressive EBV-PTLD and died on days +53 and +64. Multiorgan clonal B-cell infiltrates that were EBV positive by molecular studies or immunohistology were identified at both autopsies. Both patients had positive screening skin tests for equine ATG (Atgam) and had been converted to rabbit ATG (Thymoglobulin) from the first dose. Of the other 54 patients, 2 of whom had partial courses of rabbit ATG because of a reaction to the intravenous infusion of equine ATG, only 1 patient had a significant clinical reactivation of a herpesvirus infection (herpes simplex virus 2) early after HSCT, and none developed EBV-PTLD. The T-cell count in the peripheral blood on day 28 was 0/microL in all 4 patients who received rabbit ATG; this was significantly less than in patients who received equine ATG (median, 174/microL; P =.001; Mann-Whitney ranked sum test). Although the numbers are limited

  6. Mental Disorders - Multiple Languages

    Science.gov (United States)

    ... An Introduction) - español (Spanish) MP3 Healthy Roads Media Mental Disorders: MedlinePlus Health Topic - English Enfermedades mentales: Tema de salud de MedlinePlus - español (Spanish) National Library of Medicine ...

  7. EB病毒相关淋巴增生性疾病的分类和治疗%Classification and treatment of EBV-associated lymphoproliferative disorders

    Institute of Scientific and Technical Information of China (English)

    王学文

    2009-01-01

    Since its discovery as the first human tumor associated virus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of B-cell lymphoproliferative disorders, including Burkitt' slymphoma, classic Hodgkin' s lymphoma and lymphomas arising in immunocompromised individuals (posttransplant and HIV-associated lymphoproliferative disorders). T-cell lymphoproliferative disorders that have been reported to be EBV associated include a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphoma, extranodal nasal type natural killer/T-cell lymphoma, and other rare histotypes. EBV encodes a series of products interacting with or exhibiting homology to wide variety of antiapoptotic molecules,cytokines, and signal transducers, hence promoting EBV infection, immortalization and transformation.However, the exact mechanism by which EBV promotes oncogenesis is still an area of active debate. This review is focused on the pathology, diagnosis, classification, and pathogenesis of EBV-associated lymphomas.Recent advances in EBV cell-based immunotherapy, which is beginning to show promise in the treatment of EBV-related disorders, are discussed.%自从EB病毒(EBV)作为第一种人类肿瘤病毒被发现以来,EBV已涉及广泛的B细胞淋巴增生性疾病(LPD)的发生,包括伯基特(Burkitt)淋巴瘤、经典的霍奇金淋巴瘤(cHL)及免疫减损个体发生的淋巴瘤(移植后和HIV相关的LPD).EBV相关的T细胞LPD已有报道,包括外周T细胞淋巴瘤、血管性免疫母细胞性T细胞淋巴瘤及其他罕见的组织学类型.EBV编码一系列与之相互作用或同源的产物,它包括多种抗凋亡分子、细胞因子和信号转导蛋白,从而促进EBV感染、无限增生化(永生)和转化.EBV促发肿瘤的确切机制正在被活跃地思考和讨论中.文章重点综述EBV相关淋巴瘤的病理学、诊断、分类、发病学以及以EBV的细胞为基础的免疫治疗用于EBV相关疾病,后者在临床应用中已展示希望.

  8. Dimensions of multiple personality disorder.

    Science.gov (United States)

    Murray, J B

    1994-06-01

    Research on multiple personality disorder (MPD) has burgeoned, and large-scale investigations indicate that a typical MPD patient is a woman, a victim of childhood abuse (especially sexual abuse), a person whose symptoms meet criteria for other psychiatric disorders, and a person who would employ many psychological defenses. Treatment approaches have frequently included hypnotherapy, which requires skill and caution.

  9. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines.

    Science.gov (United States)

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-07-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.

  10. Epstein-Barr virus-positive post-transplant lymphoproliferative disorder of the central nervous system, after renal transplantation with a discrepancy in viral load between peripheral blood and cerebrospinal fluid

    NARCIS (Netherlands)

    Boersma, Marijke Nynke; van der Zanden, Adri; Laverman, Gozewijn Dirk; Sanders, Jan Stephan; de Vries, Peter Alexander Marcel

    2012-01-01

    A 43-year-old female developed an EpsteinBarr virus (EBV)-positive post-transplant lymphoproliferative disorder (PTLD) in the central nervous system (CNS), 14 years after renal transplantation. One year prior to presentation, the patients treatment regimen was altered from cyclosporine, azathioprine

  11. Desordem linfoproliferativa pós-transplante em paciente pediátrico Post-transplantation lymphoproliferative disorder in pediatric patient

    Directory of Open Access Journals (Sweden)

    Paulo Manuel Pêgo Fernandes

    2006-10-01

    Full Text Available Terapias de imunossupressão, a que pacientes transplantados devem ser submetidos, os expõe a um alto risco de desenvolver desordens linfoproliferativas pós-transplante (PTLD. Descrevemos o caso de uma criança submetida a transplante cardíaco aos sete meses de idade e que acabou desenvolvendo PTLD, aos nove anos, diagnosticada por meio de retirada de nódulo pulmonar.Immunosuppressive therapy for transplanted patients exposes them to a high risk of developing posttransplantation lymphoproliferative disorders (PTLD. We report the case of a child undergoing heart transplantation at seven months of age who developed PTLD at nine years of age, diagnosed by resection of a pulmonary nodule.

  12. Post cardiac transplantation lymphoproliferative disorder presenting as t(8;14) Burkitt leukaemia/lymphoma treated with low intensity chemotherapy and rituximab.

    Science.gov (United States)

    Windebank, Kevin; Walwyn, Tom; Kirk, Richard; Parry, Gareth; Hasan, Asif; Bown, Nick; Wilkins, Bridget

    2009-09-01

    Post-transplant lymphoproliferative disorder (PTLD) occasionally presents as Burkitt lymphoma/L3 leukaemia (BLL). We reviewed records of cases of PTLD post-cardiac transplantation (1990-2007) occurring in our unit. There were 15 episodes in 13 patients including four cases of EBV-driven Burkitt-type disease with t(8;14) translocations presenting with advanced stage disease. The first case was treated with a variety of low dose chemotherapy combinations. Despite problems during therapy he obtained complete remission, but died from complications of pre-existing cardiac allograft vasculopathy 7 months later. The subsequent three cases were treated with a UKCCSG low stage lymphoma protocol, NHL 9001 and Rituximab. They remain in complete remission. In the context of PTLD the prognostic significance of advanced stage EBV-driven BLL with the t(8;14) translocation may be different to that in immunocompetent children. (c) 2009 Wiley-Liss, Inc.

  13. Monotherapy with anti-CD20 monoclonal antibody in a heart transplant recipient with sick sinus syndrome and posttransplantation lymphoproliferative disorder: a case report.

    Science.gov (United States)

    Yang, Hsiang-Yu; Ke, Hung-Yen; Hong, Gou-Jieng; Tsai, Yi-Ting; Lin, Chih-Yuan; Li, Chung-Yi; Tsai, Chien-Sung

    2009-10-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with an incidence of 0.8% to 20% in heart transplant (HTx) recipients, and standard treatment may be too toxic in some cases. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies and has been demonstrated effective in combination with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Cardiotoxicity with CHOP remains a major concern for treating HTx recipients with PTLD, however. We present a case of an HTx recipient with sick sinus syndrome and PTLD who was successfully treated with rituximab alone, avoiding the cardiotoxicity of CHOP. The cardiotoxicity induced by CHOP should be kept in mind in HTx recipients with PTLD, especially when there is an existing heart problem in such recipients. Monotherapy with rituximab can be considered a safe choice.

  14. Lack of evidence of human herpesvirus 8 DNA sequences in HIV-negative patients with various lymphoproliferative disorders of the skin.

    Science.gov (United States)

    Dupin, N; Franck, N; Calvez, V; Gorin, I; Grandadam, M; Huraux, J M; Leibowitch, M; Agut, H; Escande, J P

    1997-06-01

    Human herpesvirus 8 (HHV-8) is a new virus which has been reported in Kaposi's sarcoma and some lymphoproliferative disorders such as Castleman's disease and body-cavity-based lymphoma. Because HHV-8 shares homology with Epstein-Barr virus (EBV), we searched for the presence of HHV-8 DNA sequences in various cutaneous T- and B-cell lymphoma by the polymerase chain reaction (PCR). Forty-seven HIV-negative patients with cutaneous lymphoma or large plaque parapsoriasis were enrolled in the study. For the detection of HHV-8 DNA sequences we used PCR followed by a hybridization with a digoxigenin-labelled probe and nested-PCR. HHV-8 DNA sequences could only be detected in a patient with large plaque parapsoriasis. Our study does not suggest any direct implication of HHV-8 in the pathogenesis of most cutaneous lymphoma. Serological studies will be helpful to appreciate if there is an epidemiological link between HHV-8 and cutaneous lymphomas.

  15. Oral cyclophosphamide was effective for Coombs-negative autoimmune hemolytic anemia in CD16+CD56- chronic lymphoproliferative disorder of NK-cells.

    Science.gov (United States)

    Sekiguchi, Nodoka; Nishina, Sayaka; Kawakami, Toru; Sakai, Hitoshi; Senoo, Noriko; Senoo, Yasushi; Ito, Toshiro; Saito, Hiroshi; Nakazawa, Hideyuki; Koizumi, Tomonobu; Ishida, Fumihiro

    2016-12-27

    An 84-year-old woman was referred to our hospital presenting anemia. Her hemoglobin level was 5.8 g/dL, and white blood cell count was 9400/μL, consisting of 82% lymphocytes. Given the lymphocyte phenotype (CD2+, CD3-, CD16+, and CD56-) and negative whole blood EBV viral load, we made a diagnosis of chronic lymphoproliferative disorder of NK cells (CLPD-NK). We suspected hemolytic anemia because of the high levels of reticulocytes in the peripheral blood and the low haptoglobin value. Although the direct Coombs test was negative and there was no cold agglutination, we examined her red-blood-cell-bound IgG (RBC-IgG), which was elevated. She was diagnosed as having as Coombs-negative autoimmune hemolytic anemia (AIHA). We report the effectiveness of oral cyclophosphamide for Coombs-negative autoimmune hemolytic anemia in CLPD-NK.

  16. Role of Epstein-Barr virus status and immunophenotypic studies in the evaluation of exfoliative cytology specimens from patients with post-transplant lymphoproliferative disorders.

    Science.gov (United States)

    Gibson, Sarah E; Picarsic, Jennifer; Swerdlow, Steven H; Pantanowitz, Liron

    2016-06-01

    Post-transplant lymphoproliferative disorders (PTLDs) are well characterized in tissue sections, but their evaluation in exfoliative cytology specimens is limited. This study reports a 25-year experience with PTLDs in exfoliative cytology specimens. All solid organ or allogeneic stem cell transplant recipients with PTLDs and exfoliative cytology specimens from 1987 to 2011 were identified. The cytomorphology, Epstein-Barr virus (EBV) status, flow cytometry, immunohistochemistry, and molecular studies were reviewed from all exfoliative cytology specimens previously diagnosed as atypical lymphoid proliferations or PTLDs. A total of 55 patients (age range, 1-72 years) with PTLDs had 434 exfoliative cytology specimens. Thirty-six of the 55 patients (65%) had 54 specimens with abnormal lymphoid proliferations (12% of the specimens), and 26 of these patients had 37 specimens available for review (15 cerebrospinal fluid specimens, 12 peritoneal fluid specimens, 9 pleural fluid specimens, and 1 bronchoalveolar lavage fluid specimen). Thirty percent of the reviewed cytology specimens were diagnostic of PTLDs, including 8 cases of monomorphic post-transplant lymphoproliferative disorder (M-PTLD) with abnormal B/T-cell populations identified with flow cytometry/immunohistochemistry and 3 EBV-positive specimens with a differential diagnosis of polymorphic PTLD versus M-PTLD. All cases diagnostic of a PTLD had 1 to 3 ancillary studies performed. Forty percent of the cytology specimens (15 of 37) were suspicious for a PTLD, but ancillary studies were performed for only a third of them, and they did not support a definitive diagnosis of a PTLD. Thirty percent of the cytology specimens (11 of 37) appeared reactive, but they lacked sufficient ancillary studies to exclude a PTLD. Atypical lymphoid proliferations are common in exfoliative cytology specimens from patients with PTLDs, and they require ancillary studies at least including immunophenotyping and EBV evaluations for a

  17. Posttransplantation lymphoproliferative disease involving the pituitary gland.

    Science.gov (United States)

    Meriden, Zina; Bullock, Grant C; Bagg, Adam; Bonatti, Hugo; Cousar, John B; Lopes, M Beatriz; Robbins, Mark K; Cathro, Helen P

    2010-11-01

    Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. T-Cell lymphoproliferative disorder of hand-mirror cell morphology presenting in an eosinophilic loculated peritoneal effusion, with omental "caking"

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    Tufankjian Dearon

    2006-01-01

    Full Text Available Abstract Background Cells with "hand mirror" morphology have not, to the best of our knowledge, been described in a primary effusion sample. This paper describes a case of T-cell lymphoma with eosinophilia in a patient with suspected peritoneal carcinomatosis. Rarely, a T-cell lymphoproliferative process may mimic primary peritoneal carcinomatosis, clinically suggested by a presentation in CT imaging of omental caking with bilateral massive loculated effusions in a patient without lymphadenopathy or splenomegaly. Methods A 60 year old caucasian male presented with vague abdominal discomfort and increasing abdominal girth. Computed tomography showed a two centimeter thick omental cake and a small loculated effusion. The clinical presentation and imaging findings were most consistent with peritoneal carcinomatosis. Cytologic evaluation of the effusion was undertaken for diagnostic study. Results Rapid intraprocedural interpretation of the effusion sample showed a monomorphic population of cells with "hand-mirror" cell morphology exhibiting cytoplasmic extensions (uropodia with 3–5 course dark cytoplasmic granules and a rim of vacuolated cytoplasm capping the opposing "mirror head" side. These cells were seen within a background of mature eosinophils. Flow cytometric evaluation of the ascites fluid demonstrated an atypical T-cell population with the following immunophenotype: CD2-, CD3+, CD4-, CD5-, CD7-, CD8+, CD56+. T-cell receptor (TCR gene rearrangement was positive for clonal TCR-gamma gene rearrangement, supporting the diagnosis of a T-lymphoprolifereative disorder. Conclusion A T-cell lymphoproliferative process may present with "hand mirror" morphology in an effusion sample. These cells may show polar cytoplasmic vacuolization and 3–5 course granules within the "handle" of these unique cells. Cytoplasm shows peripheral constriction around the nucleus.

  19. Autoimmunity and lymphoproliferation markers in naïve HCV-RNA positive patients without clinical evidences of autoimmune/lymphoproliferative disorders.

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    Gulli, Francesca; Basile, Umberto; Gragnani, Laura; Fognani, Elisa; Napodano, Cecilia; Colacicco, Luigi; Miele, Luca; De Matthaeis, Nicoletta; Cattani, Paola; Zignego, Anna Linda; Rapaccini, Gian Ludovico

    2016-08-01

    HCV can lead to both chronic liver disease and B-cell lymphoproliferative disorders. A strong association exists between HCV and mixed cryoglobulinaemia (MC). Anti-nuclear antibodies (ANA), rheumatoid factor Ig-G (RF-IgG), free light chain κ and λ (FLC-κ, FLC-λ) levels and κ/λ ratio were evaluated in 50/420 subjects unexpectedly resulted anti-HCV positive after routine screenings for non-hepathological procedures. Three/fifty patients had HCV-RNA undetectable in the serum and were excluded from the analysis. Thirty-nine/fifty patients had laboratory evidence of circulating cryoglobulins without liver disease and MC-related symptoms. Among them, 17 resulted ANA-positive. The mean cryocrit was higher in ANA-positive patients, while no other demographic/clinical differences were observed between the groups. Significantly higher levels of RF-IgG were observed in ANA-positive vs ANA-negative patients. κ and λ FLC were higher in ANA-positive patients. A ROC analysis, based on ANA-positivity vs ANA-negativity, confirmed a high sensitivity and specificity of RF-IgG test. Published data concerning MC come mostly from symptomatic vasculitis. We analyzed HCV-patients without MC symptoms, founding cryoglobulins in the majority of them. The increased levels of FR-IgG and FLC in CGs-ANA-positive patients, suggest these test could be used to identify a state of silent autoimmune and/or lymphoproliferative condition before the transition to a frank disease in naïve HCV-patients without symptoms of extrahepatic manifestations. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  20. Three different histological subtypes of Epstein-Barr virus-negative post-transplant lymphoproliferative disorder in a patient with hepatitis C infection.

    Science.gov (United States)

    Kobayashi, Mikiko; Asano, Naoko; Fukushima, Mana; Honda, Takayuki

    2014-09-01

    We report a rare case in which Epstein-Barr virus (EBV)-negative polymorphic B-cell post-transplant lymphoproliferative disorder (PTLD) and EBV-negative monomorphic T-cell PTLD [anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL)] were observed simultaneously in the same cervical lymph node, 34 months after liver transplantation for hepatitis C liver cirrhosis. Although hepatitis C recurred after 2 months, he had no other complications until PTLD occurred 34 months post-transplantation. The patient underwent reduction of the immunosuppressive drug and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, and he was considered to have achieved complete remission. However, PTLD recurred, and he died 6 months after the initial diagnosis. Autopsy revealed only EBV-negative monomorphic T-cell PTLD (ALK-negative ALCL) that involved the liver, spleen, bilateral kidneys, stomach, bladder, heart, bone marrow, right ureter, and pons. Thus, recurrent PTLD may show a different histological type from the primary disorder, as PTLD has a multiclonal potentiality that causes various types of lymphomas. Therefore, it may be difficult to predict PTLD-related prognosis from the initial PTLD histological identification.

  1. Autonomic disorders in multiple sclerosis.

    Science.gov (United States)

    Lensch, E; Jost, W H

    2011-01-01

    Multiple sclerosis is an inflammatory disease leading to disseminated lesions of the central nervous system resulting in both somatomotor and autonomic disturbances. These involve the central centers of the autonomic nervous system, as well as the automatic control and pathway systems. All autonomic functions may be disordered individually or in combined form. There is no other disease with a clinical picture so multifaceted. Besides cardiovascular dysfunctions disorders of bladder and rectum have become apparent. Somatomotor and autonomic disturbances occur with similar frequency; however the focused exam often heavily favors somatomotor symptoms. Autonomic disturbances should primarily be taken into account on history taking and clinical examination. Individual diagnosis and treatment is a secondary feature. Impairments of the autonomic nervous systems in multiple sclerosis are frequently overlooked.

  2. Autonomic Disorders in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    E. Lensch

    2011-01-01

    Full Text Available Multiple sclerosis is an inflammatory disease leading to disseminated lesions of the central nervous system resulting in both somatomotor and autonomic disturbances. These involve the central centers of the autonomic nervous system, as well as the automatic control and pathway systems. All autonomic functions may be disordered individually or in combined form. There is no other disease with a clinical picture so multifaceted. Besides cardiovascular dysfunctions disorders of bladder and rectum have become apparent. Somatomotor and autonomic disturbances occur with similar frequency; however the focused exam often heavily favors somatomotor symptoms. Autonomic disturbances should primarily be taken into account on history taking and clinical examination. Individual diagnosis and treatment is a secondary feature. Impairments of the autonomic nervous systems in multiple sclerosis are frequently overlooked.

  3. A 13 year-old boy with post-transplantation lymphoproliferative disorder presenting with obscure gastrointestinal bleeding: a case report [v1; ref status: indexed, http://f1000r.es/2p0

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    Edith Y. Ho

    2014-04-01

    Full Text Available One well recognized and potentially serious complication of chronic immunosuppression in organ transplant recipients is post-transplantation lymphoproliferative disorders (PTLD. This accounts for 20% of all malignancies in transplant recipients, which is four times higher than the general population1,2. The diagnosis of PTLD is often difficult, due to various manifestations resulting in late diagnosis. We report an unusual presentation of PTLD in a pediatric patient where the diagnosis was achieved only after extensive investigation.

  4. Favorable outcome of Epstein-Barr virus-associated B-cell lymphoproliferative disorder complicated by immunoglobulin G4-related disease treated with rituximab-based therapy: a case report

    OpenAIRE

    Ueda, Koki; Ikeda, Kazuhiko; Ogawa, Kazuei; Sukegawa, Masumi; Sano, Takahiro; Kimura, Satoshi; Suzuki, Osamu; Hashimoto, Yuko; Takeishi, Yasuchika

    2016-01-01

    Background After acute infection of Epstein-Barr virus, Epstein-Barr virus-infected B cells survive but usually do not show clonal proliferation. However, Epstein-Barr virus-infected B cells occasionally acquire a proliferative capacity that provokes clonal lymphoproliferative disorders. We herein present a case with Epstein-Barr virus-infected CD30+ B cell and immunoglobulin G4+ plasmacytoid cell proliferation in the lymph nodes, suggesting a pathological and clinical interaction between Eps...

  5. Chronic hepatitis C virus infection and lymphoproliferative disorders: mixed cryoglobulinemia syndrome, monoclonal gammopathy of undetermined significance, and B-cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Caviglia, Gian Paolo; Sciacca, Claudio; Abate, Maria Lorena; Olivero, Antonella; Rosso, Chiara; Touscoz, Giovanni Antonio; Ciancio, Alessia; Rizzetto, Mario; Smedile, Antonina

    2015-04-01

    Chronic hepatitis C (CHC) has been associated with lymphoproliferative disorders (LPD) such as mixed cryoglobulinemia syndrome (MCS), monoclonal gammopathy of undetermined significance (MGUS), and B-cell non-Hodgkin lymphoma (B-NHL). The aim of the present study is to assess MCS, MGUS, and B-NHL prevalence in a cohort of CHC-infected patients and to evaluate the association of demographic, clinical, and virologic factors with the presence of LPDs. A total of 121 CHC patients with LPDs (50 M, 71 F; mean age 61.5 ± 11.8) and 130 CHC patients without extrahepatic manifestations (60 M, 70 F; mean age 60.4 ± 9.2) were retrospectively enrolled from a cohort of 1313 CHC patients between January 2006 and December 2013. Patients with LPDs included: 25 patients with MCS (9 M, 16 F; mean age 60.2 ± 1.4), 55 patients with MGUS (18 M, 37 F; mean age 61.3 ± 12.1), and 41 patients with B-NHL (23 M, 18F; mean age 62.5 ± 11.0) RESULTS: Patients with MCS (25/1313; 1.9%), MGUS (55/1313; 4.2%), and B-LNH (41/1313; 3.1%) did not differ in age, severity of liver disease, HCV genotype, and response to antiviral therapy. Using multivariate logistic regression analysis, a positive association was found between the presence of cirrhosis and MGUS (odds ratio [OR] = 2.8924, 95% confidence interval [CI] 1.2693-6.5909; P = 0.012) and between cirrhosis and B-NHL (OR = 3.9407, 95% CI 1.7226-9.0153; P = 0.001), whereas no association with MCS diagnosis emerged. Despite the pathogenetic mechanism of HCV-associated LPDs is still unclear, cirrhosis is an additional risk factor for the development of lymphoproliferative disorders in patients with chronic HCV infection. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  6. Parathyroid Disorders - Multiple Languages: MedlinePlus

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    ... Are Here: Home → Multiple Languages → All Health Topics → Parathyroid Disorders URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Parathyroid Disorders - Multiple Languages To use the sharing features ...

  7. Emotional Disorders in People with Multiple Sclerosis

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    ... and their FAMILIES EMOTIONAL DISORDERS IN PEOPLE WITH MULTIPLE SCLEROSIS This fact sheet presents the current research on emotional disorders in multiple sclerosis (MS) and summarizes the main findings of a ...

  8. Joint Disorders - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Joint Disorders URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Joint Disorders - Multiple Languages To use the sharing features on ...

  9. Epstein-Barr virus positive B-cell lymphoproliferative disorder/polymorphous B-cell lymphoma of the urinary bladder: A case report with review of literature

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    Sandhya Sundaram

    2009-01-01

    Full Text Available We report an unusual case of a localized Epstein-Barr virus (EBV-positive B cell lymphoproliferative disorder (LPD/polymorphous B cell lymphoma of the urinary bladder in a 67 years old female patient. She had no known predisposing immunodeficiencies and presented with recent onset of hematuria. The CT and cystoscopic examination revealed a localized 2.5 cm polypoid or plaque-like mucosal mass on the right posterior and lateral wall of the bladder. The biopsy sample showed a diffuse and densely polymorphous atypical lymphoid infiltrate admixed with numerous small lymphocytes, histiocytes and occasional plasma cells and neutrophils. The large atypical cells were CD20+, CD79a+, CD30+, CD43+ and they were strongly positive for EBV by in situ hybridization using anti-EBER-1 probe. Polymerase chain reaction (PCR for immunoglobulin heavy chain gene rearrangement study showed a clonal gene rearrangement. The findings indicated EBV+LPD of the bladder. Primary lymphoma of bladder is rare and primary EBV+LPD of the bladder has not been previously described. Potential misdiagnosis of poorly differentiated urothelial carcinoma can occur and accurate diagnosis depends on comprehensive immunohistochemical and molecular workups.

  10. Early Gastric Post-Transplant Lymphoproliferative Disorder and H pylori Detection after Kidney Transplantation: A Case Report and Review of the Literature

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    CL Nash

    2000-01-01

    Full Text Available The incidence of post-transplantation lymphoproliferative disorder (PTLD in the adult renal transplant population ranges from 0.7% to 4%. The majority of cases involve a single site and arise, on average, seven months after transplantation. Histopathology usually reveals B-cell proliferative disease and has been standardized into its own classification. Treatment modalities consist of decreased immunosuppression, eradication of Epstein-Barr virus, surgical resection, systemic chemotherapy and monoclonal antibody therapy; however, mortality remains high, typically with a short survival time. In patients who have undergone renal transplantation, approximately 10% of those with PTLDs present with gastrointestinal symptomatology and disease. Reported sites include the stomach, and small and large bowel. Very few cases of Helicobacter pylori or mucosal-associated lymphoid tissue have been described in association with PTLD. In the era of cyclosporine immunosuppression, the incidence of PTLD affecting the gastrointestinal tract may be increasing in comparison with the incidence seen with the use of older immunosuppression regimens. A case of antral PTLD and H pylori infection occurring three months after renal transplantation is presented, and the natural history and management of gastric PTLD are reviewed.

  11. Post-Transplant Lymphoproliferative Disorder (PTLD) Manifesting in the Oral Cavity of a 13-Year-Old Liver Transplant Recipient (LTx).

    Science.gov (United States)

    Krasuska-Sławińska, Ewa; Minko-Chojnowska, Izabela; Pawłowska, Joanna; Dembowska-Bagińska, Bożenna; Pronicki, Maciej; Olczak-Kowalczyk, Dorota

    2015-08-18

    BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a potential complication of solid organ or bone marrow transplants. The main PTLD risk factors are: the Epstein-Barr virus (EBV), transplant type, and use of immunosuppressants. It mainly consists of an uncontrolled growth of lymphocytes in transplant recipients under chronic immunosuppressive therapy. About 85% of PTLDs are EBV-containing B-cell proliferations; 14% are T-cell proliferations, of which only 40% contain EBV; and the remaining 1% is NK-cell or plasmocyte proliferations. PTLD may present various clinical manifestations, from non-specific mononucleosis-like syndrome to graft or other organ damage resulting from pathologic lymphocyte infiltration. PTLD may manifest in the oral cavity. CASE REPORT The objective of this study was to present the case of a 13-year-old female living-donor liver transplant recipient, resulting from biliary cirrhosis caused by congenital biliary atresia, with exophytic fibrous lesions on buccal mucosa and tongue. Exophytic and hyperplastic lesion of oral mucosa were removed and histopathological examination revealed polymorphic PTLD. The patient underwent 6 cycles of CHOP chemotherapy and all the oral lesions regressed completely. CONCLUSIONS All oral pathological lesions in organ transplant recipients need to be surgically removed and histopathologically examined because they present an increased risk of neoplastic transformations such as PTLD.

  12. Clinicopathological characteristics of posttransplant lymphoproliferative disorders of T-cell origin: single-center series of nine cases and meta-analysis of 147 reported cases.

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    Herreman, An; Dierickx, Daan; Morscio, Julie; Camps, Jordi; Bittoun, Emilie; Verhoef, Gregor; De Wolf-Peeters, Christiane; Sagaert, Xavier; Tousseyn, Thomas

    2013-10-01

    T-cell or natural killer (NK)-cell posttransplant lymphoproliferative disorder (T-PTLD) is a rare but severe complication after transplant. Here we present the clinicopathological features of a single-center series of nine cases. Additionally, we summarize the clinicopathological findings of 147 cases of T/NK-cell PTLD reported in the literature in an attempt to define subtype-specific characteristics. T/NK-cell PTLD occurs in patients of all ages, usually extranodally, and most frequently after kidney transplant. Organ specific incidence, however, is highest following heart transplant. Approximately one-third of T-cell PTLDs are Epstein-Barr virus (EBV)-related, with peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) being the most prevalent EBV-associated T-cell PTLD. A male predominance is observed, which is most striking in the EBV(+) group, particularly in PTCL, NOS. With a median posttransplant interval of 72 months, T-cell PTLDs are among the late-occurring PTLDs. Of the most common T-cell PTLDs, anaplastic large cell lymphoma (ALCL) has the best prognosis, whereas PTCL, NOS and hepatosplenic T-cell lymphoma (HSTCL) have the worst prognosis. EBV(+) cases seem to have a longer survival than EBV(-) cases, suggesting a different pathogenetic mechanism.

  13. A meta-analysis of potential relationship between Epstein-Barr-Encoded-RNA (EBER and onset time of post-transplant lymphoproliferative disorders

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    Hossein Khedmat

    2015-01-01

    Full Text Available Epstein-Barr virus (EBV encodes two non-polyadenylated RNAs termed EBV-encoded RNAs (EBERs. In this study, we tried to find series in which data of EBER and onset time of post-transplant lymphoproliferative disorder (PTLD for patients have been documented to conduct a meta-analysis. A comprehensive search of the literature was performed by Pubmed and Google scholar to find reports indicating test results for EBER and PTLD onset in transplant patients. PTLD was considered "early onset" when it develops within the first post-transplant year. Finally, 265 patients from 15 studies have been included in the meta-analysis. The overall meta-analysis also showed a significant relation between EBER test positivity and early-onset PTLD development [relative risk (RR: 1.36; 95% CI: 1.16-1.59; P <0.001]. The i2 index was 49.8%. Our study suggests that PTLD lesions with positive EBER test are more likely to develop within the early post-transplant period. Since early-onset PTLD is supposed to have better prognosis, having a positive EBER test might not be a bad news. However, for having a precise conclusion, prospective studies are needed to be conducted.

  14. Epstein-Barr virus-related post-transplant lymphoproliferative disorder occurring after bone marrow transplantation for aplastic anemia in Down's syndrome.

    Science.gov (United States)

    Furuya, Aya; Ishida, Mitsuaki; Hodohara, Keiko; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Nakanishi, Ryota; Harada, Ayumi; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Yoshida, Takashi; Okabe, Hidetoshi

    2014-01-01

    It is well established that Down's syndrome exhibits a predisposition to development of leukemia, however, association between aplastic anemia and Down's syndrome is exceptional. Herein, we describe a case of aplastic anemia occurring in Down's syndrome following post-transplant lymphoproliferative disorder (PTLD) after bone marrow transplantation (BMT). A 27-year-old Japanese male with Down's syndrome presented with a headache. Laboratory tests revealed severe pancytopenia, and bone marrow biopsy demonstrated hypocellular bone marrow with decrease of trilineage cells, which led to a diagnosis of aplastic anemia. One year after diagnosis, he was incidentally found to have an anterior mediastinal tumor, which was histopathologically diagnosed as seminoma. Subsequently, he received BMT from a female donor, and engraftment was observed. Three months after transplantation, he experienced cough and high fever. Biopsy specimen from the lung revealed diffuse proliferation of large-sized lymphoid cells expressing CD20 and EBER. These lymphoid cells had XY chromosomes. Thus, a diagnosis of EBV-associated PTLD was made. This is the seventh documented case of aplastic anemia occurring in Down's syndrome. Association between aplastic anemia and Down's syndrome has not been established, therefore, additional clinicopathological studies are needed. Moreover, this is the first case to undergo BMT for aplastic anemia in Down's syndrome. Although engraftment was observed, he developed EBV-positive PTLD. The neoplastic cells of the present case were considered to be of recipient origin, although the majority of PTLD cases with BMT are of donor origin.

  15. Multiple personality disorder in Japan.

    Science.gov (United States)

    Fujii, Y; Suzuki, K; Sato, T; Murakami, Y; Takahashi, T

    1998-06-01

    The aim of this study was to determine whether the features of multiple personality disorder (MPD) in Japan are similar to those in North America, although a wide disparity exists in the prevalence of MPD between the two areas. In order to describe the features of MPD in Japan, we obtained clinical data from MPD case reports, including two of our own cases, published in Japanese academic journals and compared it with the data from other countries. The cases in Japan differed significantly from those in North America in the mean number of personalities and prevalence of sexual and/or physical abuse.

  16. Epstein-Barr virus infection and gene promoter hypermethylation in rheumatoid arthritis patients with methotrexate-associated B cell lymphoproliferative disorders.

    Science.gov (United States)

    Ejima-Yamada, Kozue; Oshiro, Yumi; Okamura, Seiichi; Fujisaki, Tomoaki; Mihashi, Yasuhito; Tamura, Kazuo; Fukushige, Tomoko; Kojima, Masaru; Shibuya, Kazutoshi; Takeshita, Morishige

    2017-02-01

    We analyzed CpG-island hypermethylation status in 12 genes of paraffin-embedded tissues from 38 rheumatoid arthritis (RA) patients with methotrexate (MTX)-associated large B cell lymphoproliferative disorder (BLPD), 11 RA patients with non-MTX-associated BLPD (non-MTX-BLPD), 22 controls with diffuse large B cell lymphoma (DLBCL), and 10 controls with Epstein-Barr virus (EBV)(+) DLBCL. Among them, tumor cells from EBV(+) MTX-BLPD patients and control EBV(+) DLBCL patients had significantly lower median incidence of CpG island methylator phenotype (CIMP) than those from non-MTX-BLPD and control DLBCL groups (2.3 and 1.7 vs. 4.3 and 4.4; P < 0.01 for each). In the MTX-BLPD group, EBV(+) patients showed lower median CIMP than EBV(-) patients (2.3 vs. 3.2); they also had significantly lower hypermethylation incidence in four apoptosis-related genes, especially death-associated protein kinase (14 vs. 55 %), higher incidence of massive tumor necrosis (86 vs. 27 %), and lower BCL2 protein expression (19 vs. 86 %) than did the control DLBCL group (P < 0.01 for all). In all clinical stages, EBV(+) MTX-BLPD patients had better prognoses than the EBV(-) MTX-BLPD (P = 0.011), non-MTX-BLPD (P = 0.002), and control DLBCL groups (P = 0.015). MTX-BLPD patients without hypermethylated RAS-associated domain family-1A (RASSF1A) or O (6) -methyl guanine-DNA methyltransferase (MGMT) had significantly better prognosis than those with hypermethylation of those genes (P = 0.033). We conclude that in RA patients with MTX-BLPD, EBV infection is associated with a lower incidence of CIMP, apoptosis-related gene hypermethylation, and BCL2 expression, which can induce tumor regression by MTX withdrawal and lead to better prognoses.

  17. Virus and autoantigen-specific CD4+ T cells are key effectors in a SCID mouse model of EBV-associated post-transplant lymphoproliferative disorders.

    Science.gov (United States)

    Linnerbauer, Stefanie; Behrends, Uta; Adhikary, Dinesh; Witter, Klaus; Bornkamm, Georg W; Mautner, Josef

    2014-05-01

    Polyclonal Epstein-Barr virus (EBV)-infected B cell line (lymphoblastoid cell lines; LCL)-stimulated T-cell preparations have been successfully used to treat EBV-positive post-transplant lymphoproliferative disorders (PTLD) in transplant recipients, but function and specificity of the CD4+ component are still poorly defined. Here, we assessed the tumor-protective potential of different CD4+ T-cell specificities in a PTLD-SCID mouse model. Injection of different virus-specific CD4+ T-cell clones showed that single specificities were capable of prolonging mouse survival and that the degree of tumor protection directly correlated with recognition of target cells in vitro. Surprisingly, some CD4+ T-cell clones promoted tumor development, suggesting that besides antigen recognition, still elusive functional differences exist among virus-specific T cells. Of several EBV-specific CD4+ T-cell clones tested, those directed against virion antigens proved most tumor-protective. However, enriching these specificities in LCL-stimulated preparations conferred no additional survival benefit. Instead, CD4+ T cells specific for unknown, probably self-antigens were identified as principal antitumoral effectors in LCL-stimulated T-cell lines. These results indicate that virion and still unidentified cellular antigens are crucial targets of the CD4+ T-cell response in this preclinical PTLD-model and that enriching the corresponding T-cell specificities in therapeutic preparations may enhance their clinical efficacy. Moreover, the expression in several EBV-negative B-cell lymphoma cell lines implies that these putative autoantigen(s) might also qualify as targets for T-cell-based immunotherapy of virus-negative B cell malignancies.

  18. Rorschach indicators of Multiple Personality Disorder.

    Science.gov (United States)

    Labott, S M; Leavitt, F; Braun, B G; Sachs, R G

    1992-08-01

    The increase in reported cases of Multiple Personality Disorder underscores a great need to differentiate clearly this from other psychiatric disorders and from simulation of Multiple Personality Disorder. Two sets of Rorschach signs have been advanced as clinical markers by their developers, namely Barach and also Wagner, Allison, and Wagner. As the Wagner signs are prevalent in much of the research on Rorschach responses in Multiple Personality Disorder, the purpose of the present study was to evaluate these signs using Wagner's administration and the resulting Rorschach protocols of 16 Multiple Personality Disorder patients and 16 psychiatric controls. Analysis indicated that this system was deficient in correctly classifying these 32 protocols. A new marker, the Splitting Response, emerged, however, which was more useful. This response, in combination with at least one Dissociative response, produced an accuracy rate of 94%. These new criteria may be useful aids in the detection of Multiple Personality Disorder from Rorschach protocols. Replication is urged.

  19. A Novel and Likely Inherited Lymphoproliferative Disease in British Shorthair Kittens.

    Science.gov (United States)

    Aberdein, D; Munday, J S; Fairley, R A; Vernau, W; Thompson, K G

    2015-11-01

    An unusual lymphoproliferative disease was identified in multiple closely related British Shorthair (BSH) kittens, suggesting an inherited predisposition to disease. Affected kittens typically developed rapidly progressive and marked generalized lymphadenopathy, moderate splenomegaly, and regenerative and likely hemolytic anemia from 6 weeks of age. Microscopic findings were suggestive of multicentric T-cell lymphoma, but additional testing revealed a polyclonal population of CD3+/CD4-/CD8- "double negative" T cells (DNT cells). This is a novel disease presentation with similarities to the human disorder autoimmune lymphoproliferative syndrome (ALPS), a rare inherited disease causing lymphoproliferation and variable manifestations of autoimmunity. The human disease is most commonly due to the presence of Fas gene mutations causing defective lymphocyte apoptosis, and further investigations of both the mode of inheritance and genetic basis for disease in affected cats are currently in progress.

  20. Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS).

    Science.gov (United States)

    Li, Pu; Huang, Ping; Yang, Ye; Hao, Mu; Peng, Hongwei; Li, Fei

    2016-02-01

    Autoimmune lymphoproliferative syndrome (ALPS), a disorder characterized by immune dysregulation due to disrupted lymphocyte homeostasis, is mainly resulted from the mutations in FAS-mediated apoptotic pathway. In addition, other mutations of the genes such as Fas-ligand (FASLG), Caspase 10 (CASP10) and Caspase 8 (CASP8), NRAS and KRAS have also been observed in a small number of patients with ALPS or ALPS-related disorders. However, approximately 20-30% of patients with ALPS have unidentified defect. Its clinical manifestations observed in multiple family members include unexplained lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias such as thrombocytopenia, neutropenia, and anemia due to excessive production of antibodies by lymphocytes, elevated number of double-negative T (DNT) cells, and increased risk of lymphoma. As a very rare disease, ALPS was first characterized in the early 1990s. More than 300 families with hereditary ALPS have been reported till now; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years. ALPS has historically considered as a primary immune defect presenting in early childhood, however, recent studies have shown that it may be more common than previous thought because adult onset presentation is increasingly becoming recognized and more adult ALPS patients are diagnosed. The new genetic and biological insights have improved the understanding of ALPS and a number of targeted therapeutic strategies such as mycophenolate mofetil, sirolimus, and pentostatin have been successfully applied in ALPS patients with promising treatment efficacy. This article comprehensively reviews the clinical and laboratory manifestations, new research advances in the molecular pathogenesis, diagnosis and treatments of this disorder.

  1. CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder.

    Science.gov (United States)

    Lefèvre, Guillaume; Copin, Marie-Christine; Roumier, Christophe; Aubert, Hélène; Avenel-Audran, Martine; Grardel, Nathalie; Poulain, Stéphanie; Staumont-Sallé, Delphine; Seneschal, Julien; Salles, Gilles; Ghomari, Kamel; Terriou, Louis; Leclech, Christian; Morati-Hafsaoui, Chafika; Morschhauser, Franck; Lambotte, Olivier; Ackerman, Félix; Trauet, Jacques; Geffroy, Sandrine; Dumezy, Florent; Capron, Monique; Roche-Lestienne, Catherine; Taieb, Alain; Hatron, Pierre-Yves; Dubucquoi, Sylvain; Hachulla, Eric; Prin, Lionel; Labalette, Myriam; Launay, David; Preudhomme, Claude; Kahn, Jean-Emmanuel

    2015-08-01

    The CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3(-)CD4(+) T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome. Atypical CD4(+) T cells lymphoid infiltrates were found in 10 of 12 CD3(-)CD4(+) L-HES patients, in lymph nodes (n=4 of 4 patients), in skin (n=9 of 9) and other extra-nodal tissues (gut, lacrymal gland, synovium). Lymph nodes displayed infiltrates limited to the interfollicular areas or even an effacement of nodal architecture, associated with proliferation of arborizing high endothelial venules and increased follicular dendritic cell meshwork. Analysis of 2 fresh skin samples confirmed the presence of CD3(-)CD4(+) T cells. Clonal T cells were detected in at least one tissue in 8 patients, including lymph nodes (n=4 of 4): the same clonal T cells were detected in blood and in at least one biopsy, with a maximum delay of 23 years between samples. In the majority of cases, circulating CD3(-)CD4(+) T cells were CD2(hi) (n=9 of 14), CD5(hi) (n=12 of 14), and CD7(-)(n=4 of 14) or CD7(low) (n=10 of 14). Angio-immunoblastic T-cell lymphoma can also present with CD3(-)CD4(+) T cells; despite other common histopathological and immunophenotypic features, CD10 expression and follicular helper T-cell markers were not detected in lymphoid variant of hypereosinophilic syndrome patients, except in both patients who developed angio-immunoblastic T-cell lymphoma, and only at T-cell lymphoma diagnosis. Taken together, persistence of tissular clonal T cells and histopathological features define CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome as a peripheral indolent clonal T-cell lymphoproliferative

  2. Favorable outcome of Epstein-Barr virus-associated B-cell lymphoproliferative disorder complicated by immunoglobulin G4-related disease treated with rituximab-based therapy: a case report.

    Science.gov (United States)

    Ueda, Koki; Ikeda, Kazuhiko; Ogawa, Kazuei; Sukegawa, Masumi; Sano, Takahiro; Kimura, Satoshi; Suzuki, Osamu; Hashimoto, Yuko; Takeishi, Yasuchika

    2016-08-24

    After acute infection of Epstein-Barr virus, Epstein-Barr virus-infected B cells survive but usually do not show clonal proliferation. However, Epstein-Barr virus-infected B cells occasionally acquire a proliferative capacity that provokes clonal lymphoproliferative disorders. We herein present a case with Epstein-Barr virus-infected CD30+ B cell and immunoglobulin G4+ plasmacytoid cell proliferation in the lymph nodes, suggesting a pathological and clinical interaction between Epstein-Barr virus-associated B-cell lymphoproliferative disorders and immunoglobulin G4-related disease. Immunoglobulin G4-related disease has been recognized as a benign disease with proliferation of IgG4-related disease+ plasmacytoid cells. Several studies have recently reported the coexistence of immunoglobulin G4-related disease+ plasmacytoid cells with Epstein-Barr virus-infected B cells in lymph nodes in some immunoglobulin G4-related disease cases. However, the pathogenic role of the clonal proliferation of Epstein-Barr virus-infected B cells in immunoglobulin G4-related disease, as well as the treatments for patients with both Epstein-Barr virus-infected B cells and immunoglobulin G4-related disease, have never been discussed. A 50-year-old Japanese man was referred to us for persistent fatigue and lymphadenopathy. His blood examination showed elevated IgG4, and detected high levels of Epstein-Barr virus DNA. A lymph node biopsy revealed IgG4+ plasmacytoid cells and infiltration of large lymphoid cells, which were positive for CD20, CD30, Epstein-Barr virus-related late membrane protein 1, and Epstein-Barr virus-encoded RNA, and were negative for IgG4. Based on the diagnosis of both Epstein-Barr virus-associated B-cell lymphoproliferative disorder and IgG4-related disease, the patient received eight cycles of rituximab combined with cyclophosphamide and prednisolone, which resulted in the complete disappearance of lymphadenopathy. Moreover, his serum IgG4 level was significantly

  3. Autoimmune lymphoproliferative syndrome (ALPS): a rare cause of immune cytopenia.

    Science.gov (United States)

    John, M Joseph; Rajasekhar, Reena; Mathews, Vikram

    2008-02-01

    Autoimmune Lymphoproliferative syndrome (ALPS) is an inherited disorder manifesting with autoimmune cytopenia, lymphadenopathy and splenomegaly. The differential diagnosis includes infections, autoimmune disorders or malignancies. The disease is characterized by accumulation of double negative (CD3+ CD4- CD8-) T cells (DNT) in the peripheral blood. We describe a case and review the literature.

  4. Detection of EBV genomes in plasmablasts/plasma cells and non-B cells in the blood of most patients with EBV lymphoproliferative disorders by using Immuno-FISH.

    Science.gov (United States)

    Calattini, Sara; Sereti, Irini; Scheinberg, Philip; Kimura, Hiroshi; Childs, Richard W; Cohen, Jeffrey I

    2010-11-25

    Epstein-Barr virus (EBV) is present in B cells in the blood of healthy people; few studies have looked for EBV in other cell types in blood from patients with lymphoproliferative disorders. We use a new technique combining immunofluorescent cell-surface staining and fluorescent in situ hybridization to quantify both EBV copy number per cell and cell types in blood from patients with high EBV DNA loads. In addition to CD20(+) B cells, EBV was present in plasmablast/plasma cells in the blood of 50% of patients, in monocytes or T cells in a small proportion of patients, and in "non-B, non-T, non-monocytes" in 69% of patients. The mean EBV copy number in B cells was significantly higher than in plasmablast/plasma cells. There was no correlation between EBV load and virus copy number per cell. Although we detected CD21, the EBV B-cell receptor, on EBV-infected B cells, we could not detect it on virus-infected T cells. These findings expand the range of cell types infected in the blood. Determining the number of EBV genomes per cell and the type of cells infected in patients with high EBV loads may provide additional prognostic information for the development of EBV lymphoproliferative diseases.

  5. Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS).

    Science.gov (United States)

    Teachey, David T; Obzut, Dana A; Axsom, Kelly; Choi, John K; Goldsmith, Kelly C; Hall, Junior; Hulitt, Jessica; Manno, Catherine S; Maris, John M; Rhodin, Nicholas; Sullivan, Kathleen E; Brown, Valerie I; Grupp, Stephan A

    2006-09-15

    Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by defective Fas-mediated apoptosis, leading to lymphadenopathy, hepatosplenomegaly, and an increased number of double-negative T cells (DNTs). Treatment options for patients with ALPS are limited. Rapamycin has been shown to induce apoptosis in normal and malignant lymphocytes. Since ALPS is caused by defective lymphocyte apoptosis, we hypothesized that rapamycin would be effective in treating ALPS. We tested this hypothesis using rapamycin in murine models of ALPS. We followed treatment response with serial assessment of DNTs by flow cytometry in blood and lymphoid tissue, by serial monitoring of lymph node and spleen size with ultrasonography, and by enzyme-linked immunosorbent assay (ELISA) for anti-double-stranded DNA (dsDNA) antibodies. Three-dimensional ultrasound measurements in the mice correlated to actual tissue measurements at death (r = .9648). We found a dramatic and statistically significant decrease in DNTs, lymphadenopathy, splenomegaly, and autoantibodies after only 4 weeks when comparing rapamycin-treated mice with controls. Rapamycin induced apoptosis through the intrinsic mitochondrial pathway. We compared rapamycin to mycophenolate mofetil, a second-line agent used to treat ALPS, and found rapamycin's control of lymphoproliferation was superior. We conclude that rapamycin is an effective treatment for murine ALPS and should be explored as treatment for affected humans.

  6. [Differential diagnosis of dissociative identity disorder (multiple personality disorder)].

    Science.gov (United States)

    Stübner, S; Völkl, G; Soyka, M

    1998-05-01

    Recently the concept of dissociative identity disorder (formerly known as multiple personality disorder) has attracted increasing public and scientific interest. However, it is rarely diagnosed in the clinical setting. the reported case of a 47-year-old woman with a history of child abuse demonstrates the problems of differential diagnosis. A number of psychopathologic symptoms pointed to a multiple personality disorder, but in the follow-up psychotic symptoms such as delusions, possible hallucinations and bizarre behavior clearly emerged. The differential diagnosis of dissociative identity disorder includes paranoid schizophrenia, as in the case described, borderline personality disorder, hysteria, simulation and the false memory syndrome. Finally, social and cultural factors have to be considered.

  7. Multiple Personality Disorder: Concepts and Cases.

    Science.gov (United States)

    Lindsley, Hope L.

    1992-01-01

    Presents two case examples illustrating nature and etiology of multiple personality disorder in two clients and describing their entry into counseling and progress through treatment. Compares and contrasts cases in areas of diagnosis, symptoms, history, and treatment. Suggests that mental health counselors combine firmness with flexibility in…

  8. Multiple Personality Disorder: Concepts and Cases.

    Science.gov (United States)

    Lindsley, Hope L.

    1992-01-01

    Presents two case examples illustrating nature and etiology of multiple personality disorder in two clients and describing their entry into counseling and progress through treatment. Compares and contrasts cases in areas of diagnosis, symptoms, history, and treatment. Suggests that mental health counselors combine firmness with flexibility in…

  9. Genetic variations in multiple myeloma I

    DEFF Research Database (Denmark)

    Vangsted, A.; Klausen, T.W.; Vogel, Ulla Birgitte

    2012-01-01

    Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis...

  10. A case of age-related Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disorder, so-called polymorphous subtype, of the mandible, with a review of the literature.

    Science.gov (United States)

    Kikuchi, Kentaro; Fukunaga, Shuichi; Inoue, Harumi; Miyazaki, Yuji; Kojima, Masaru; Ide, Fumio; Kusama, Kaoru

    2013-06-01

    Epstein-Barr virus (EBV) is known to be associated with the development of lymphomas in immunocompromised patients. Recently, age-related immune impairment has been recognized as a predisposing factor in the development of EBV-driven lymphoproliferative disorders (LPDs) in elderly patients without any known immunodeficiency or prior lymphoma. In approximately 70% of reported cases, the affected sites have been extranodal, such as the skin, lung, tonsil and stomach. However, age-related EBV-associated B cell (EBV + B cell) LPD is extremely rare in the oral cavity. Here we report a 71-year-old Japanese man who developed an EBV + B cell LPD resembling classical Hodgkin lymphoma (CHL)--so-called polymorphous subtype-of the mandible. Histopathologically, infiltration of large atypical lymphoid cells including Hodgkin or Reed-Sternberg-like cells into granulation tissue with marked necrosis was found in the mandibular bone. Immunohistochemical analysis revealed that the large atypical Hodgkin or Reed-Sternberg-like cells were CD3-, CD15-, CD20+, CD30+ and Epstein-Barr virus (EBV)-latent infection membrane protein-1 (LMP-1)+. In situ hybridization (ISH) demonstrated EBV-encoded small RNA (EBER) + in numerous Hodgkin or Reed-Sternberg-like cells. EBNA-2 was detected by polymerase chain reaction (PCR) using an extract from the formalin-fixed, paraffin-embedded specimen. To our knowledge, this is the first reported case of the polymorphous subtype of age-related EBV + B cell LPD affecting the mandible.

  11. Comparison of two real-time quantitative polymerase chain reaction strategies for minimal residual disease evaluation in lymphoproliferative disorders: correlation between immunoglobulin gene mutation load and real-time quantitative polymerase chain reaction performance.

    Science.gov (United States)

    Della Starza, Irene; Cavalli, Marzia; Del Giudice, Ilaria; Barbero, Daniela; Mantoan, Barbara; Genuardi, Elisa; Urbano, Marina; Mannu, Claudia; Gazzola, Anna; Ciabatti, Elena; Guarini, Anna; Foà, Robin; Galimberti, Sara; Piccaluga, Pierpaolo; Gaidano, Gianluca; Ladetto, Marco; Monitillo, Luigia

    2014-09-01

    We compared two strategies for minimal residual disease evaluation of B-cell lymphoproliferative disorders characterized by a variable immunoglobulin heavy chain (IGH) genes mutation load. Twenty-five samples from chronic lymphocytic leukaemia (n = 18) or mantle cell lymphoma (n = 7) patients were analyzed. Based on IGH variable region genes, 22/25 samples carried > 2% mutations, 20/25 > 5%. In the IGH joining region genes, 23/25 samples carried > 2% mutations, 18/25 > 5%. Real-time quantitative polymerase chain reaction was performed on IGH genes using two strategies: method A utilizes two patient-specific primers, whereas method B employs one patient-specific and one germline primer, with different positions on the variable, diversity and joining regions. Twenty-three samples (92%) resulted evaluable using method A, only six (24%) by method B. Method B poor performance was specifically evident among mutated IGH variable/joining region cases, although no specific mutation load above, which the real-time quantitative polymerase chain reaction failed was found. The molecular strategies for minimal residual disease evaluation should be adapted to the B-cell receptor features of the disease investigated.

  12. Methotrexate-related Epstein-Barr Virus (EBV)-associated lymphoproliferative disorder--so-called "Hodgkin-like lesion"--of the oral cavity in a patient with rheumatoid arthritis.

    Science.gov (United States)

    Kikuchi, Kentaro; Miyazaki, Yuji; Tanaka, Akio; Shigematu, Hisao; Kojima, Masaru; Sakashita, Hideaki; Kusama, Kaoru

    2010-12-01

    Patients affected by autoimmune diseases (rheumatoid arthritis, psoriasis, dermatomyositis) who are treated with methotrexate (MTX) sometimes develop lymphoproliferative disorders (LPDs). In approximately 40% of reported cases, the affected sites have been extranodal, and have included the gastrointestinal tract, skin, lung, kidney, and soft tissues. However, MTX-associated LPD (MTX-LPD) is extremely rare in the oral cavity. Here we report a 69-year-old Japanese woman with rheumatoid arthritis (RA) who developed MTX-LPD resembling Hodgkin's disease--so-called "Hodgkin-like lesion"--in the left upper jaw. Histopathologically, large atypical lymphoid cells including Hodgkin or Reed-Sternberg-like cells were found to have infiltrated into granulation tissue in the ulcerative oral mucosa. Immunohistochemistry showed that the large atypical cells were positive for CD20, CD30 and Epstein-Barr virus (EBV)-latent infection membrane protein-1 (LMP-1) and negative for CD15. EBV was detected by in situ hybridization (ISH) with EBV-encoded small RNA (EBER), and polymerase chain reaction (PCR) for LMP-1 and EBNA-2 in material taken from the formalin-fixed, paraffin-embedded specimen. To our knowledge, this is the first reported case of MTX-related EBV-associated LPD (MTX-EBVLPD), "Hodgkin-like lesion", of the oral cavity in a patient with RA.

  13. EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report

    Directory of Open Access Journals (Sweden)

    Niedobitek Gerald

    2010-03-01

    Full Text Available Abstract Epstein-Barr virus (EBV-associated B-cell post-transplantation lymphoproliferative disorder (PTLD is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD. We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD.

  14. Child abuse as an antecedent of multiple personality disorder.

    Science.gov (United States)

    Baldwin, L C

    1990-11-01

    Until recently, few cases of multiple personality disorder were diagnosed in children. Today, the number of cases is increasing at an alarming rate and appears to be most closely associated with repeated sexual and physical abuse. This paper focuses on reports of childhood multiple personality disorder in the literature, the etiology of this disorder, family dynamics, the differences between childhood and adult multiple personality disorder, credibility problems in children, reasons for failure to diagnose multiple personality disorder in children, treatment, and signs and symptoms to look for in the clinical setting.

  15. MULTIPLE PERSONALITY DISORDER FOLLOWING CONVERSION AND DISSOCIATIVE DISORDER NOS : A CASE REPORT

    OpenAIRE

    Jhingan, Harsh Prem; Aggarwal, Neeruj; Saxena, Shekhar; Gupta, Dhanesh K

    2000-01-01

    A case progressing from symptoms of conversion disorder to dissociative disorder and then to multiple personality disorder as per DSM-III-R criteria is being reported. The clinical implications are discussed.

  16. MULTIPLE PERSONALITY DISORDER FOLLOWING CONVERSION AND DISSOCIATIVE DISORDER NOS : A CASE REPORT

    OpenAIRE

    Jhingan, Harsh Prem; Aggarwal, Neeruj; Saxena, Shekhar; Gupta, Dhanesh K

    2000-01-01

    A case progressing from symptoms of conversion disorder to dissociative disorder and then to multiple personality disorder as per DSM-III-R criteria is being reported. The clinical implications are discussed.

  17. Multiple personality disorder following conversion and dissociative disorder nos : a case report.

    Science.gov (United States)

    Jhingan, H P; Aggarwal, N; Saxena, S; Gupta, D K

    2000-01-01

    A case progressing from symptoms of conversion disorder to dissociative disorder and then to multiple personality disorder as per DSM-III-R criteria is being reported. The clinical implications are discussed.

  18. Mimicry between mitochondrial disorder and multiple sclerosis.

    Science.gov (United States)

    Finsterer, Josef; Höftberger, Romana; Stöllberger, Claudia; Rolinski, Boris

    2012-06-01

    Under certain conditions or at certain stages of the disease course, multiple sclerosis (MS) and mitochondrial disorder (MID) may be differential diagnoses and thus may be confused with each other. In a 30 years old female MS was diagnosed at age 16 year upon recurrent sensory disturbances of the right lower leg, an "inflammatory" cerebrospinal fluid, and a cerebral MRI with multiple non-enhancing white matter lesions. Steroids were repeatedly given but because of rapid deterioration treatment was switched to interferon and mitoxantrone, without improvement. Fourteen years after onset the patient additionally presented with a history of rhabdomyolysis, hypothyroidism, ophthalmoparesis, anarthria, tetraspasticity, tetraparesis, and joint contractures. After MID had been diagnosed in her mother she was re-evaluated and elevated resting lactate, axonal polyneuropathy, and empty sella were additionally found. Muscle biopsy revealed myophagy, fat deposition, and type-II predominance, and biochemical investigations showed a deficiency of complex I and IV of the respiratory chain. MID was diagnosed also in the index patient. It is concluded that even if CSF investigations or imaging studies suggest MS, differentials such as MIDs need to be excluded before prescribing medication possibly toxic to a MID. An "inflammatory CSF" may also occur in MIDs.

  19. Imunofenotipagem e rearranjo gênico em doenças pulmonares linfocíticas e linfoproliferativas Immunophenotyping and gene rearrangement analysis in lymphoid/lymphoproliferative disorders of the lungs

    Directory of Open Access Journals (Sweden)

    Camila Cristina Ishikawa

    2007-12-01

    Full Text Available OBJETIVO: Determinar a utilidade, na prática rotineira, da análise da clonalidade dos linfócitos T e B nos tecidos pulmonares por reação em cadeia da polimerase no diagnóstico das doenças linfoproliferativas pulmonares. MÉTODOS: Avaliaram-se, mediante análise imunohistoquímica e rearranjo molecular dos genes, 8 casos de pneumonia intersticial linfocítica (PIL e 7 casos de doenças linfoproliferativas pulmonares. RESULTADOS: Todos os 8 casos de PIL expressaram imunocoloração moderada a forte para CD3, em contraste com apenas 2 casos de linfoma e 1 caso de pseudolinfoma. Rearranjo gênico foi detectado em 4 de 8 casos de PIL, o que mudou o diagnóstico de PIL para linfoma, indicando, assim, a importância da detecção de rearranjo gênico em casos de PIL. Nesta situação, rearranjo gênico usando-se os pares de primers VH/JH e Vgama11/Jgama12 foi detectado em 3 e 1 casos de PIL, respectivamente, e não foram detectadas anormalidades gênicas usando-se as pares Dbeta1/Jbeta2 e Vgama101/Jgama12. Uma associação positiva foi detectada entre a intensidade de imunoexpressão CD20 e CD68 e rearranjo gênico usando-se o par de primers VH/JH. Antes do rearranjo gênico, 4 pacientes com PIL morreram rapidamente, enquanto que, após o rearranjo gênico, apenas 1 paciente com PIL morreu. CONCLUSÕES: A detecção de células B e T monoclonais por imunofenotipagem e reação em cadeia da polimerase mostrou impacto no diagnóstico de linfomas pulmonares em pacientes previamente diagnosticados com PIL. Portanto, imunofenotipagem e reação em cadeia da polimerase devem ser incluídas como métodos de 'padrão ouro' na rotina diagnóstica.OBJECTIVE: To determine the usefulness, in routine practice, of using polymerase chain reaction to analyze B and T lymphocyte clonality in pulmonary tissue as a tool for the diagnosis of pulmonary lymphoproliferative disorders. METHODS: Immunohistochemistry and molecular gene rearrangement analysis were

  20. Dissociation in hypnosis and multiple personality disorder.

    Science.gov (United States)

    Bowers, K S

    1991-07-01

    The first part of this paper examines the concept of dissociation in the context of hypnosis. In particular, the neodissociative and social psychological models of hypnosis are compared. It is argued that the social psychological model, in describing hypnotic enactments as purposeful, does not adequately distinguish between behavior that is enacted "on purpose" and behavior that serves or achieves a purpose. 2 recent dissertations (Hughes, 1988; Miller, 1986) from the University of Waterloo are summarized, each of which supports the neodissociative view that hypnotic behavior can be purposeful (in the sense that the suggested state of affairs is achieved) and nonvolitional (in the sense that the suggested state of affairs is not achieved by high level executive initiative and ongoing effort). The second part of the paper employs a neodissociative view of hypnosis to help understand the current epidemic of multiple personality disorder (MPD). In particular, it is argued that many symptoms of MPD are implicitly suggested effects--particularly prone to occur in persons who have a lifelong tendency to use dissociative type defenses. The present author believes that this account is easier to sustain conceptually and empirically than the current view, which states that a secondary (tertiary, etc.) personality accounts for the striking phenomenological discontinuities experienced by MPD patients.

  1. Reflections on multiple personality disorder as a developmentally complex adaptation.

    Science.gov (United States)

    Armstrong, J G

    1994-01-01

    Recent advances in the understanding of multiple personality disorder provide the groundwork for its creative reconciliation with psychoanalysis. This paper uses psychoanalytic, modern developmental, and psychological assessment perspectives to conceptualize multiple personality disorder as a developmentally protective response to chronic childhood trauma. Implications of this theory for clinical work with these patients are discussed.

  2. Susceptibility-weighted imaging and diffusion-weighted imaging findings in central nervous system monomorphic B cell post-transplant lymphoproliferative disorder before and after treatment and comparison with primary B cell central nervous system lymphoma.

    Science.gov (United States)

    Ginat, Daniel Thomas; Purakal, Alixandra; Pytel, Peter

    2015-11-01

    The purpose of this article is to review the MRI features of monomorphic central nervous system post-transplant lymphoproliferative disorder (CNS PTLD), including diffusion-weighted and susceptibility-weighted sequences before and after treatment and to compare the imaging findings with those of primary central nervous system B cell lymphoma (PCNS BCL). Retrospective review of the brain MRI characteristics in patients with pathology proven monomorphic CNS PTLD and PCNS BCL was performed. In particular, the enhancement, diffusion-weighted, susceptibility-weighted MRI characteristics of the lesions were evaluated. In addition, the diffusion-weighted, susceptibility-weighted MRI features after treatment for CNS PTLD were evaluated. A total of 12 lesions in six patients with CNS PTLD and 12 lesions in nine patients with PCNS BCL were identified on MRI. Among the CNS PTLD lesions with post-contrast images, 80 % demonstrated peripheral enhancement. All of the CNS PTLD lesions contained foci of intratumoral susceptibility signal (ITSS) and the average mean ADC values and ratios were 0.892 × 10(-3) mm(2)/s (standard deviation: 0.082 × 10(-3) mm(2)/s) and 1.19 (standard deviation: 0.15), respectively. On the other hand, 75 % of the PCNS BCL displayed diffuse enhancement, two cases (16.7 %) contained ITSS, and the mean ADC values and ratios were 0.721 × 10(-3) mm(2)/s (standard deviation: 0.093 × 10(-3) mm(2)/s), and 0.99 (standard deviation: 0.17), respectively. Thus, the presence of heterogeneous lesions with ITSS that do not necessarily have as extensive restricted diffusion as PCNS BCL is suggestive of CNS PTLD in the appropriate clinical setting. The preliminary data in this series suggests that diffusion-weighted imaging may serve as a useful biomarker for monitoring treatment response, in which successful treatment of CNS PTLD may result in increased ADC values. In addition, foci of susceptibility effect in CNS PTLD tend to persist or increase over the course of

  3. 微小RNA223在B淋巴增殖性疾病中的表达及其临床意义%Expression of microRNA-223 and its clinical value in B lymphoproliferative disorders

    Institute of Scientific and Technical Information of China (English)

    周可树; 宋永平; 邱录贵; 于珍; 易树华; 李增军; 安刚; 王燕婴; 邹德慧; 齐军元; 赵耀中

    2011-01-01

    目的 检测微小RNA (microRNA) 223在我国常见B淋巴增殖性疾病中的表达并分析其临床意义。方法 2003至2010年中国医学科学院血液病医院慢性淋巴细胞白血病(CLL)53例,套细胞淋巴瘤(MCL) 13例,脾边缘区淋巴瘤(SMZL)9例,健康对照12名。取外周血(78例)或骨髓(9例),常规分离单个核细胞并行CD19磁珠分选。提取CD19+B淋巴细胞的总RNA,应用TaqMan 探针法检测microRNA-223的表达。收集患者临床资料,应用SPSS 16.0软件进行统计学分析。结果 (1) microRNA-223的表达在CLL、MCL及SMZL分别为:4.58±0.62、4.03±0.54、4.63±0.57,显著低于健康对照(5.69±0.60,P<0.01);microRNA-223在MCL的表达显著低于CLL及SMZL(P<0. 05),而其在CLL与SMZL之间表达差异无统计学意义(P>0.05);(2)CLL患者microRNA-223的表达随疾病进展下调;CLL中IgVH未突变患者microRNA-223的表达水平显著低于IgVH突变患者(4. 05±0.69比4.67±0.51,P=0. 003);microRNA-223在13q-阳性患者的表达显著高于13q-阴性患者(4. 76±0.45比4.25±0.67,P=0. 044);(3)根据IgVH突变状态采用受试者工作特征(ROG)曲线方法,将microRNA-223的表达分为阳性组及阴性组。microRNA-223阳性组患者的中位疾病无进展生存(PFS)时间为48个月,高于microRNA-223阴性组的9个月(P =0.001),microRNA-223阳性组患者截至随访结束,无一例死亡。结论 micmRNA-223可能在B淋巴增殖性疾病的发病中起重要作用;其与患者预后相关,可能是CLL新的较为可靠的预后指标。%Objective To detect the expression of microRNA-223 and analyze its clinical value in B lymphoproliferative disorders. Methods Peripheral blood samples ( n = 78) and bone marrow samples ( n =9 ) were collected from patients with chronic lymphocytic leukemia ( CLL, n = 53 ), mantle cell lymphoma ( MCL, n = 13 ), splenic marginal zone lymphoma ( SMZL, n = 9) and healthy donors ( n = 12) at

  4. Rapidly progressive post-transplant lymphoproliferative disease following withdrawal of sirolimus.

    Science.gov (United States)

    Mendelson, Marc; Barday, Zunaid; Eastman, Roland; Le Feuvre, David; Candy, Sally; Wu, Hue-Tsi; Swanepoel, Charles

    2012-08-24

    Sirolimus, a potent inhibitor of B- and T-cell activation. is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder following the withdrawal of sirolimus.

  5. X-Linked Lymphoproliferative Disease Presenting as Pancytopenia in a 10-Month-Old Boy

    Directory of Open Access Journals (Sweden)

    S. Nicole Chadha

    2010-01-01

    Full Text Available X-linked lymphoproliferative disease, also known as Duncan's syndrome, is a rare genetic disorder that causes exaggerated immune responses to Epstein-Barr virus (EBV infection and often leads to death. Patient presentation varies but can include signs and symptoms typical of EBV, pancytopenia, and fulminant hepatitis.

  6. Methylphenidate and Comorbid Anxiety Disorder in Children with both Chronic Multiple Tic Disorder and ADHD

    Science.gov (United States)

    Gadow, Kenneth D.; Nolan, Edith E.

    2011-01-01

    Objective: To determine if comorbid anxiety disorder is associated with differential response to immediate release methylphenidate (MPH-IR) in children with both ADHD and chronic multiple tic disorder (CMTD). Method: Children with (n = 17) and without (n = 37) diagnosed anxiety disorder (ANX) were evaluated in an 8-week, placebo-controlled trial…

  7. Case study: Malingering or multiple personality disorder?

    Directory of Open Access Journals (Sweden)

    Alba García-Cortés

    2017-03-01

    Full Text Available The dissociative identity disorder (DID can be considered a rare disorder because of its seemingly low prevalence. However, in recent years it points to the possible underdiagnosis because its complexity and confusion at the time of differential diagnosis. On the other hand, the malingering of mental psychopathology can have a major socio-economic and legal impact, particularly important in this type of disorder, given the inability it generates and its complex diagnostic. This paper refers the case of a patient admitted to the short-term hospitalization unit of Dr. Rodríguez Lafora Hospital (Madrid with depressive symptoms. Then the patient seemed to become a TID case. The evaluation consisted of a psychological history and the application of the Structured Inventory of Malingered Symptoms (SIMS and the Millon Clinical Multiaxial Inventory (MCMI-II. The results showed an altered personality profile as well as likely malingered symptoms, what prevented us from a DID diagnosis. In view of the results, possible implications of this case for the clinical setting are discussed.

  8. Immune Disorder HSCT Protocol

    Science.gov (United States)

    2016-11-01

    Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  9. A review of the dissociative disorders: from multiple personality disorder to the posttraumatic stress

    Directory of Open Access Journals (Sweden)

    Modesto J. Romero-López

    Full Text Available In this paper we review the idea of dissociation, dissociative disorders and their relationship with the processes of consciousness. We will deal specifically with multiple personality disorder and posttraumatic stress disorder. Both polarize the discussion of diagnostic categories with dissociative symptoms. This review compares the initial ideas (one century old with the current scenario and emerging trends in research, which are relating cognitive processes and dissociative phenomena and disorders from a neuroscientific approach. We discuss the ideas on dissociation, hypnosis and suicide associated with these disorders. There seems to be a lack of consensus as to the nature of dissociation with theoretical, empirical and clinical implications.

  10. Optimal Management of Autoimmune Lymphoproliferative Syndrome in Children.

    Science.gov (United States)

    George, Lindsey A; Teachey, David T

    2016-08-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte homeostasis, resulting from mutations in the Fas apoptotic pathway. Clinical manifestations include noninfectious and nonmalignant lymphadenopathy, splenomegaly, and autoimmune pathology-most commonly, autoimmune cytopenias. Rarely, and in association with specific genetic mutations, patients with ALPS may go on to develop secondary lymphoid malignancies. Though ALPS is a rare disorder, it should be suspected and ruled out in children presenting with chronic and refractory multilineage cytopenias associated with nonmalignant lymphoproliferation. Revised diagnostic criteria and insights into disease biology have improved both diagnosis and treatment. Sirolimus and mycophenolate mofetil are the best-studied and most effective corticosteroid-sparing therapies for ALPS, and they should be considered first-line therapy for patients who need chronic treatment. This review highlights practical clinical considerations for diagnosis and management of ALPS.

  11. [Affective and psychotic disorders in multiple sclerosis].

    Science.gov (United States)

    Pozuelo-Moyano, Beatriz; Benito-León, Julián

    2015-12-01

    Introduccion. La esclerosis multiple (EM) es la segunda causa mas importante de discapacidad de origen neurologico en los adultos jovenes. Tanto la sintomatologia fisica como la psiquiatrica (trastornos afectivos y psicoticos) impactan de manera negativa en la calidad de vida relacionada con la salud de los pacientes con EM. Objetivo. Elucidar de modo critico la prevalencia y la patogenia de los sintomas afectivos y psicoticos presentes en la EM. Desarrollo. Se incluye una actualizacion de los estudios publicados mas significativos que han analizado la prevalencia y la patogenia de la sintomatologia afectiva y psicotica en los pacientes con EM. Para explorar la asociacion entre los sintomas afectivos y psicoticos con la EM se ha revisado la evidencia disponible hasta el momento. Conclusiones. La depresion es el trastorno psiquiatrico mas frecuente en la EM. Es necesaria mas investigacion para elucidar los mecanismos subyacentes que pueden provocar sintomas afectivos y psicoticos en la EM. El control de dichos sintomas en los pacientes de EM podria mejorar su calidad de vida relacionada con la salud.

  12. The criminal responsibility of people with multiple personality disorder.

    Science.gov (United States)

    Saks, E

    1995-01-01

    Because multiple personality disorder (MPD) is more frequently diagnosed today than in the past, it is likely that more multiples will plead insanity. The courts are in a state of disarray as to how best to respond to these pleas. This article considers multiples' responsibility on three interpretations of the status of their alters: that they are different people; that they are different personalities; or that they are parts of one complex, deeply divided personality. On all three theories multiples are nonresponsible. Nevertheless, three rare circumstances exist under which multiples should be found guilty. The article concludes by indicating the kinds of issues psychiatry might explore to further assist the law in its analysis of the criminal responsibility of multiples.

  13. Multiple personality disorder and borderline personality disorder. Distinct entities or variations on a common theme?

    Science.gov (United States)

    Lauer, J; Black, D W; Keen, P

    1993-06-01

    We report data from a comparison of 14 subjects with multiple personality disorder (MPD) and 13 subjects with borderline personality disorder (BPD). There were few significant differences between the groups. The authors discuss the concept of MPD as an epiphenomenon of BPD, and argue their fundamental similarity.

  14. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

    NARCIS (Netherlands)

    R. Kyle (Robert); B.G.M. Durie (Brian); S.V. Rajkumar (Vincent); O. Landgren; J. Bladé (Joan); G. Merlini; N. Kröger; H. Einsele (Hermann); D. Vesole (David); M.A. Dimopoulos (Meletios); J.F. San Miguel (Jesús Fernando); H. Avet-Loiseau; R. Hajek (Roman); W. Chen (Wei); K.C. Anderson (Kenneth Carl); H. Ludwig (Heinz); P. Sonneveld (Pieter); S. Pavlovsky; A. Palumbo (Antonio); P.G. Richardson; B. Barlogie (Bart); P. Greipp (Philip); R. Vescio (Robert); I. Turesson; J. Westin (Johan); M. Boccadoro (Mario)

    2010-01-01

    textabstractMonoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is a

  15. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

    NARCIS (Netherlands)

    R. Kyle (Robert); B.G.M. Durie (Brian); S.V. Rajkumar (Vincent); O. Landgren; J. Bladé (Joan); G. Merlini; N. Kröger; H. Einsele (Hermann); D. Vesole (David); M.A. Dimopoulos (Meletios); J.F. San Miguel (Jesús Fernando); H. Avet-Loiseau; R. Hajek (Roman); W. Chen (Wei); K.C. Anderson (Kenneth Carl); H. Ludwig (Heinz); P. Sonneveld (Pieter); S. Pavlovsky; A. Palumbo (Antonio); P.G. Richardson; B. Barlogie (Bart); P. Greipp (Philip); R. Vescio (Robert); I. Turesson; J. Westin (Johan); M. Boccadoro (Mario)

    2010-01-01

    textabstractMonoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is a

  16. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

    NARCIS (Netherlands)

    R. Kyle (Robert); B.G.M. Durie (Brian); S.V. Rajkumar (Vincent); O. Landgren; J. Bladé (Joan); G. Merlini; N. Kröger; H. Einsele (Hermann); D. Vesole (David); M.A. Dimopoulos (Meletios); J.F. San Miguel (Jesús Fernando); H. Avet-Loiseau; R. Hajek (Roman); W. Chen (Wei); K.C. Anderson (Kenneth Carl); H. Ludwig (Heinz); P. Sonneveld (Pieter); S. Pavlovsky; A. Palumbo (Antonio); P.G. Richardson; B. Barlogie (Bart); P. Greipp (Philip); R. Vescio (Robert); I. Turesson; J. Westin (Johan); M. Boccadoro (Mario)

    2010-01-01

    textabstractMonoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is

  17. [Dispute over the multiple personality disorder: theoretical or practical dilemma?].

    Science.gov (United States)

    Stankiewicz, Sylwia; Golczyńska, Maria

    2006-01-01

    Dissociative identity disorder (DID) could also be referred to as multiple personality disorder (MPD). Due to rare occurrence and difficulty in its' identification it is infrequently diagnosed in Poland. The indicated disorder has been portrayed by the authors throughout the historical context, referring to initial 18th century's references concerning dissociation. A typical dissociatively disordered person has been characterized along with his individual personality categories such as: original personality, altered personality, host and personality fragment. Moreover various diagnosis criterions of DID have been introduced. DID has also been differentiated with other disorders: PTSD (post-traumatic stress disorder) and BPD (borderline personality disorder). A hypothesis has been set up, stating that DID is directly correlated with the trauma experienced during childhood, while PTSD is linked with traumatic lived-through events in the later period of ones' life. The most contemporary and frequently used research tools for DID have been indicated: dissociative experience scale (DES) and somatoform dissociation questionnaire (SDQ-20). Based upon the known literature, the authors have presented treatment methods such as hypnotherapy and recorded therapy sessions. It is the view of the authors that the switching in dissociative identity disorder is of adaptive character (it occurrs depending upon adaptive needs).

  18. Rapidly evolving hypopituitarism in a boy with multiple autoimmune disorders.

    Science.gov (United States)

    Jevalikar, Ganesh; Wong, Sze Choong; Zacharin, Margaret

    2013-09-01

    A 10-year-old boy with acute onset cranial diabetes insipidus and multiple autoimmune disorders had evolving panhypopituitarism, thought to be due to autoimmune hypophysitis. Over 18 months, a dramatic clinical course with progressive hypopituitarism and development of type 1 diabetes mellitus was evident. Serial brain imaging showed changes suggestive of germinoma.

  19. A More Unified View of the Multiple Personality Disorder.

    Science.gov (United States)

    Kelley, Ronald L.; Kodman, Frank

    1987-01-01

    Offers perspective of Multiple Personality Disorder (MPD) phenomenon based on current clinical experience. Asserts that the Jmind is polypsychic with multitude of psychological systems and processes existing in conjunction with one another, that MPD individuals have fragmented or dissociated ego states due to stress on unity of sense of self, and…

  20. Indicators of Multiple Personality Disorder for the Clinician.

    Science.gov (United States)

    Dalton, Thomas W.

    Multiple personality disorder (MPD) is now recognized as a valid diagnostic category. Occurrence may be higher than previously suspected. While physiological testing of MPD has shown significant differences between the various personalities of individuals in terms of galvanic skin response, electroencephalogram recordings, electrodermal response…

  1. A More Unified View of the Multiple Personality Disorder.

    Science.gov (United States)

    Kelley, Ronald L.; Kodman, Frank

    1987-01-01

    Offers perspective of Multiple Personality Disorder (MPD) phenomenon based on current clinical experience. Asserts that the Jmind is polypsychic with multitude of psychological systems and processes existing in conjunction with one another, that MPD individuals have fragmented or dissociated ego states due to stress on unity of sense of self, and…

  2. Indicators of Multiple Personality Disorder for the Clinician.

    Science.gov (United States)

    Dalton, Thomas W.

    Multiple personality disorder (MPD) is now recognized as a valid diagnostic category. Occurrence may be higher than previously suspected. While physiological testing of MPD has shown significant differences between the various personalities of individuals in terms of galvanic skin response, electroencephalogram recordings, electrodermal response…

  3. Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders.

    Science.gov (United States)

    Frederick, Meredith C; Cameron, Michelle H

    2016-03-01

    Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis.

  4. Treatment for multiple personality disorder: at what cost?

    Science.gov (United States)

    Piper, A

    1994-01-01

    The material presented in this paper suggests that before mental health practitioners ask of society the resources to treat those thousands of patients diagnosed with MPD in the past few years, a critical attempt should be made to evaluate the efficacy of the type of treatment currently recommended for the condition. Proponents of the disorder claim its treatment is cost-effective, but this article's analysis indicates that it is simply premature to make claims about the treatability or prognosis of multiple personality disorder.

  5. Prevalence and patterns of renal involvement in imaging of malignant lymphoproliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Bach, Andreas Gunter; Behrmann, Curd; Spielmann, Rolf Peter; Surov, Alexey (Dept. of Radiology, Martin-Luther-Univ. Halle-Wittenberg, Halle (Germany)), Email: andreas.bach@medizin.uni-halle.de; Holzhausen, Hans Jurgen (Dept. of Pathology, Martin-Luther-Univ. Halle-Wittenberg, Halle (Germany)); Katzer, Michaela (Dept. of Urology, Martin-Luther-Univ. Halle-Wittenberg, Halle (Germany)); Arnold, Dirk (Univ. Cancer Center Hamburg, Hamburg (Germany))

    2012-04-15

    Background: Renal involvement in patients with lymphoproliferative disease is an uncommon radiological finding. Purpose: To determine its prevalence and radiological appearances in a patient population. Material and Methods: All forms of lymphoproliferative disease (ICD: C81-C96) were considered. From January 2005 to January 2010, 668 consecutive patients with lymphoproliferative disease were identified with the help of the radiological database and patient records. Inclusion criteria were complete staging including appropriate CT scan and/or MRI. All stored images (initial staging and follow-up examinations) were reviewed. Results: Review of all stored images revealed renal infiltration in patients with non-Hodgkin lymphoma (11 of 364 = 3.0%; median age = 65 years, m:f = 6:5) but also multiple myeloma (2 of 162 = 1.2%; median age = 72 years; m:f = 1:1) and leukemia (5 of 101 4.9%; median age = 12 years; m:f = 2:3). There were no cases of renal infiltration in 41 patients with Hodgkin's disease. In total there were six patients with solitary lesions, five patients with diffuse renal enlargement, four patients with perirenal lesions, and two patients with direct invasion of the kidney. Conclusion: In leukemia the most common imaging pattern is diffuse enlargement. In the other subtypes of lymphoproliferative disease no specific correlation between typical CT patterns and subtype of lymphoproliferative disease can be found. The prevalence of renal involvement is in line with earlier studies. Contrary to earlier reports, multiple lesions were not found to be a common pattern

  6. Familial Lymphoproliferative Malignancies and Tandem Duplication of NF1 Gene

    Directory of Open Access Journals (Sweden)

    Gustavo Fernandes

    2014-01-01

    Full Text Available Background. Neurofibromatosis type 1 is a genetic disorder caused by loss-of-function mutations in a tumor suppressor gene (NF1 which codifies the protein neurofibromin. The frequent genetic alterations that modify neurofibromin function are deletions and insertions. Duplications are rare and phenotype in patients bearing duplication of NF1 gene is thought to be restricted to developmental abnormalities, with no reference to cancer susceptibility in these patients. We evaluated a patient who presented with few clinical signs of neurofibromatosis type 1 and a conspicuous personal and familiar history of different types of cancer, especially lymphoproliferative malignancies. The coding region of the NF-1 gene was analyzed by real-time polymerase chain reaction and direct sequencing. Multiplex ligation-dependent probe amplification was performed to detect the number of mutant copies. The NF1 gene analysis showed the following alterations: mosaic duplication of NF1, TRAF4, and MYO1D. Fluorescence in situ hybridization using probes (RP5-1002G3 and RP5-92689 flanking NF1 gene in 17q11.2 and CEP17 for 17q11.11.1 was performed. There were three signals (RP5-1002G3conRP5-92689 in the interphases analyzed and two signals (RP5-1002G3conRP5-92689 in 93% of cells. These findings show a tandem duplication of 17q11.2. Conclusion. The case suggests the possibility that NF1 gene duplication may be associated with a phenotype characterized by lymphoproliferative disorders.

  7. Adolescent multiple personality disorder: a preliminary study of eleven cases.

    Science.gov (United States)

    Dell, P F; Eisenhower, J W

    1990-05-01

    The diagnostic features and treatment histories of 11 adolescents with multiple personality disorder (MPD) are presented. Clinical evaluation revealed that the majority of these adolescents manifested extremely variable school performance, disruptive behavior, trances, amnesias, mood swings, sharp changes in personality, apparent lying, voices heard in the head, and depression. All had a history of childhood trauma: Sexual abuse (73%), physical abuse (73%), and emotional abuse (82%). Seventy-three percent had a parent with a diagnosable dissociative disorder; 36% of the mothers had MPD. These adolescents had a mean number of 24.1 alter personalities and appear to have become multiple at a mean age of 3 years, 1 month. All patients had angry protector alters, depressed alters, scared alters, and child alters. Fifty-four percent of these cases have integrated during treatment or are progressing toward integration. The remaining cases dropped out of therapy.

  8. Toward a psychoanalytic understanding of multiple personality disorder.

    Science.gov (United States)

    Reis, B E

    1993-01-01

    The author suggests a developmental psychoanalytic frame from which to understand the clinical phenomenology of multiple personality disorder (MPD). Annihilation anxiety and fears of nonbeing are understood as central; they are seen as resulting from actual early traumatic impingements at key developmental periods. Alter "personalities" are conceptualized as functional delusional processes that serve to maintain self-cohesion. The alters are brought about through the subject's lack of capacity for illusion. Some therapeutic implications regarding a psychoanalytic stance are discussed.

  9. Multiple personality disorder manifesting itself under the mask of transsexualism.

    Science.gov (United States)

    Modestin, J; Ebner, G

    1995-01-01

    The case of a young female patient is described who presented symptoms of transsexualism; surgical intervention was considered. Admitted to the hospital after having become depressed and suicidal, a thorough examination and observation revealed the presence of multiple personality disorder (MPD). Even though transsexualism and MPD represent two different conditions, there are many similarities between them. The possibility of MPD should be considered in every case of transsexualism.

  10. Unexplained lymphadenopathies: autoimmune lymphoproliferative syndrome in an adult patient.

    Science.gov (United States)

    Leal-Seabra, Fatima; Costa, Gonçalo Sarmento; Coelho, Henrique Pereira; Oliveira, Agripino

    2016-12-15

    Autoimmune lymphoproliferative syndrome (ALPS) is characterised by massive enlargement of the lymphoid organs, autoimmune cytopenias and a predisposition to develop lymphoid malignancies. The basic defect is a disturbance of the lymphocyte apoptosis, and a high number of circulating TCRab CD3(+)CD4(-)CD8(-) T-cells (double-negative T cells (DNT cells)). We describe a case of a 41-year-old man with fever, hepatosplenomegaly, multiple lymphadenopathy, autoimmune haemolytic anaemia and severe thrombocytopenia. Peripheral blood immunophenotyping revealed elevation of the characteristic DNT cells in 8% and high levels of interleukin 10. Histopathological analysis of lymph nodes showed lymphadenitis with paracortical hyperplasia. It was assumed as a probable diagnosis of ALPS, and the procedure was to medicate the patient with steroids. As a result, a significant clinical improvement was achieved, and he has been in remission for 2 years. To our knowledge, this is the first case reported in a Portuguese adult patient.

  11. Psychiatric disorders revealing multiple sclerosis after 20 years of evolvement

    Directory of Open Access Journals (Sweden)

    Aicha Slassi Sennou

    2014-01-01

    Full Text Available Previous research indicates that the onset of psychiatric disorders is sometimes associated with multiple sclerosis (MS evolving several years later. However, information on why this might occur, and on the outcomes of such patients, is still lacking. We aim to discuss these limitations with the current paper. We describe a 51-year-old female who demonstrated severe anxiety disorder and depression years before developing MS neurological symptoms. The patient was treated for these psychiatric disorders over 20 years. In the last 3 years of her treatment, the patient demonstrated a choreic-type of movement disorder in all her limbs. This disorder is consistent with relapsing-remitting MS. Clinical and magnetic resonance imaging (MRI examinations demonstrated aspects of MS, without MS being diagnosed conclusively. The visual evoked potential indicated a diagnosis of conduction abnormalities. The established diagnosis was slow relapsing MS. The patient underwent methylprednisolone bolus (1 g/day. This case-study suggests that health professionals should conduct a full neurological assessment when they find atypical psychiatric symptoms in a patient. This would make sure that patients receive a better standard of care, and thus experience a better quality of life.

  12. Anxiety Symptoms in Boys with Autism Spectrum Disorder, Attention-Deficit Hyperactivity Disorder, or Chronic Multiple Tic Disorder and Community Controls

    Science.gov (United States)

    Guttmann-Steinmetz, Sarit; Gadow, Kenneth D.; DeVincent, Carla J.; Crowell, Judy

    2010-01-01

    We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) in 5 groups of boys with neurobehavioral syndromes: attention-deficit/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD plus chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community Controls. Anxiety symptoms were…

  13. Anxiety Symptoms in Boys with Autism Spectrum Disorder, Attention-Deficit Hyperactivity Disorder, or Chronic Multiple Tic Disorder and Community Controls

    Science.gov (United States)

    Guttmann-Steinmetz, Sarit; Gadow, Kenneth D.; DeVincent, Carla J.; Crowell, Judy

    2010-01-01

    We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) in 5 groups of boys with neurobehavioral syndromes: attention-deficit/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD plus chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community Controls. Anxiety symptoms were…

  14. Bloom syndrome: multiple retinopathies in a chromosome breakage disorder.

    Science.gov (United States)

    Bhisitkul, R B; Rizen, M

    2004-03-01

    To describe multiple retinal abnormalities in a patient with Bloom syndrome, including early macular drusen, diabetic retinopathy, and the onset of leukaemic retinopathy. Clinical data were collected over 1 year of follow up, and ocular abnormalities in Bloom syndrome were reviewed from the literature. A 39 year old man with a rare autosomal recessive "chromosome breakage" syndrome was followed. A variety of ocular findings have been reported in Bloom syndrome; this patient had hard drusen in both maculae, non-proliferative diabetic retinopathy, and haemorrhagic retinopathy as a herald of acute lymphocytic leukaemia. Bloom syndrome is a rare disorder of genomic instability, in which a variety of ocular abnormalities have been found. Described here are multiple retinal manifestations arising from characteristic systemic associations of diabetes mellitus and leukaemia, as well as macular hard drusen.

  15. Prevalence of temporomandibular disorders symptoms in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Lucas S. C. Carvalho

    2014-06-01

    Full Text Available The aim of the present study was to assess the prevalence of symptoms of temporomandibular disorders (TMD in patients with the relapsing-remitting form of multiple sclerosis (MS, the relationship between TMD and the severity of MS, and the presence of TMD symptoms in the evaluated groups. Sixty individuals were evaluated: 30 patients diagnosed with relapsing-remitting MS and 30 control individuals matched for gender and age range with no neurologic pathology. In order to investigate the TMD symptoms, the questionnaires of the EACD (European Academy of Craniomandibular Disorders and the RDC/TMD (Research Diagnostic Criteria for Temporomandibular Disorders, both validated for TMD research, were administered. To assess the extent of disability produced by MS, the Expanded Disability Status Scale (EDSS was used. The prevalence of TMD symptoms in patients with MS was 56.7% versus 16.7% for the control group, with a statistically significant difference between the groups (p=0.0016. No correlation was found between the severity of MS and the prevalence of TMD symptoms (Fisher's test, p=1.0.

  16. Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis.

    Science.gov (United States)

    Weisfeld-Adams, James D; Katz Sand, Ilana B; Honce, Justin M; Lublin, Fred D

    2015-03-01

    Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient's 'multiple sclerosis-like' phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis.

  17. Can Multiple Sclerosis as a Cognitive Disorder Influence Patients’ Dreams?

    Directory of Open Access Journals (Sweden)

    Abdorreza Naser Moghadasi

    2013-04-01

    Full Text Available Dream should be considered as a kind of cognitive ability that is formed parallel to other cognitive capabilities like language. On the other hand, multiple sclerosis (MS is a complex disease that can involve different aspects of our cognition. Therefore, MS may influence patients’ dreams. In fact, we do not know what the importance of dream is in MS, but further studies may introduce dream and dreaming as a sign of improvement or progression in MS disease.Multiple sclerosis (MS is a disease that involves different areas of the brain and is accompanied by several disorders of the central nervous system. The topology of the disease and different areas of the brain that are involved during the disease may cause various changes in dreams, because dreaming has a close relation with the human brain physiology. The destruction of this physiology by a disease like MS with the ability of involving different areas of brain, may probably lead to changes in dreaming.This topic can also lead to a discussion from another point of view that is a different interpretation of these findings. By analyzing contents of hundreds of dreams, Domhoff concluded that the content of a dream is the continuance of our daily activities.1 In other words, the constitutive elements of our dreams are the ones that we think about and experience during a day. Strange and fantasy dreams constitute a very low percentage of the dreams and more than 70% of them are nothing but our daily activities in wakefulness.2Domhoff represents a kind of cognitive approach in the field of dream according to this considerable fact and also the evolution of dream’s content in children in accordance with their growth and changes of dream due to brain lesions. According to this approach, dream is also a kind of cognitive activity that is formed parallel to other cognitive capabilities like language. Moreover, whatever brings us various cognitive understandings such as hearing and seeing during

  18. Some aspects of balance disorder in patients with multiple sclerosis.

    Science.gov (United States)

    Burina, Adnan; Sinanović, Osman; Smajlović, Dzevdet; Vidović, Mirjana; Brkić, Fuad

    2008-02-01

    The aim of this study was to analyze: frequency of balance disorder (vertigo and disequilibrium), frequency of abnormalities in auditory evoked potentials (AEP) and magnetic resonance imaging (MRI) changes of the brain in multiple sclerosis (MS) patients with balance disorder, relation of patient's disability status to balance disorder and relation of the changes in MRI of the brainstem to AEP abnormalities. It was analyzed 60 patients with relapsing-remitting form of MS. Two groups of patients were made consecutively under Expanded Disability Status Scale score (EDSS): A (EDSS or =5,0). The study was retrospective-prospective. After the neurological exam AEP and MRI of the brain have been done. Balance disorder has been verified as initial symptom in 29 (48,4%) and out of them disequilibrium experienced 24 (83,4%) patients. During the relapses balance disorder experienced 48 (80%) patients and in 37 (77,1%) it was disequilibrium. Among them 33 (68,7%) were with lower EDSS ( or =5). There is no correlation between disability status and vertigo which means that vertigo is not more frequent in more disabled patients and vice-versa. The AEP were pathological in 57 (95%) patients. Of all 29 patients with vertigo AEP were pathological in 28 (96,5%) while in 31 patients without vertigo pathological AEP were in 29 (93,5%) but it is not statistical significant. The most frequent characteristic of AEP changes were prolonged inter-peak latency III-V waves (48 patients or 80%). The plaque in brainstem visualized by MRI was found in 41 (71,8%) of patients (38 or 92,6% of them had pathological AEP and in three patients AEP were normal). In group of patients with pathological AEP, 38 (66,6%) of them had plaque in brainstem. In other three patients with normal AEP it was visualized plaque in brainstem. In the group of 29 patients with balance disorder, 20 (68,9%) had plaque in brainstem as well as 21 (67,7%) out of 31 patients without balance disorder had plaque in the brainstem

  19. A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats.

    Science.gov (United States)

    Aberdein, Danielle; Munday, John S; Gandolfi, Barbara; Dittmer, Keren E; Malik, Richard; Garrick, Dorian J; Lyons, Leslie A

    2017-02-01

    British shorthair (BSH) kittens in multiple litters died as a result of a severe non-neoplastic lymphoproliferative disease that showed many similarities with human autoimmune lymphoproliferative syndrome (ALPS). Human ALPS is caused by inherited defects in FAS-mediated lymphocyte apoptosis and the possibility of similar defects was investigated in BSH cats. The whole genomes of two affected kittens were sequenced and compared to 82 existing cat genomes. Both BSH kittens had homozygous insertions of an adenine within exon 3 of the FAS-ligand gene. The resultant frameshift and premature stop codon were predicted to result in a severely truncated protein that is unlikely to be able to activate FAS. Three additional affected BSH kittens were homozygous for the variant, while 11 of 16 unaffected, but closely related, BSH cats were heterozygous for the variant. All BSH cats in the study were from a population with significant inbreeding. The variant was not identified in a further survey of 510 non-BSH cats. Identification of a genetic defect in the FAS-mediated apoptosis pathway confirms that the lymphoproliferative disease in BSH cats fulfills the diagnostic criteria for ALPS in humans. These results will enable the development of a genetic test to detect BSH carrier animals.

  20. Association of severe myoclonic epilepsy of infancy (SMEI with probable autoimmune lymphoproliferative syndrome-variant

    Directory of Open Access Journals (Sweden)

    A. Berio

    2014-12-01

    Full Text Available The paper reported on a case of severe myoclonic epilepsy of infancy (SMEI associated with a probable autoimmune lymphoproliferative syndrome variant (Dianzani autoimmune lymphoproliferative disease (DALD. A male patient with typical features of SMEI and a SCN1A gene variant presented in the first year of life with multiple lymph nodes, palpable liver at 2 cm from the costal margin, neutropenia, dysgammaglobulinemia, relative and sometimes absolute lymphocytosis. Subsequently the patient presented with constantly raised IgA in serum and positive antinuclear and thyroid antimicrosomal antibodies. The diagnosis of probable autoimmune lymphoproliferative syndrome was made; arthritis, skin and throat blisters, which appeared subsequently led to the diagnosis of linear IgA disease. On the basis of these unique associations, the Authors hypothesized that autoimmunity may be partly responsible of the severe epileptic symptomatology, perhaps mediated by autoantibodies against sodium channels or by accompanying cytotoxic T-lymphocytes. Corticosteroid treatment ameliorated the epilepsy and laboratory tests. Future studies will be necessary to evaluate the relevance of autoimmunity in SMEI.

  1. Case report of a person with Down's syndrome and multiple personality disorder.

    Science.gov (United States)

    Fotheringham, J B; Thompson, F

    1994-03-01

    A case is presented of an individual with Down's syndrome and multiple personality disorder. No such cases were found in a review of the literature. Three other individuals with Down's syndrome are also discussed whose symptoms range from experiencing imaginary friends to experiencing borderline multiple personality disorder. In all these cases the imaginary friends became more evident and resistive of diversion as the levels of stress increased. We speculate that experiencing imaginary friends progresses to experiencing multiple personality disorder in some individuals as personal stress increases. These cases also indicate that limited cognitive development does not preclude individuals from presenting with imaginary friends or multiple personality disorder.

  2. Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS).

    Science.gov (United States)

    Teachey, David T; Seif, Alix E; Grupp, Stephan A

    2010-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of T cell dysregulation caused by defective Fas-mediated apoptosis. Patients with ALPS can develop a myriad of clinical manifestations including lymphadenopathy, hepatosplenomegaly, autoimmunity and increased rates of malignancy. ALPS may be more common that originally thought, and testing for ALPS should be considered in patients with unexplained lymphadenopathy, hepatosplenomegaly, and/or autoimmunity. As the pathophysiology of ALPS is better characterized, a number of targeted therapies are in preclinical development and clinical trials with promising early results. This review describes the clinical and laboratory manifestations found in ALPS patients, as well as the molecular basis for the disease and new advances in treatment.

  3. Frequent hypermethylation of DBC1 in malignant lymphoproliferative neoplasms

    DEFF Research Database (Denmark)

    Grønbæk, Karin Elmegård; Ralfkiaer, U.; Dahl, C.

    2008-01-01

    follicular lymphomas, 5 of 5 mantle cell lymphomas, 4 of 4 small lymphocytic lymphomas, 1 of 2 lymphoplasmacytoid lymphomas, and in 12 of 12 acute lymphoblastic leukemias, but was unmethylated in 1 case of splenic marginal zone lymphoma, in 12 of 12 multiple myelomas, in 24 of 24 reactive lymph nodes......Allelic loss at chromosome 9q31-34 is a frequent event in many lymphoproliferative malignancies. Here, we examined DBC1 at 9q33.1 as a potential target in lymphomagenesis. DBC1 is a putative tumor suppressor that has been shown to be involved in the regulation of cell growth and programmed cell...... death. The methylation status of the DBC1 promoter CpG island was examined by methylation-specific PCR, bisulfite sequencing, and methylation-specific melting curve analysis. DBC1 was hypermethylated in 5 of 5 B-cell-derived lymphoma cell lines, 41 of 42 diffuse large B-cell lymphomas, 24 of 24...

  4. Bipolar Disorder and Multiple Sclerosis: A Case Series

    Directory of Open Access Journals (Sweden)

    Youssef Sidhom

    2014-01-01

    Full Text Available Background. The prevalence of psychiatric disturbance for patients with multiple sclerosis (MS is higher than that observed in other chronic health conditions. We report three cases of MS and bipolar disorder and we discuss the possible etiological hypothesis and treatment options. Observations. All patients fulfilled the McDonald criteria for MS. Two patients were followed up in psychiatry for manic or depressive symptoms before developing MS. A third patient was diagnosed with MS and developed deferred psychotic symptoms. Some clinical and radiological features are highlighted in our patients: one manic episode induced by high dose corticosteroids and one case of a new orbitofrontal MRI lesion concomitant with the emergence of psychiatric symptoms. All patients needed antipsychotic treatment with almost good tolerance for high dose corticosteroids and interferon beta treatment. Conclusions. MRI lesions suggest the possible implication of local MS-related brain damage in development of pure “psychiatric fits” in MS. Genetic susceptibility is another hypothesis for this association. We have noticed that interferon beta treatments were well tolerated while high dose corticosteroids may induce manic fits.

  5. Bedside Tested Ocular Motor Disorders in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    G. Servillo

    2014-01-01

    Full Text Available Background/Aims. Ocular motor disorders (OMDs are a common feature of multiple sclerosis (MS. In clinical practice, if not reported by patients, OMDs are often underdiagnosed and their prevalence is underestimated. Methods. We studied 163 patients (125 women, 76.7%, 38 men, 23.3%; median age 45.0 years; median disease duration 10 years; median EDSS 3.5 with definite MS (n=150, 92% or clinically isolated syndrome (n=13, 8% who underwent a thorough clinical examination of eye movements. Data on localization of previous relapses, MS subtype, and MRI findings were collected and analyzed. Results. Overall, 111/163 (68.1% patients showed at least one abnormality of eye movement. Most frequent OMDs were impaired smooth pursuit (42.3%, saccadic dysmetria (41.7%, unilateral internuclear ophthalmoplegia (14.7%, slowing of saccades (14.7%, skew deviation (13.5%, and gaze evoked nystagmus (13.5%. Patients with OMDs had more severe disability (P=0.0005 and showed more frequently infratentorial MRI lesions (P=0.004. Localization of previous relapses was not associated with presence of OMDs. Conclusion. OMDs are frequent in patients with stable (no relapses MS. A precise bedside examination of eye motility can disclose abnormalities that imply the presence of subclinical MS lesions and may have a substantial impact on definition of the diagnosis and on management of MS patients.

  6. Satanism, ritual abuse, and multiple personality disorder: a sociohistorical perspective.

    Science.gov (United States)

    Mulhern, S

    1994-10-01

    During the past decade in North America, a growing number of mental health professionals have reported that between 25% and 50% of their patients in treatment for multiple personality disorder (MPD) have recovered early childhood traumatic memories of ritual torture, incestuous rape, sexual debauchery, sacrificial murder, infanticide, and cannibalism perpetrated by members of clandestine satanic cults. Although hundreds of local and federal police investigations have failed to corroborate patients' therapeutically constructed accounts, because the satanic etiology of MPD is logically coherent with the neodissociative, traumatic theory of psychopathology, conspiracy theory has emerged as the nucleus of a consistent pattern of contemporary clinical interpretation. Resolutely logical and thoroughly operational, ultrascientific psychodemonology remains paradoxically oblivious to its own irrational premises. When the hermetic logic of conspiracy theory is stripped away by historical and socio/psychological analysis, however, the hypothetical perpetrators of satanic ritual abuse simply disappear, leaving in their wake the very real human suffering of all those who have been caught up in the social delusion.

  7. 流式细胞术检测异基因造血干细胞移植后多形性淋巴细胞增殖性疾病——附二例报告%Evaluation of polymorphic post-allotransplant lymphoproliferative disorder by flow cytometry

    Institute of Scientific and Technical Information of China (English)

    王卉; 童春容; 王静波; 林跃辉; 张帅; 李燕燕; 康蕊; 蔡鹏

    2010-01-01

    Objective To study the role of flow cytometry (FCM) in detection of polymorphic posttransplant lymphoproliferative disorders(PTLD).Methods and Results Two patients presented with fever and multiple lymphadenopathy on day 46 and day 50 respectively after successful allogeneic hematopoietic stem cell transplantation(allo-HSCT).The symptoms couldn't be controlled by antibiotics.The pelymorphic PTLD was diagnosed based on the elevation of bone marrow EB virus DNA and detection of subsets of light chain restricted B cells and/or plasma cells in peripheral blood(PB) samples.The lymphocyte immunophenotypes from PB and/or bone marrow(BM) samples were serially tested by FCM after lowering the dose of immunosupressive agents and treating with antivirus drugs,anti-CD20 antibodies,and cytotoxic T cell infusion.B cells were undetable in two patient,but monoclonal plasma cells appeared or maintained.One patient died after two weeks.Another patient was still on treatment.B cells and plasms cells couldn't be detected in her PB,but there were monoclonal plasma cells in her BM.FCM have a prominent advantage in detect polymorphic PTLD,since it can effectively recognize different cell groups in blood and identify monoclonal subsets.Besides,the immunophenotype of plasma cells in polymorphic PTLD might be different from that in typical plasma cell myeloma.Conclusion Polymorphic PTLD can be detected and followed up by FCM.BM is more suitable than PB for monitoing the disease.Besides lymph node biopsy,B cell abnormaliity could be detected in PB in allo-HSCT patients.%目的 研究流式细胞术检测在异基因造血干细胞移植(allo-HSCT)后多形性淋巴细胞增殖性疾病诊断中的作用.方法 采用多色流式细胞术诊断allo-HSCT后多形性淋巴细胞增殖性疾病.结果 2例ailo-HSCT患者分别于移植后46 d(+46 d)和+50 d出现高热,多处淋巴结肿大,抗炎治疗无效,骨髓EB病毒DNA水平升高,经流式细胞术检测发现外周血多群轻链限

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

    OpenAIRE

    Oliveira, Joao B.; 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.; Rao, V. Koneti

    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 esta...

  9. Four cases of supposed multiple personality disorder: evidence of unjustified diagnoses.

    Science.gov (United States)

    Freeland, A; Manchanda, R; Chiu, S; Sharma, V; Merskey, H

    1993-05-01

    Four cases are presented in which an unjustified diagnosis of multiple personality disorder was made. These cases are used to illustrate the concern that some cases of multiple personality disorder may be the result of misdiagnosis by both patients and clinicians.

  10. Comparative Study of Children with ADHD Only, Autism Spectrum Disorder + ADHD, and Chronic Multiple Tic Disorder + ADHD

    Science.gov (United States)

    Gadow, Kenneth D.; DeVincent, Carla J.; Schneider, Jayne

    2009-01-01

    Objective: Identification of differences among children with ADHD only, autism spectrum disorder (ASD)+ADHD, and chronic multiple tic disorder (CMTD)+ADHD may lead to better understanding of clinical phenotypes. Method: Children were evaluated using the parent- and teacher-completed questionnaires. Results: All three groups were highly similar in…

  11. Longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders

    NARCIS (Netherlands)

    Dijkstra-Kersten, Sandra M. A.; Sitnikova, Kate; Terluin, Berend; Penninx, Brenda W. J. H.; Twisk, Jos W. R.; van Marwijk, Harm W. J.; van der Horst, Henriette E.; van der Wouden, Johannes C.

    Objective: To examine longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. Methods: Follow-up data of 584 participants with remitted depressive or anxiety disorders were used from the Netherlands Study of Depressive and Anxiety disorders.

  12. A systematic review of the incidence and prevalence of sleep disorders and seizure disorders in multiple sclerosis

    DEFF Research Database (Denmark)

    Marrie, Ruth Ann; Reider, Nadia; Cohen, Jeffrey

    2015-01-01

    BACKGROUND: Several studies have suggested that comorbid neurologic disorders are more common than expected in multiple sclerosis (MS). OBJECTIVE: To estimate the incidence and prevalence of comorbid seizure disorders and sleep disorders in persons with MS and to evaluate the quality of studies...... included studies qualitatively and quantitatively (I² statistic), and conducted meta-analyses among population-based studies. RESULTS: We reviewed 32 studies regarding seizure disorders. Among population-based studies the incidence of seizure disorders was 2.28% (95% CI: 1.11-3.44%), while the prevalence...... was 3.09% (95% CI: 2.01-4.16%). For sleep disorders we evaluated 18 studies; none were population-based. The prevalence ranged from 0-1.6% for narcolepsy, 14.4-57.5% for restless legs syndrome, 2.22-3.2% for REM behavior disorder, and 7.14-58.1% for obstructive sleep apnea. CONCLUSION: This review...

  13. Atypical presentation of autoimmune lymphoproliferative syndrome due to CASP10 mutation.

    Science.gov (United States)

    Tripodi, Serena Ilaria; Mazza, Cinzia; Moratto, Daniele; Ramenghi, Ugo; Caorsi, Roberta; Gattorno, Marco; Badolato, Raffaele

    2016-09-01

    Herein we describe the case of a 8-years-old boy with diagnosis of atypical autoimmune lymphoproliferative syndrome (ALPS), carrying heterozygous mutation of CASP10 gene (I406L). He presented with multiple non-invasive infections of the skin, that were associated to chronic non-malignant non-infectious lymphadenopathy, failure to thrive, weakness, arthralgia, relapsing oral aftosis, and expansion of TCRαβ(+) CD4(-)/CD8(-) T cells. This observation suggests that cutaneous infections can be observed in ALPS patients carrying CASP10 mutations.

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

    Science.gov (United States)

    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...

  15. Small-Sized Clone of T Cells in Multiple Myeloma Patient after Auto-SCT: T-LGL Leukemia Type or Clonal T-Cell Aberration?

    OpenAIRE

    Giuseppe Mele; Marilena Greco; Maria Rosaria Coppi; Giacomo Loseto; Angela Melpignano; Salvatore Mauro; Gianni Quarta

    2013-01-01

    Second cancers and particularly postransplant lymphoproliferative disorders (PTLDs) are extremely rare in patients undergoing autologous peripheral blood stem cell transplantation (auto-SCT). We report the case of clonally rearranged T-cell expansion which occurred after auto-SCT for Multiple Myeloma (MM). Does asymptomatic clonal T-cell large granular lymphocytic proliferation, in our experience, represent either a secondary cancer after auto-SCT or clonal T cell aberration or derive from ex...

  16. Child Abuse and Multiple Personality Disorders: Review of the Literature and Suggestions for Treatment.

    Science.gov (United States)

    Coons, Philip M.

    1986-01-01

    Multiple personality disorder is associated with a high incidence of physical and sexual abuse during childhood. While difficult to diagnose, multiple personality is easier to treat if diagnosed early in childhood or adolescence. Treatment for multiple personality focuses on establishing trust and communicating with and integrating the…

  17. Child Abuse and Multiple Personality Disorders: Review of the Literature and Suggestions for Treatment.

    Science.gov (United States)

    Coons, Philip M.

    1986-01-01

    Multiple personality disorder is associated with a high incidence of physical and sexual abuse during childhood. While difficult to diagnose, multiple personality is easier to treat if diagnosed early in childhood or adolescence. Treatment for multiple personality focuses on establishing trust and communicating with and integrating the…

  18. Sensory and sensorimotor gating in children with multiple complex developmental disorders (MCDD) and autism

    DEFF Research Database (Denmark)

    Oranje, Bob; Lahuis, Bertine; van Engeland, Herman

    2013-01-01

    Multiple Complex Developmental Disorder (MCDD) is a well-defined and validated behavioral subtype of autism with a proposed elevated risk of developing a schizophrenic spectrum disorder. The current study investigated whether children with MCDD show the same deficits in sensory gating that are co......Multiple Complex Developmental Disorder (MCDD) is a well-defined and validated behavioral subtype of autism with a proposed elevated risk of developing a schizophrenic spectrum disorder. The current study investigated whether children with MCDD show the same deficits in sensory gating...

  19. Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation

    DEFF Research Database (Denmark)

    Thrane, Jens F; Sunde, Niels A; Bergholt, Bo

    2014-01-01

    Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation......Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation...

  20. Bone marrow findings in autoimmune lymphoproliferative syndrome with germline FAS mutation

    Science.gov (United States)

    Xie, Yi; Pittaluga, Stefania; Price, Susan; Raffeld, Mark; Hahn, Jamie; Jaffe, Elaine S.; Rao, V. Koneti; Maric, Irina

    2017-01-01

    Autoimmune lymphoproliferative syndrome is a rare genetic disorder characterized by defective FAS-mediated apoptosis, autoimmune disease, accumulation of mature T-cell receptor alpha/beta positive, CD4 and CD8 double-negative T cells and increased risk of lymphoma. Despite frequent hematologic abnormalities, literature is scarce regarding the bone marrow pathology in autoimmune lymphoproliferative syndrome. We retrospectively reviewed 3l bone marrow biopsies from a cohort of 240 patients with germline FAS mutations. All biopsies were performed for the evaluation of cytopenias or to rule out lymphoma. Clinical information was collected and morphological, immunohistochemical, flow cytometric and molecular studies were performed. Bone marrow lymphocytosis was the predominant feature, present in 74% (23/31) of biopsies. The lymphoid cells showed several different patterns of infiltration, most often forming aggregates comprising T cells in 15 cases, B cells in one and a mixture of T and B cells in the other seven cases. Double-negative T cells were detected by immunohistochemistry in the minority of cases (10/31; 32%); significantly, all but one of these cases had prominent double-negative T-lymphoid aggregates, which in four cases diffusely replaced the marrow space. One case showed features of Rosai-Dorfman disease, containing scattered S-100+ cells with emperipolesis and double-negative T cells. No clonal B or T cells were detected by polymerase chain reaction in any evaluated cases. Classical Hodgkin lymphoma was identified in three cases. Our results demonstrate that infiltrates of T cells, or rarely B cells, can be extensive in patients with autoimmune lymphoproliferative syndrome, mimicking lymphoma. A multi-modality approach, integrating clinical, histological, immunohistochemical as well as other ancillary tests, can help avoid this diagnostic pitfall. This study is registered at Clinicaltrials.gov ID # NCT00001350 PMID:27846610

  1. Autoimmune Lymphoproliferative Syndrome (ALPS) in a Boy with Massive Lymphadenopathy.

    Science.gov (United States)

    Kianifar, Hamid Reza; Khalesi, Maryam; Farid, Reza; Badiee, Zahra; Rastin, Maryam; Ahanchian, Hamid

    2010-09-01

    Autoimmune lymphoproliferative syndrome (ALPS) is an uncommon nonmalignant lymphoproliferative disease which is characterized by chronic, persistent or recurrent lymphadenopathy, splenomegaly, hepatomegaly, immune cytopenia , hypergammaglobinemia and increased risk of lymphoma. We report a 2-year old boy with hepatosplenomegaly as first presentation. Petechial and purpuric rashes with massive cervical lymphadenopathies developed 10 months later.In laboratory tests anemia, thrombocytopenia and hypergammaglobinemia were observed. According to flocytometry increased double negative T cells and by apoptosis assay decrease apoptosis of lymphocytes accompanied clinical manifestations, thus diagnosis of ALPS was established. In conclusion; in all patients with massive lymphadenopathy and hepatosplenomegay; especially with cytopenia; ALPS should be considered.

  2. The Parental Fitness of Mothers with Multiple Personality Disorder: A Preliminary Study.

    Science.gov (United States)

    Kluft, Richard P.

    1987-01-01

    A review of the parenting patterns of 75 mothers with multiple personality disorders indicated 38.7% were competent or exceptional mothers, 16% were grossly abusive, and 45.3% were compromised or impaired as parents. (DB)

  3. The Parental Fitness of Mothers with Multiple Personality Disorder: A Preliminary Study.

    Science.gov (United States)

    Kluft, Richard P.

    1987-01-01

    A review of the parenting patterns of 75 mothers with multiple personality disorders indicated 38.7% were competent or exceptional mothers, 16% were grossly abusive, and 45.3% were compromised or impaired as parents. (DB)

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. From Single to Multiple Deficit Models of Developmental Disorders

    Science.gov (United States)

    Pennington, Bruce F.

    2006-01-01

    The emerging etiological model for developmental disorders, like dyslexia, is probabilistic and multifactorial while the prevailing cognitive model has been deterministic and often focused on a single cognitive cause, such as a phonological deficit as the cause of dyslexia. So there is a potential contradiction in our explanatory frameworks for…

  6. Cataplexy and the switch process of multiple personality disorder.

    Science.gov (United States)

    La Via, M C; Brewerton, T D

    1996-07-31

    A case history is presented of an 18-year-old male with dissociative disorder and polysubstance abuse. The patient was observed to switch between three personalities, and the personality changes were often associated with symptoms of cataplexy. Both dissociative episodes and cataplexy are associated with strong affective stimuli. Similar reports in the literature are briefly reviewed.

  7. Transgenic mouse model of IgM+ lymphoproliferative disease mimicking Waldenström macroglobulinemia

    Science.gov (United States)

    Tompkins, V S; Sompallae, R; Rosean, T R; Walsh, S; Acevedo, M; Kovalchuk, A L; Han, S-S; Jing, X; Holman, C; Rehg, J E; Herms, S; Sunderland, J S; Morse, H C; Janz, S

    2016-01-01

    Waldenström macroglobulinemia (WM) is a low-grade incurable immunoglobulin M+ (IgM+) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM. To evaluate this possibility, we generated compound transgenic BALB/c mice that harbored the human BCL2 and IL6 transgenes, EμSV-BCL2-22 and H2-Ld-hIL6, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. We designated these mice BCL2+IL6+AID− and found that they developed—with full genetic penetrance (100% incidence) and suitably short latency (93 days median survival)—a severe IgM+ lymphoproliferative disorder that recapitulated important features of human WM. However, the BCL2+IL6+AID− model also exhibited shortcomings, such as low serum IgM levels and histopathological changes not seen in patients with WM, collectively indicating that further refinements of the model are required to achieve better correlations with disease characteristics of WM. PMID:27813533

  8. Treatment for a child with EBV-associated T/natural killer-cell lymphoproliferative disorder by hematopoietic stem cell transplantation%造血干细胞移植治疗儿童EB病毒相关T/NK细胞淋巴组织增殖性疾病疗效分析

    Institute of Scientific and Technical Information of China (English)

    吴南海; 龚小军; 栾佐; 王凯; 唐湘凤

    2012-01-01

    Objective To explore the therapeutic effect of hematopoietic stem cell transplantation for treatment of EBV-associated T/Natural Killer-cell Lymphoproliferative disorder in children. Methods A 13.5-year old boy .diagnosed with EBV-associated T/natural killer-cell lymphoproliferative disorder (EBV-T/NK-LPD) , received HLA-matched sibling PBSCT from his younger sister, as his disease was persistent after treatment with anti-virus drugs, EBV-CTL,interleukin-2 and chemotherapy. The conditioning regimen was TBI/CY+VP16 (total-body irradiation, 12 Gy in 8 fractions, -8d -5d; cyclophosphamide, 60mg/kgxtwo doses, -3d ~ -2d; a single dose of etoposide, 30mg/kg, -4d). The infused PBSCs contained 6.34×107kg nucleated cells and 3.80×106/ kg CD34 positive cells. GVHD prophylaxis consisted of cyclosporine A (CsA) and a short course of methotrexate (sMTX). Results The hematologic recovery was favorable. The patient achieved neutrophil engraftment at day +16;platelet engraftment was achieved at day +37;his hemo-gram completely recovered at day +60. The patient had no severe complications, such as fatal infections, hemorrhagic cystitis, veno-occlusive disease (VOD), interstitial pneumonia (IP),eytomegalovirus (CMV) infection, et al. He developed cutaneous Grade II acute graft-versus-host disease (GVHD) at day +62. The EBV-DNA was 1.2×105 copies/ml before transplant,and changed-over to negative at day +14; after this, the EBV-DNA was monitored weekly,persistently negative. After transplantation, the patient' s jaundice disappeared, and the liver function normalized. Rechecking type-B ultrasonic on the cervix and the abdomen, there was no signs of lymphadenectasis at pars cervicalis, hepatomega- ly , or splenomegaly; the previous lymphadenectasis at porta hepatic and aside abdominal aorta disappeared. Computed tomography scan at thorax dis- played no lymphadenectasis at portopulmonary, the mediastinum was normal. Up to now, and the patient has been followed up for 18 months after

  9. Quantitative monitoring of mononucleated cell Epstein-Barr virus (EBV)-DNA for predicting EBV associated lymphoproliferative disorders after stem cell transplantation%造血干细胞移植后单个核细胞EBV-DNA定量监测预测移植后淋巴增殖性疾病

    Institute of Scientific and Technical Information of China (English)

    王莉红; 李渊; 董玉君; 尹玥; 梁赜隐; 任汉云; 孙玉华; 邱志祥; 岑溪南; 欧晋平; 许蔚林; 王茫桔; 王文生

    2010-01-01

    目的 应用定量PCR方法 监测造血干细胞移植(HSCT)后单个核细胞EBV含量,评估其临床效果.方法 51例HSCT患者从预处理阶段开始,采用荧光定量PCR方法 每周1次检测外周s血单个核细胞EBV-DNA拷贝数,分析EBV再活化的影响因素以及EBV-DNA拷贝数与发生淋巴增殖性疾病(PTLD)的相关性.结果 51例患者EBV血症累积发生率为58.8%,HSCT后EBV感染的时间晚于CMV感染[分别为(39.6±23.5)d和(25.0±15.1)d,P<0.01].Allo-HSCT中HLA不合患者EBV血症的累积发生率显著高于HLA相合患者(分别为93.3%和48.1%,P<0.01),应用ATG组显著高于无ATG组(分别为92.3%和18.7%,P<0.01),年龄<20岁组患者显著高于≥20岁组(分别为100%和53.1%,P<0.01).30例患者中4例(13.3%)EBV血症发展为EBV-PTLD,均为持续2周以上EBV-DNA>106拷贝/ml的患者(13例中4例).PTLD患者的中位生存时间为19.5(11~75)d.结论 HSCT后EBV活化比率高,尤其是在HLA不相合供者、应用ATG和年龄<20岁的患者,有必要常规进行单个核细胞EBV-DNA检测.Allo-HSCT患者在EBV-DNA拷贝数>106拷贝/ml,尤其是持续2周以上者,易进展为PTLD,应给予抢先治疗.%Objective To monitor blood cells EBV-DNA copies by quantitative Epstein-Barr virus (EBV) polymerase chain reaction after hematopeietic stem cell transplantation (HSCT) and to evaluate its implication.Methods EBV-DNA copies of peripheral blood mononucleated cells (PBMNCs) were detected by fluorescence quantitative PCR once a week since conditioning regimen from fifty one patients received HSCT.Correlation between development of lymphoproliferative disorders (LPD) and EBV-DNA copies and influence factors of EBV reactivation were analyzed.Results The cumulative incidence of EBV viremia was 58.8%.EBV reactivation occurred (39.6±23.5) days after HSCT,later than that of cytnmegalovirus (CMV) reactivation (25.0±15.1) days (P<0.01).HLA mismatch (P<0.01),use of antithymocyte globulin (ATG) (P<0

  10. Multiple personality disorder in an intellectually disabled man: a case report.

    Science.gov (United States)

    Fairley, M; Jones, R C; McGuire, B E; Stevenson, J

    1995-03-01

    The case of a young man with the dual diagnoses of severe intellectual handicap (IQ 30 and mental age 4 years) and Multiple Personality Disorder is presented. The intellectual handicap is probably due to hypoxia in infancy and the Multiple Personality Disorder follows prolonged physical and sexual abuse. The patient frequently switches between any of nine discrete but incompletely formed identities. Although some personalities seem more capable than others, all have similar levels of disability on testing. The diagnosis of psychiatric disorders coexistent with the intellectual handicap is hindered by the difficulty in separating psychiatric phenomena from the behavioural disturbances associated with the disability. Differential diagnosis and management are discussed.

  11. Longitudinal prediction of disruptive behavior disorders in adolescent males from multiple risk domains.

    Science.gov (United States)

    Trentacosta, Christopher J; Hyde, Luke W; Goodlett, Benjamin D; Shaw, Daniel S

    2013-08-01

    The disruptive behavior disorders are among the most prevalent youth psychiatric disorders, and they predict numerous problematic outcomes in adulthood. This study examined multiple domains of risk during early childhood and early adolescence as longitudinal predictors of disruptive behavior disorder diagnoses among adolescent males. Early adolescent risks in the domains of sociodemographic factors, the caregiving context, and youth attributes were examined as mediators of associations between early childhood risks and disruptive behavior disorder diagnoses. Participants were 309 males from a longitudinal study of low-income mothers and their sons. Caregiving and youth risk during early adolescence each predicted the likelihood of receiving a disruptive behavior disorder diagnosis. Furthermore, sociodemographic and caregiving risk during early childhood were indirectly associated with disruptive behavior disorder diagnoses via their association with early adolescent risk. The findings suggest that preventive interventions targeting risk across domains may reduce the prevalence of disruptive behavior disorders.

  12. The incidence and prevalence of psychiatric disorders in multiple sclerosis

    DEFF Research Database (Denmark)

    Marrie, Ruth Ann; Reingold, Stephen; Cohen, Jeffrey

    2015-01-01

    -based studies, the prevalence of anxiety was 21.9% (95% CI: 8.76%-35.0%), while it was 14.8% for alcohol abuse, 5.83% for bipolar disorder, 23.7% (95% CI: 17.4%-30.0%) for depression, 2.5% for substance abuse, and 4.3% (95% CI: 0%-10.3%) for psychosis. CONCLUSION: This review confirms that psychiatric...... disorders in MS and evaluate the quality of included studies. METHODS: We searched the PubMed, PsychInfo, SCOPUS, and Web of Knowledge databases and reference lists of retrieved articles. Abstracts were screened for relevance by two independent reviewers, followed by full-text review. Data were abstracted...... comorbidity, particularly depression and anxiety, is common in MS. However, the incidence of psychiatric comorbidity remains understudied. Future comparisons across studies would be enhanced by developing a consistent approach to measuring psychiatric comorbidity, and reporting of age-, sex-, and ethnicity...

  13. Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative disorders

    NARCIS (Netherlands)

    Fossati, S; Boneschi, [No Value; Ferrucci, S; Brambilla, L

    1999-01-01

    BACKGROUND. The concomitant occurrence of more than one primary neoplasm in the same individual has led researchers to seek possible common etiopathogenetic factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and perhaps viral etiology. Four forms of KS are known: classic or M

  14. Post-transplant lymphoproliferative disorder following kidney transplantation

    DEFF Research Database (Denmark)

    Maksten, Eva Futtrup; Vase, Maja Ølholm; Kampmann, Jan;

    2016-01-01

    to identify possible PTLDs. Candidate PTLDs underwent histopathological review and classification. Seventy PTLD cases were identified in 2175 transplantations (3.2%). The incidence rate (IR) after first transplantation was 5.4 cases per 1000 patient-years (95% CI: 4.0-7.3). Most PTLDs were monomorphic (58...

  15. An Alternative Approach to the Effects of Multiple Traumas: Complex Post-Traumatic Stress Disorder.

    Science.gov (United States)

    Taycan, Okan; Yildirim, Ahmet

    2015-09-01

    Exposure to multiple traumatic events, particularly in childhood, has been shown to result in more complex symptoms than those seen after exposure to a single traumatic event. In case of overlooking the link between trauma and psychopathology, patients with multiple traumatic experiences receive a variety of different diagnoses that are unable to completely cover the clinical picture. Misdiagnoses of genuine cases inevitably lead to mistreatment. A diagnosis of complex post-traumatic stress disorder has been proposed to cover the emerging psychopathology in survivors of multiple traumas. This present report aimed to discuss the construct and to increase the awareness of complex post-traumatic stress disorder diagnosis among mental health professionals.

  16. Multiple immune disorders in unrecognized celiac disease: a case report

    Institute of Scientific and Technical Information of China (English)

    Giorgio La Villa; Peietro Pantaleo; Roberto Tarquini; Lino Cirami; Federico Perfetto; Francesco Mancuso; Giacomo Laffi

    2003-01-01

    We reported a female patient with unrecognized celiac disease and multiple extra intestinal manifestations, mainly related to a deranged immune function, including macroamilasemia, macrolipasemia, IgA nephropathy,thyroiditis, and anti-b2-glicoprotein-1 antibodies, that disappeared or improved after the implementation of a gluten-free diet.

  17. Multiple DSM-5 substance use disorders: A national study of US adults.

    Science.gov (United States)

    McCabe, Sean Esteban; West, Brady T; Jutkiewicz, Emily M; Boyd, Carol J

    2017-09-01

    Our aim is to determine the lifetime and past-year prevalence estimates of multiple Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) substance use disorders (SUDs) among U.S. adults. The 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions featured in-person interviews with a nationally representative sample of adults aged 18 and older. The majority of past-year nonalcohol DSM-5 SUDs had at least 1 other co-occurring past-year SUD, ranging from 56.8% (SE = 3.4) for past-year prescription opioid use disorder to 97.5% (SE = 2.7) for past-year hallucinogen use disorder. In contrast, only 15.0% (SE = 0.6) of past-year alcohol use disorders had a co-occurring past-year SUD. The odds of past-year multiple SUDs were greater among males, younger adults, African-Americans, and those with mood, personality, posttraumatic stress, or multiple psychiatric disorders. Assessment, diagnosis, and treatment often focus on individual substance-specific SUDs rather than multiple SUDs, despite evidence for substantial rates of polysubstance use in clinical and epidemiological studies. There are notable differences in the prevalence of multiple SUDs between alcohol use disorders and other nonalcohol SUDs that have important clinical implications; for example, multiple SUDs are more persistent than individual SUDs. These findings suggest that clinical assessment and diagnosis should screen for multiple SUDs, especially among adults with nonalcohol DSM-5 SUDs. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Delusional disorder and schizophrenia: a comparative study across multiple domains.

    Science.gov (United States)

    Peralta, V; Cuesta, M J

    2016-10-01

    Delusional disorder (DD) is an under-researched condition and its relationship to schizophrenia (SZ) controversial. This study aimed to further characterize DD and to examine multi-domain evidence for the distinction between DD and SZ. Using univariate analyses we examined 146 subjects with DD, 114 subjects with paranoid SZ and 244 subjects with non-paranoid SZ on 52 characteristics from several domains including demographics, risk factors, premorbid features, illness characteristics, index episode features, delusional-related features, response to treatment and outcome. In a further step, we searched for independent associations of the examined characteristics with DD v. SZ. Univariate analyses showed that DD differed from either form of SZ in 40 characteristics, the pattern of findings indicated that paranoid SZ was much more similar to non-paranoid SZ than DD. Relative to subjects with SZ, those with DD were more likely to have drug abuse before illness onset, better premorbid sexual adjustment, later age at illness onset, higher levels of affective symptoms and lack of insight, poorer response to antipsychotic medication, better functioning in the domains of personal care, paid work and social functioning; last, subjects with DD had fewer but more severe delusions and higher ratings of conviction of delusional experience than those with SZ. Predominance of jealousy and somatic delusions was confined to subjects with DD. DD and SZ represent two distinct classes of disorders, the differential features of DD being of nosological, aetiological and therapeutic relevance.

  19. A controlled study of formal thought disorder in children with autism and multiple complex developmental disorders.

    NARCIS (Netherlands)

    Gaag, R.J. van der; Caplan, R.; Engeland, H. van; Loman, F.

    2005-01-01

    Along with well-defined categories in classification systems (e.g., autistic disorders and attention-deficit/hyperactivity disorder (ADHD)), practitioners are confronted with many children showing mixed forms of developmental psychopathology. These clusters of symptoms are on the borderlines of more

  20. Multiple personality disorder and iatrogenesis: the cautionary tale of Anna O.

    Science.gov (United States)

    Weissberg, M

    1993-01-01

    An examination of Breuer's treatment of Anna O. illustrates some of the controversies surrounding the recent rise of case reports of multiple personality disorder. Anna O., the first patient of the cathartic method, psychoanalysis, and dynamic psychiatry, fits current criteria for multiple personality disorder. Breuer's treatment, however, may have contributed to her states of absence; the timing, type, and intensity of Breuer's interventions make it possible that he unwittingly encouraged and amplified Anna's dissociations, reified her ego fragments, and then explained Anna's symptoms with the pseudomemories and confabulations recovered from Anna while she was hypnotized. A review of Breuer's treatment highlights some of the controversial aspects of multiple personality disorder, specifically its possible vulnerability to iatrogenesis via suggestion and unconscious collusion and other factors. The current stance of some multiple personality disorder enthusiasts, opaque to their participation in interactions that may lead to certain patient productions, resembles the older psychoanalytic stance exemplified by the early Breuer and Freud. The dialectic of the therapist as a neutral observer versus as an influential participant continues to be a focus of controversy, both within psychoanalysis and psychotherapy and in the understandings of the etiology and treatment of multiple personality disorder.

  1. Nature and Specificity of Gestural Disorder in Children with Developmental Coordination Disorder: A Multiple Case Study

    Directory of Open Access Journals (Sweden)

    Orianne Costini

    2017-07-01

    Full Text Available Aim: Praxis assessment in children with developmental coordination disorder (DCD is usually based on tests of adult apraxia, by comparing across types of gestures and input modalities. However, the cognitive models of adult praxis processing are rarely used in a comprehensive and critical interpretation. These models generally involve two systems: a conceptual system and a production system. Heterogeneity of deficits is consistently reported in DCD, involving other cognitive skills such as executive or visual-perceptual and visuospatial functions. Surprisingly, few researches examined the impact of these functions in gestural production. Our study aimed at discussing the nature and specificity of the gestural deficit in DCD using a multiple case study approach.Method: Tasks were selected and adapted from protocols proposed in adult apraxia, in order to enable a comprehensive assessment of gestures. This included conceptual tasks (knowledge about tool functions and actions; recognition of gestures, representational (transitive, intransitive, and non-representational gestures (imitation of meaningless postures. We realized an additional assessment of constructional abilities and other cognitive domains (executive functions, visual-perceptual and visuospatial functions. Data from 27 patients diagnosed with DCD were collected. Neuropsychological profiles were classified using an inferential clinical analysis based on the modified t-test, by comparison with 100 typically developing children divided into five age groups (from 7 to 13 years old.Results: Among the 27 DCD patients, we first classified profiles that are characterized by impairment in tasks assessing perceptual visual or visuospatial skills (n = 8. Patients with a weakness in executive functions (n = 6 were then identified, followed by those with an impaired performance in conceptual knowledge tasks (n = 4. Among the nine remaining patients, six could be classified as having a visual

  2. Laminopathies: Multiple disorders arising from defects in nuclear architecture

    Indian Academy of Sciences (India)

    Veena K Parnaik; Kaliyaperumal Manju

    2006-09-01

    Lamins are the major structural proteins of the nucleus in an animal cell. In addition to being essential for nuclear integrity and assembly, lamins are involved in the organization of nuclear processes such as DNA replication, transcription and repair. Mutations in the human lamin A gene lead to highly debilitating genetic disorders that primarily affect muscle, adipose, bone or neuronal tissues and also cause premature ageing syndromes. Mutant lamins alter nuclear integrity and hinder signalling pathways involved in muscle differentiation and adipocyte differentiation, suggesting tissue-specific roles for lamins. Furthermore, cells expressing mutant lamins are impaired in their response to DNA damaging agents. Recent reports indicate that certain lamin mutations act in a dominant negative manner to cause nuclear defects and cellular toxicity, and suggest a possible role for aberrant lamins in normal ageing processes.

  3. Ethnopharmacological evaluation of Cenchrus ciliaris for multiple gastrointestinal disorders

    Directory of Open Access Journals (Sweden)

    Ambreen Aleem

    2017-06-01

    Full Text Available This study was conducted to rationalize the traditional uses of Cenchrus ciliaris in gastrointestinal disorders using in vivo and ex vivo assays. The antidiarrheal effect was evaluated in rats by the castor oil-induced diarrheal model. C. ciliaris (100, 300 and 500 mg/kg reduced the castor oil-induced diarrhea significantly. Another study carried out in mice to determine the intestinal transit rate showed that C. ciliaris (100 and 200 mg/kg inhibited the transit rate significantly. Ex vivo assay demonstrated that C. ciliaris (0.01–1 mg/mL relaxed the spontaneous and K+ (80 mM-induced contractions, like verapamil. The crude extract (75, 100 and 150 mg/kg also exhibited significant anti-emetic activity in chicks. These results indicate the presence of antispasmodic, antidiarrheal and antiemetic activities in C. ciliaris, thus providing the scientific basis for its traditional uses.

  4. Distinguishing between multiple personality disorder (dissociative identity disorder) and schizophrenia using the Structured Clinical Interview for DSM-IV Dissociative Disorders.

    Science.gov (United States)

    Steinberg, M; Cicchetti, D; Buchanan, J; Rakfeldt, J; Rounsaville, B

    1994-09-01

    The authors describe the systematic assessment of dissociative symptoms using the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) in 50 psychiatric outpatients with a referring DSM-III-R diagnosis of either schizophrenia or schizoaffective disorder (N = 31) and subjects with multiple personality disorder (MPD [DSM-IV name change: dissociative identity disorder]; N = 19). Results indicate that patients with MPD experience significantly higher scores for five specific dissociative symptoms than patients with schizophrenia or schizoaffective disorder. The range, severity, and nature of the five dissociative symptom areas evaluated by the SCID-D distinguish MPD from the occasional occurrence of dissociative symptoms which may be seen in schizophrenia. Systematic assessment of dissociative symptoms using the SCID-D can assist in accurate differential diagnosis of MPD and schizophrenia.

  5. Multiple Cavitating Nodules in a Renal Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Sharla-Rae J Olsen

    2009-01-01

    Full Text Available Pulmonary nodules are common following solid organ transplantation and vary in etiology. Nodules with central cavitation are most likely to be of infectious origin in the post-transplant population. A novel presentation of post-transplant lymphoproliferative disorder manifesting as multiple cavitating pulmonary nodules is described. The patient, a 45-year-old female renal transplant recipient, presented with constitutional symptoms and a chest x-ray showing multiple bilateral cavitating lesions. A computed tomography scan confirmed innumerable, randomly dispersed, cavitating nodules in the lung parenchyma. Multiple large hypodense lesions were identified in the liver and spleen. The appearance of the native and transplanted kidneys was normal. A liver biopsy identified an Epstein-Barr virus-negative, diffuse, large B cell lymphoma. Repeat imaging after treatment with a cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone/prednisolone regimen demonstrated dramatic resolution of all lesions. The present case represents a unique radiographic presentation of post-transplant lymphoproliferative disorder not previously reported in the literature.

  6. Autoimmune lymphoproliferative syndrome (ALPS). Case report and family history.

    Science.gov (United States)

    Ries, F; Ferster, A; Rieux-Laucat, F; Biwer, A; Dicato, M

    2010-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease caused by defective lymphocyte apoptosis and is characterized by non-malignant lymphoproliferation, hepatosplenomegaly, autoimmune manifestations and increased risk of both Hodgkin's and non-Hodgkin's lymphoma. Most forms of the disease are due to germ line mutations of the FAS gene and manifest during the first years of life with fluctuating lymphadenopathies, hemolysis, immune thrombocytopenia. During the second decade of life disease manifestations improve spontaneously but autoimmune problems still occur and there is an increased risk of lymphoproliferative malignancy. We describe a typical case of ALPS in a now 44 year old man, followed since the age of 2 for disease manifestations that were unclear at the beginning.

  7. Learning from extremism in the history of mental health. The example of multiple personality disorder.

    Science.gov (United States)

    Mohr, Wanda K

    2002-05-01

    This article reviews some of the history of the cultural forces that shaped the diagnosis of multiple personality disorder/dissociative identity disorder and the subsequent abuses that occurred at the time of its popularization. Some of the implications that can be drawn from these kinds of historical excesses in the field of mental health will be discussed. The article concludes by underscoring the ethical obligation inherent in maintaining healthy professional skepticism toward ideas driven by ideology and fad, rather than scientific empiricism.

  8. The effects of a multiple family therapy on adolescents with eating disorders: an outcome study.

    Science.gov (United States)

    Gelin, Zoé; Fuso, Silvana; Hendrick, Stephan; Cook-Darzens, Solange; Simon, Yves

    2015-03-01

    Multiple Family Therapy (MFT) has gained increasing popularity in the treatment of eating disorders and many programs have been developed over the past decade. Still, there is little evidence in the literature on the effectiveness on MFT for treating eating disorders. The present study examines the effects of a particular model of Multiple Family Therapy on eating disorder symptoms, quality of life, and percentage of Expected Body Weight (%EBW) in adolescents with eating disorders (ED). Eighty-two adolescents with ED, aged between 11 and 19 years, were assessed before and after treatment using the Eating Disorders Inventory 2 (EDI-2), the Outcome Questionnaire 45 (OQ-45) and %EBW. Results showed a significant increase in %EBW between the beginning and end of treatment, with a large effect size. 52.4% of patients achieved an EBW above 85%. Symptoms relative to all EDI dimensions (except for bulimia) significantly decreased during treatment. The three dimensions related to quality of life assessment also improved over the course of MFT. At the end of treatment, 70.7% of patients had a total OQ-45 score below clinical significance. This study suggests that Multiple Family Therapy may benefit adolescents with eating disorders, with improvement on several outcome measures (%EBW, ED symptoms, and quality of life). However, the lack of a comparison group entails caution when drawing conclusions. © 2014 Family Process Institute.

  9. Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Ji-Young [Department of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 150-950 (Korea, Republic of); Cha, Eun Suk; Lee, Jee Eun [Department of Radiology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of); Sung, Sun Hee [Department of Pathology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of)

    2013-07-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.

  10. Use of Sirolimus (Rapamycin) for Treatment of Cytopenias and Lymphoproliferation Linked to Autoimmune Lymphoproliferative Syndrome (ALPS). Two Case Reports.

    Science.gov (United States)

    Cayrol, Julie; Garrido Colino, Carmen

    2017-02-23

    Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis. Children present with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and autoimmune cytopenias. Recent advances show efficacy of treatment with immunosuppressive drugs. Sirolimus, an mammalian target of rapamycin inhibitor, improves autoimmune cytopenias and lymphoproliferation, with a safe profile. We present 2 patients, a 5-year-old girl and 15-year-old boy, diagnosed with ALPS with initial partial response to steroid treatment. Autoimmune cytopenias and lymphoproliferation then became refractory to treatment, with recurrence of symptoms. In both cases, treatment with sirolimus was started, with a rapid response, complete remission of cytopenias, and resolution of lymphoproliferation, with no significant adverse effects.

  11. Disorder chaos and multiple valleys in spin glasses

    CERN Document Server

    Chatterjee, Sourav

    2009-01-01

    We prove that the Sherrington-Kirkpatrick model of spin glasses is chaotic under small perturbations of the couplings at any temperature in the absence of an external field. The result is proved for two kinds of perturbations: (a) distorting the couplings via Ornstein-Uhlenbeck flows, and (b) replacing a small fraction of the couplings by independent copies. We further prove that the S-K model exhibits multiple valleys in its energy landscape, i.e. there are many states with near-minimal energy that are mutually nearly orthogonal. We show that the variance of the free energy of the S-K model is unusually small at any temperature. (By `unusually small' we mean that it is much smaller than the number of sites; in other words, it beats the classical Gaussian concentration inequality, a phenomenon that we call `superconcentration'.) We prove that the bond overlap in the Edwards-Anderson model of spin glasses is not chaotic under perturbations of the couplings, even large perturbations. Lastly, we obtain sharp low...

  12. The epigenetics of multiple sclerosis and other related disorders.

    Science.gov (United States)

    van den Elsen, Peter J; van Eggermond, Marja C J A; Puentes, Fabiola; van der Valk, Paul; Baker, David; Amor, Sandra

    2014-03-01

    Multiple Sclerosis (MS) is a demyelinating disease characterized by chronic inflammation of the central nervous system (CNS) gray and white matter. Although the cause of MS is unknown, it is widely appreciated that innate and adaptive immune processes contribute to its pathogenesis. These include microglia/macrophage activation, pro-inflammatory T-cell (Th1) responses and humoral responses. Additionally, there is evidence indicating that MS has a neurodegenerative component since neuronal and axonal loss occurs even in the absence of overt inflammation. These aspects also form the rationale for clinical management of the disease. However, the currently available therapies to control the disease are only partially effective at best indicating that more effective therapeutic solutions are urgently needed. It is appreciated that in the immune-driven and neurodegenerative processes MS-specific deregulation of gene expressions and resulting protein dysfunction are thought to play a central role. These deviations in gene expression patterns contribute to the inflammatory response in the CNS, and to neuronal or axonal loss. Epigenetic mechanisms control transcription of most, if not all genes, in nucleated cells including cells of the CNS and in haematopoietic cells. MS-specific alterations in epigenetic regulation of gene expression may therefore lie at the heart of the deregulation of gene expression in MS. As such, epigenetic mechanisms most likely play an important role in disease pathogenesis. In this review we discuss a role for MS-specific deregulation of epigenetic features that control gene expression in the CNS and in the periphery. Furthermore, we discuss the application of small molecule inhibitors that target the epigenetic machinery to ameliorate disease in experimental animal models, indicating that such approaches may be applicable to MS patients.

  13. Immunoglobulin G4-positive multi-organ lymphoproliferative syndrome with antiphospholipid antibody syndrome.

    Science.gov (United States)

    Kawakami, Nobuyo; Kawai, Kazuhiro; Baba, Naoko; Ohshima, Kouichi; Kanekura, Takuro

    2012-07-01

    We report immunoglobulin (Ig)G4-positive multi-organ lymphoproliferative syndrome (IgG4(+) -MOLPS) with antiphospholipid antibody syndrome (APS) in a 56-year-old Japanese man presenting with purpuric patches on his legs. Skin biopsy revealed leukocytoclastic vasculitis. Laboratory tests demonstrated high levels of serum IgG and IgG4, hypocomplementemia and anticardiolipin antibody. Echography of the lower limbs and pulmonary scintigraphy showed a thrombus in the left soleal vein and multiple emboli in the basal part of both inferior pulmonary arteries. Computed tomography revealed systemic lymphadenopathy. Histologically, there was reactive paracortical hyperplasia with proliferation of histiocytes and infiltration of IgG4-positive plasma cells. We made a diagnosis of IgG4(+) -MOLPS with APS. To our knowledge, this complication has not been reported previously.

  14. Marital and Family Therapy in the Treatment of Multiple Personality Disorder.

    Science.gov (United States)

    Sachs, Roberta G.; And Others

    1988-01-01

    Explores marital and family therapy in treatment of Multiple Personality Disorder (MPD), discussing role of family of origin in MPD development and role of nuclear family in its perpetuation. Suggests family and marital interventions, illustrating them with case examples. Proposes involving MPD client in marital or family therapy, in addition to…

  15. Outpatient Art Therapy with Multiple Personality Disorder: A Survey of Current Practice.

    Science.gov (United States)

    Mills, Anne

    1995-01-01

    Reports findings of a 1993 questionnaire completed by 46 North American art therapists that focuses on the outpatient treatment of multiple personality disorder. Includes information on role in diagnosing, fees and third-party payment, and therapeutic activities. Treatment issues include pacing and containment, and managing the client's chronic…

  16. Childhood Trauma and Multiple Personality Disorder: The Case of a 9-Year-Old Girl.

    Science.gov (United States)

    LaPorta, Lauren D.

    1992-01-01

    This paper reports the case of a nine-year-old female victim of sexual abuse, evaluated and diagnosed with multiple personality disorder over a six-month period. Included is a description of the child's presentation with historical and developmental data. A discussion of the dynamic and predisposing features of the case follows, along with…

  17. Hitting Closer to Home: A Multiple Family Prevention Group for Adolescent Disordered Eating

    Science.gov (United States)

    Clemency, Colleen E.; Rayle, Andrea Dixon

    2006-01-01

    This article presents an innovative multiple family psychoeducational group for the prevention of disordered eating among adolescent females. An overview of the concerns facing adolescents today is presented, including sociocultural norms, body dissatisfaction associated with pubertal changes, teasing regarding weight and shape, and family…

  18. Childhood Trauma and Multiple Personality Disorder: The Case of a 9-Year-Old Girl.

    Science.gov (United States)

    LaPorta, Lauren D.

    1992-01-01

    This paper reports the case of a nine-year-old female victim of sexual abuse, evaluated and diagnosed with multiple personality disorder over a six-month period. Included is a description of the child's presentation with historical and developmental data. A discussion of the dynamic and predisposing features of the case follows, along with…

  19. Outpatient Art Therapy with Multiple Personality Disorder: A Survey of Current Practice.

    Science.gov (United States)

    Mills, Anne

    1995-01-01

    Reports findings of a 1993 questionnaire completed by 46 North American art therapists that focuses on the outpatient treatment of multiple personality disorder. Includes information on role in diagnosing, fees and third-party payment, and therapeutic activities. Treatment issues include pacing and containment, and managing the client's chronic…

  20. Marital and Family Therapy in the Treatment of Multiple Personality Disorder.

    Science.gov (United States)

    Sachs, Roberta G.; And Others

    1988-01-01

    Explores marital and family therapy in treatment of Multiple Personality Disorder (MPD), discussing role of family of origin in MPD development and role of nuclear family in its perpetuation. Suggests family and marital interventions, illustrating them with case examples. Proposes involving MPD client in marital or family therapy, in addition to…

  1. Prevalence and classification of hallucinations in multiple sensory modalities in schizophrenia spectrum disorders

    NARCIS (Netherlands)

    Lim, Anastasia; Hoek, Hans W.; Deen, Mathijs L.; Blom, Jan Dirk

    2016-01-01

    Background: Auditory hallucinations are experienced by 60-80% of all patients diagnosed with a schizophrenia spectrum disorder. However, in this patient group, the prevalence of hallucinations in multiple sensory modalities, i.e. multimodal hallucinations (MMHs), is unknown. Aims: To assess the

  2. Prevalence and classification of hallucinations in multiple sensory modalities in schizophrenia spectrum disorders

    NARCIS (Netherlands)

    Lim, Anastasia; Hoek, Hans W.; Deen, Mathijs L.; Blom, Jan Dirk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Kahn, René S.; Meijer, Carin J.; Myin-Germeys, Inez; van Os, Jim; Wiersma, Durk

    2016-01-01

    Background Auditory hallucinations are experienced by 60–80% of all patients diagnosed with a schizophrenia spectrum disorder. However, in this patient group, the prevalence of hallucinations in multiple sensory modalities, i.e. multimodal hallucinations (MMHs), is unknown. Aims To assess the

  3. Soliton pulse propagation in the presence of disorder-induced multiple scattering in photonic crystal waveguides

    CERN Document Server

    Mann, Nishan

    2016-01-01

    We introduce a new coupled mode theory to model nonlinear Schr\\"{o}dinger equations for contra-propagating Bloch modes that include disorder-induced multiple scattering effects on nonlinear soliton propagation in photonic crystal waveguides. We also derive sub unit-cell coupling coefficients and use these to introduce a generalized length scale associated with each coupling effect. In particular, we define a multiple-scattering length scale that quantifies the spatial extent of a disorder-induced cavity mode. Our numerical simulations of nonlinear pulse propagation are in excellent qualitative agreement with recent experiments and provide insight into how disorder inhibits soliton propagation and other nonlinear propagation effects in photonic crystal waveguides.

  4. Rethinking the comparison of borderline personality disorder and multiple personality disorder.

    Science.gov (United States)

    Marmer, S S; Fink, D

    1994-12-01

    This article has made a number of points that assert what is today a minority position within the fields of MPD/DID and BPD. We hope our views will stimulate attempts by others to rethink their positions and test our assertions, so that issues surrounding these two disorders can be sharpened. For the sake of the clarity of future work, we summarize in outline form the essence of our viewpoint. 1. BPD and MPD/DID have similar appearing symptoms, such as identity problems, unstable affect modulation, self-destructive behaviors, chaotic impulse control, and troubled interpersonal relationships, but they have decisive differences in underlying dynamics, process, and structure. 2. DSM tends to blur these two disorders by its emphasis on phenomenology over inner structure, thus fostering misleading conclusions when DSM criteria are used to test for comorbidity or overlap between BPD and MPD/DID. 3. BPD and MPD/DID are both described dynamically as using the defense of splitting, but we contend that the splitting in each disorder is fundamentally different from the splitting in the other. BPD uses a polarization form of splitting, whereas MPD/DID uses ego splitting or identity division. 4. Both disorders partake in the process of dissociation, but the quality of dissociation in BPD is a "low-tech" spaced out type, whereas that of MPD/DID is a "high-tech" waking dream. 5. BPD structure is also "low tech," with polarization of self, object, and relationship. MPD/DID structure is "high tech," with heavily symbolic, highly nuanced variations of self, object, and relationship. 6. Although both conditions have etiologic elements of trauma, BPD has a larger degree of developmental deficiency, with a failure to complete the task of entering a repression hierarchy of defenses. MPD/DID, by use of primary process-linked symbolic dissociation, is able to continue development to the repression hierarchy, although at a profound cost of simultaneous suspension of reality testing. BPD

  5. Confirmation of childhood abuse in child and adolescent cases of multiple personality disorder and dissociative disorder not otherwise specified.

    Science.gov (United States)

    Coons, P M

    1994-08-01

    The diagnostic validity of multiple personality disorder (MPD) and its association to trauma have been questioned because corroboration of child abuse in studies of patients with MPD is scant. The purpose of this study was to determine on a retrospective basis whether external corroboration of child abuse could be found in a group of patients with MPD and dissociative disorder not otherwise specified. A group of child and adolescent psychiatric inpatients and outpatients was chosen because of the extensive number of collateral records collected on them in a tertiary care setting. This group was also chosen because of the intense interest paid by child protective services and courts to child abuse during the past 15 years. This retrospective chart review confirmed child abuse in eight of nine patients with MPD and in all 12 cases of dissociative disorder not otherwise specified. This study provides further evidence of the association of severe dissociative disorders with trauma, particularly child abuse. Future studies should be prospective and blinded to avoid the possibility of investigator bias, and should include a control group for comparison of base rate of child abuse.

  6. Schema therapy for personality disorders in older adults: a multiple-baseline study.

    Science.gov (United States)

    Videler, Arjan C; van Alphen, Sebastiaan P J; van Royen, Rita J J; van der Feltz-Cornelis, Christina M; Rossi, Gina; Arntz, Arnoud

    2017-04-21

    No studies have been conducted yet into the effectiveness of treatment of personality disorders in later life. This study is a first test of the effectiveness of schema therapy for personality disorders in older adults. Multiple-baseline design with eight cluster C personality disorder patients, with a mean age of   69. After a baseline phase with random length, schema therapy was given during the first year, followed by follow-up sessions during six months. Participants weekly rated the credibility of dysfunctional core beliefs. Symptomatic distress, early maladaptive schemas, quality of life and target complaints were assessed every six months and personality disorder diagnosis was assessed before baseline and after follow-up. Data were analyzed with mixed regression analyses. Results revealed significant linear trends during treatment phases, but not during baseline and follow-up. The scores during follow-up remained stable and were significantly lower compared to baseline, with high effect sizes. Seven participants remitted from their personality disorder diagnosis. Schema therapy appears an effective treatment for cluster C personality disorders in older adults. This finding is highly innovative as this is the first study exploring the effectiveness of psychotherapy, in this case schema therapy, for personality disorders in older adults.

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

    Science.gov (United States)

    The eight cases described herein represent the first reports of lymphoproliferative disease virus (LPDV) infection in wild turkeys and the first identification of LPDV in North America. Systemic lymphoproliferative disease was presumably the cause of morbidity and mortality in five of the eight turk...

  8. [Immunoglobulin G4-associated to multiorganic lymphoproliferative disease].

    Science.gov (United States)

    Bourlon, María T; Chapa, Mónica; Chablé Montero, Fredy; Hernández Calleros, Jorge

    2011-01-01

    We report a case of a woman with lymphoproliferative multiorganic immunoglobulin G4 (IgG4) related disease with extensive involvement showing dacryoadenitis, sialoadenitis, parotiditis, pancreatitis, pneumonitis, lymphadenopathy and immune thrombocytopenic purpura. Serum elevation of acute phase reactant, polyclonal hypergammaglobulinemia, positivity for antinuclear antibodies and rheumatoid factor was found. Hystologically plasma cell infiltration was demonstrated on glandular and lymphatic tissue and immunochemistry was positive for IgG4 in > 30%. Immunosuppressive treatment with steroids and azathioprine was given with an excellent clinical response, the marked radiologic evidence of improvement and the decrease in inflammatory makers that conducted to symptom remission are shown in the text.

  9. Systems of Selves: the Construction of Meaning in Multiple Personality Disorder

    Science.gov (United States)

    Hughes, Dureen Jean

    Current models for understanding both Multiple Personality Disorder and human mentation in general are both linear in nature and self-perpetuating insofar as most research in this area has been informed and shaped by extant psychological concepts, paradigms and methods. The research for this dissertation made use of anthropological concepts and methods in an attempt to gain a richer understanding of both multiple personality and fundamental universal processes of the mind. Intensive fieldwork using in-depth, open-ended interviewing techniques was conducted with people diagnosed with Multiple Personality Disorder with the purpose of mapping their personality systems in order to discover the nature of the relationships between the various alternate personalities and subsystems comprising the overall personality systems. These data were then analyzed in terms of dynamical systems theory ("Chaos Theory") as a way of understanding various phenomena of multiple personality disorder as well as the overall structure of each system. It was found that the application of the formal characteristics of nonlinear models and equations to multiple personality systems provided a number of new perspectives on mental phenomena. The underlying organizational structure of multiple personality systems can be understood as a phenomenon of spontaneous self-organization in far-from -equilibrium states which characterizes dissipative structures. Chaos Theory allows the perspective that the nature of the process of the self and the nature of relationship are one and the same, and that both can be conceived as ideas in struggle at a fractal boundary. Further, such application makes it possible to postulate an iterative process which would have as one of its consequences the formation of a processural self who is conscious of self as separate self. Finally, given that the iterative application of a few simple rules (or instructions) can result in complex systems, an attempt was made to discern

  10. [Multiple personality disorder. Presentation of 2 cases and a model of the etiology].

    Science.gov (United States)

    Pfeifer, S; Brenner, L; Spengler, W

    1994-09-01

    Although the syndrome of Multiple Personality Disorder (MPD) has received much interest in the international literature, there have been virtually no professional articles on the topic in German over the last 70 years. This is a report on two cases with nine and 70 persons respectively. Both had undergone severe and prolonged sexual abuse in childhood. Compared with DSM-III-R, the ICD-10 criteria seem to reflect historic reports on alternating personalities rather than recent empirical research on multiple personality. The proposed etiological model postulates that extreme trauma in childhood can result in dissociative vulnerability persisting into adulthood.

  11. Experience of gratitude, awe and beauty in life among patients with multiple sclerosis and psychiatric disorders

    DEFF Research Database (Denmark)

    Büssing, Arndt; Wirth, Anne Gritli; Reiser, Franz

    2014-01-01

    in life among patients with multiple sclerosis and psychiatric disorders, particularly with respect to their engagement in specific spiritual/religious practices and their life satisfaction. Methods: We conducted a cross-sectional survey with standardized questionnaires to measure engagement in various...... spiritual practices (SpREUK-P) and their relation to experiences of Gratitude, Awe and Beauty in Life and life satisfaction (BMLSS-10). In total, 461 individuals (41 +/- 13 years; 68% women) with multiple sclerosis (46%) and depressive (22%) or other psychiatric disorders (32%) participated. Results: Among......Background: Feelings of gratitude and awe facilitate perceptions and cognitions that go beyond the focus of illness and include positive aspects of one's personal and interpersonal reality, even in the face of disease. We intended to measure feelings of gratitude, awe, and experiences of beauty...

  12. BIOFEEDBACK: A NEW METHOD FOR CORRECTION OF MOTOR DISORDERS IN PATIENTS WITH MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Ya. S. Pekker

    2014-01-01

    Full Text Available Major disabling factors in multiple sclerosis is motor disorders. Rehabilitation of such violations is one of the most important medical and social problems. Currently, most of the role given to the development of methods for correction of motor disorders based on accessing natural resources of the human body. One of these methods is the adaptive control with biofeedback (BFB. The aim of our study was the correction of motor disorders in multiple sclerosis patients using biofeedback training. In the study, we have developed scenarios for training rehabilitation program computer EMG biofeedback aimed at correction of motor disorders in patients with multiple sclerosis (MS. The method was tested in the neurological clinic of SSMU. The study included 9 patients with definite diagnosis of MS with the presence of the clinical picture of combined pyramidal and cerebellar symptoms. Assessed the effectiveness of rehabilitation procedures biofeedback training using specialized scales (rating scale functional systems Kurtzke; questionnaire research quality of life – SF-36, evaluation of disease impact Profile – SIP and score on a scale fatigue – FSS. In the studied group of patients decreased score on a scale of fatigue (FSS, increased motor control (SIP2, the physical and mental components of health (SF-36. The tendency to reduce the amount of neurological deficit by reducing the points on the pyramidal Kurtske violations. Analysis of the exchange rate dynamics of biofeedback training on EMG for trained muscles indicates an increase in the recorded signal OEMG from session to session. Proved a tendency to increase strength and coordination trained muscles of patients studied.Positive results of biofeedback therapy in patients with MS can be recommended to use this method in the complex rehabilitation measures to correct motor and psycho-emotional disorders.

  13. On a Diagnosed Case of Multiple Personality Disorder -A Supplementary Report with Special Reference to Psychotherapy-

    OpenAIRE

    藤田, 裕司

    2000-01-01

    As a supplement of the study on a dignosed case of MPD (Multiple Personality Disorder), the effect of the psychotherapy was discussed. The patient was a twenty-four-year-old woman suspected of an attempted murder. In this article, continued from the previous one reporting the process of a series of ten psychotherapeutic interviews with her, the general comment on that was made, and the merits and demerits of the psychotherapy were clarified.

  14. Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications

    OpenAIRE

    Giordani Rodrigues Dos Passos; Douglas Kazutoshi Sato; Jefferson Becker; Kazuo Fujihara

    2016-01-01

    Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of e...

  15. Assessing the criminal responsibility of individuals with multiple personality disorder: legal cases, legal theory.

    Science.gov (United States)

    Behnke, S H

    1997-01-01

    This article discusses the criminal responsibility of individuals diagnosed with multiple personality disorder (MPD). First, it reviews how courts understand and assess criminal responsibility. Second, it gives an overview of how courts have applied the doctrine of criminal responsibility to individuals with MPD. Third, it explains what legal theorists say about this question. Finally, it uses a case example to illustrate how various theorists would assess the responsibility of a criminal defendant with MPD.

  16. Eosinophilia associated with disorders of immune deficiency or immune dysregulation

    Science.gov (United States)

    Williams, Kelli W.; Milner, Joshua D.; Freeman, Alexandra F.

    2015-01-01

    Synopsis Elevated serum eosinophil levels have been associated with multiple disorders of immune deficiency or immune dysregulation. Although primary immunodeficiency diseases (PIDD) are rare, it is important to consider these in the differential diagnosis of patients with eosinophilia. This review discusses the clinical features, laboratory findings, diagnosis, and genetic basis of disease of several disorders of immune deficiency or dysregulation – all which have documented eosinophilia as part of the syndrome. The article includes autosomal dominant hyper IgE syndrome, DOCK8 deficiency, PGM3 deficiency, ADA-SCID, Omenn syndrome, Wiskott-Aldrich syndrome, Loeys-Dietz syndrome, autoimmune lymphoproliferative syndrome, immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, Comel-Netherton syndrome, and severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM). PMID:26209898

  17. Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS).

    Science.gov (United States)

    Teachey, David T; Manno, Catherine S; Axsom, Kelly M; Andrews, Timothy; Choi, John K; Greenbaum, Barbara H; McMann, Joseph M; Sullivan, Kathleen E; Travis, Susan F; Grupp, Stephan A

    2005-03-15

    Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of disrupted lymphocyte homeostasis. Clinical manifestations of ALPS vary but typically include autoimmune cytopenias, organomegaly, lymphadenopathy, and increased risk of malignancies. A similar spectrum of symptoms may be seen in some patients with Evans syndrome (ES), a hematologic disorder defined by autoimmune destruction of at least 2 hematologic cell types. We hypothesized that a subset of patients diagnosed with ES may have ALPS. We screened 12 children with ES by flow cytometric analysis for CD4-/CD8- (double negative) T cells (DNTs) and with the definitive test for ALPS, defective in vitro Fas-mediated apoptosis. Six of the patients had elevated DNTs, suggestive of ALPS and also had defective Fas-mediated apoptosis. The other 6 patients displayed normal T-cell apoptosis; 5 of whom had normal DNTs, and 1 had a borderline result. Thus, 7 (58%) of 12 patients with ES had elevated DNTs suggestive of ALPS, with functional confirmation in 6 of 7. This suggests that analysis of DNTs may be a sensitive first-line screening test, serving as a marker of patients who should undergo definitive testing for ALPS. Our data further suggest that a number of patients with ES may have ALPS, a novel finding with important therapeutic implications.

  18. Assessing Eating Disorder Symptoms in Adolescence: Is There a Role for Multiple Informants?

    Science.gov (United States)

    Swanson, SA; Aloisio, KM; Horton, NJ; Sonneville, KR; Crosby, RD; Eddy, KT; Field, AE; Micali, N

    2014-01-01

    disorder presentations may be improved by using multiple sources of information. PMID:24436213

  19. An uncommon disorder with multiple skeletal anomalies: Gorlin-Goltz syndrome.

    Science.gov (United States)

    Keçeli, Onur; Coskun-Benlidayı, İlke; Benlidayı, M Emre; Erdoğan, Özgür

    2014-01-01

    Gorlin-Goltz syndrome is an uncommon disorder transmitted through autosomal dominant inheritance. This syndrome is characterized by multiple odontogenic keratocysts, along with congenital skeletal anomalies and basal cell carcinomas. A 16-year-old girl was admitted with a complaint of swelling on the lower jaw. She had multiple basal cell nevi on both hands. Multiple lytic bone lesions on radiographs were defined as odontogenic keratocysts following the biopsy. The patient was referred to the Department of Physical Medicine and Rehabilitation for detailed musculoskeletal evaluation. Adam's forward bend test revealed a hump on the right side representing right thoracic scoliosis. Cervical kyphosis, thoracic lordosis and scoliosis, bifid rib and sacral and lumbar spina bifida on plain radiographs led to the diagnosis of Gorlin-Goltz syndrome. Since early diagnosis may provide optimum surveillance for related neoplasms, it is of paramount importance for pediatricians as well as physicians dealing with the musculoskeletal system to be aware of this rare condition.

  20. The Relationship Between Multiple Sex Partners and Anxiety, Depression, and Substance Dependence Disorders: A Cohort Study

    Science.gov (United States)

    Paul, Charlotte; Bell, Melanie L.; Dickson, Nigel; Moffitt, Terrie E.; Caspi, Avshalom

    2013-01-01

    Changes in sexual behavior have resulted in longer periods of multiple serial or concurrent relationships. This study investigated the effects of multiple heterosexual partners on mental health, specifically, whether higher numbers of partners were linked to later anxiety, depression, and substance dependency. Data from the Dunedin Multidisciplinary Health and Development Study, a prospective, longitudinal study of a birth cohort born in 1972–1973 in Dunedin, New Zealand were used. The relationship between numbers of sex partners over three age periods (18–20, 21–25, and 26–32 years) and diagnoses of anxiety, depression, and substance dependence disorder at 21, 26, and 32 years were examined, using logistic regression. Interaction by gender was examined. Adjustment was made for prior mental health status. There was no significant association between number of sex partners and later anxiety and depression. Increasing numbers of sex partners were associated with increasing risk of substance dependence disorder at all three ages. The association was stronger for women and remained after adjusting for prior disorder. For women reporting 2.5 or more partners per year, compared to 0–1 partners, the adjusted odd ratios (and 95 % CIs) were 9.6 (4.4–20.9), 7.3 (2.5–21.3), and 17.5 (3.5–88.1) at 21, 26, and 32 years, respectively. Analyses using new cases of these disorders showed similar patterns. This study established a strong association between number of sex partners and later substance disorder, especially for women, which persisted beyond prior substance use and mental health problems more generally. The reasons for this association deserve investigation. PMID:23400516

  1. The relationship between multiple sex partners and anxiety, depression, and substance dependence disorders: a cohort study.

    Science.gov (United States)

    Ramrakha, Sandhya; Paul, Charlotte; Bell, Melanie L; Dickson, Nigel; Moffitt, Terrie E; Caspi, Avshalom

    2013-07-01

    Changes in sexual behavior have resulted in longer periods of multiple serial or concurrent relationships. This study investigated the effects of multiple heterosexual partners on mental health, specifically, whether higher numbers of partners were linked to later anxiety, depression, and substance dependency. Data from the Dunedin Multidisciplinary Health and Development Study, a prospective, longitudinal study of a birth cohort born in 1972-1973 in Dunedin, New Zealand were used. The relationship between numbers of sex partners over three age periods (18-20, 21-25, and 26-32 years) and diagnoses of anxiety, depression, and substance dependence disorder at 21, 26, and 32 years were examined, using logistic regression. Interaction by gender was examined. Adjustment was made for prior mental health status. There was no significant association between number of sex partners and later anxiety and depression. Increasing numbers of sex partners were associated with increasing risk of substance dependence disorder at all three ages. The association was stronger for women and remained after adjusting for prior disorder. For women reporting 2.5 or more partners per year, compared to 0-1 partners, the adjusted odd ratios (and 95 % CIs) were 9.6 (4.4-20.9), 7.3 (2.5-21.3), and 17.5 (3.5-88.1) at 21, 26, and 32 years, respectively. Analyses using new cases of these disorders showed similar patterns. This study established a strong association between number of sex partners and later substance disorder, especially for women, which persisted beyond prior substance use and mental health problems more generally. The reasons for this association deserve investigation.

  2. Has multiple personality disorder remained consistent over time? A comparison of past and recent cases.

    Science.gov (United States)

    Goff, D C; Simms, C A

    1993-10-01

    The purpose of this study was to determine whether recent descriptions of multiple personality disorder are consistent with descriptions from the past. Clinical presentations and childhood histories obtained from early case reports of multiple personality disorder published between 1800 and 1965 (N = 52) were compared with recent case reports published in the 1980s (N = 54). Recent and past cases did not differ in age at diagnosis, length of treatment, duration of follow-up, presence of child and opposite gender personalities, and exposure to hypnosis. Recent cases differed significantly from past cases in mean number of personalities (12 vs. 3), age of onset (11 vs. 20 years), proportion of males (24% vs. 44%), and in prevalence of childhood abuse histories (81% vs. 29%). The authors discuss clinical and cultural factors that may have contributed to the change over time in the number of reported cases, complexity of personality structure, and description of etiological childhood trauma. Although a core set of symptoms has consistently been associated with this disorder over time, other important aspects have not been stable.

  3. The neuropsychiatry of multiple sclerosis: focus on disorders of mood, affect and behaviour.

    Science.gov (United States)

    Paparrigopoulos, Thomas; Ferentinos, Panagiotis; Kouzoupis, Anastasios; Koutsis, George; Papadimitriou, George N

    2010-01-01

    Neuropsychiatric symptoms are common in multiple sclerosis (MS). They include two broad categories of disturbances: abnormalities in cognition, and abnormalities of mood, affect and behaviour. The present review deals with the epidemiology, clinical features, etiology and treatment of disturbances included in the second category, i.e., major depression, fatigue and sleep disorders, bipolar disorder, euphoria, pathological laughing and crying, anxiety, psychosis and personality changes. Major depression is one of the most common neuropsychiatric disorders in MS with an approximate 50% lifetime prevalence rate. Early recognition and management of depression in MS is of major importance because it is a key predictor of morbidity, mortality, quality of life, possibly physical outcome and disease exacerbations, adherence to immunomodulatory treatments and suicide risk in MS patients, as well as of the caregiver's distress and quality of life. The etiopathogenesis of neuropsychiatric disorders in MS has been incompletely investigated. It is postulated that a complex interplay of biological, disease-related, behavioural and psychosocial factors contribute to the pathophysiology of most of them. Management of neuropsychiatric symptoms in MS is often effective, although commonly based on evidence provided by case studies and uncontrolled trials. A comprehensive biopsychosocial neuropsychiatric approach is essential for the optimal care of patients with MS.

  4. Multiple scattering of polarized light in disordered media exhibiting short-range structural correlations

    Science.gov (United States)

    Vynck, Kevin; Pierrat, Romain; Carminati, Rémi

    2016-09-01

    We develop a model based on a multiple scattering theory to describe the diffusion of polarized light in disordered media exhibiting short-range structural correlations. Starting from exact expressions of the average field and the field spatial correlation function, we derive a radiative transfer equation for the polarization-resolved specific intensity that is valid for weak disorder and we solve it analytically in the diffusion limit. A decomposition of the specific intensity in terms of polarization eigenmodes reveals how structural correlations, represented via the standard anisotropic scattering parameter g , affect the diffusion of polarized light. More specifically, we find that propagation through each polarization eigenchannel is described by its own transport mean free path that depends on g in a specific and nontrivial way.

  5. Multiple scattering of polarized light in disordered media exhibiting short-range structural correlations

    CERN Document Server

    Vynck, Kevin; Carminati, Rémi

    2016-01-01

    We develop a model based on a multiple scattering theory to describe the diffusion of polarized light in disordered media exhibiting short-range structural correlations. Starting from exact expressions of the average field and the field spatial correlation function, we derive a radiative transfer equation for the polarization-resolved specific intensity that is valid for weak disorder and we solve it analytically in the diffusion limit. A decomposition of the specific intensity in terms of polarization eigenmodes reveals how structural correlations, represented via the standard anisotropic scattering parameter $g$, affect the diffusion of polarized light. More specifically, we find that propagation through each polarization eigenchannel is described by its own transport mean free path that depends on $g$ in a specific and non-trivial way.

  6. Personality characteristics and disorders in multiple sclerosis patients: assessment and treatment.

    Science.gov (United States)

    Stathopoulou, Anastasia; Christopoulos, Platon; Soubasi, Evanthia; Gourzis, Philippos

    2010-01-01

    Multiple sclerosis (MS) is a major inflammatory and demyelinating disease of the central nervous system. Although a significant incidence and prevalence of psychological disorders in MS has been reported there is limited data on the prevalence of personality disorders (PD) in these patients. Recent findings indicate the need for early diagnosis and treatment of PD in MS patients in the interests of prognosis, conformity to treatment and patient's quality of life improvement. This article summarizes existing evidence on prevalence, types and diagnostic criteria of PD in MS, clinical manifestations of personality pathology or changes in MS patients, and instruments currently used for diagnosis and assessment of PD in this group of patients. Underlying mechanisms suggested as causes of personality changes in MS patients are also discussed. The article reviews therapeutic strategies, including pharmacotherapy and psychotherapy interventions and emphasizes the need for a multidisciplinary approach to patient's treatment.

  7. Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Anxiety in Children : A Multiple Baseline Design Analysis

    Science.gov (United States)

    Jarrett, Matthew A.; Ollendick, Thomas H.

    2012-01-01

    Objective: The present study evaluated a 10-week psychosocial treatment designed specifically for children with attention-deficit/hyperactivity disorder (ADHD) and a comorbid anxiety disorder. Method: Using a nonconcurrent multiple baseline design, the authors treated 8 children ages 8-12 with ADHD, combined type, and at least 1 of 3 major anxiety…

  8. Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Anxiety in Children : A Multiple Baseline Design Analysis

    Science.gov (United States)

    Jarrett, Matthew A.; Ollendick, Thomas H.

    2012-01-01

    Objective: The present study evaluated a 10-week psychosocial treatment designed specifically for children with attention-deficit/hyperactivity disorder (ADHD) and a comorbid anxiety disorder. Method: Using a nonconcurrent multiple baseline design, the authors treated 8 children ages 8-12 with ADHD, combined type, and at least 1 of 3 major anxiety…

  9. The 7-Item Generalized Anxiety Disorder Scale as a Tool for Measuring Generalized Anxiety in Multiple Sclerosis

    OpenAIRE

    Terrill, Alexandra L.; Hartoonian, Narineh; Beier, Meghan; Salem, Rana; Alschuler, Kevin

    2015-01-01

    Background: Generalized anxiety disorder (GAD) is common in multiple sclerosis (MS) but understudied. Reliable and valid measures are needed to advance clinical care and expand research in this area. The objectives of this study were to examine the psychometric properties of the 7-item Generalized Anxiety Disorder Scale (GAD-7) in individuals with MS and to analyze correlates of GAD.

  10. Early onset post-transplant lymphoproliferative disease is associated with allograft localization

    NARCIS (Netherlands)

    Bakker, NA; van Imhoff, GW; Verschuuren, EAM; van Son, WJ; van der Heide, JJH; Veeger, NJGM; Kluin, PM; Kluin-Nelemans, HC

    2005-01-01

    Post-transplant lymphoproliferative disease (PTLD) is a major complication after solid organ transplantation. We analyzed incidence, patient characteristics, clinical presentation, and prognostic factors for treatment outcome and survival of PTLD patients transplanted at our center. Records from adu

  11. Neuromyelitis Optica Spectrum Disorder with Tumefactive Demyelination mimicking Multiple Sclerosis: a rare case

    Directory of Open Access Journals (Sweden)

    UJJAWAL eROY

    2016-05-01

    Full Text Available Neuromyelitis optica spectrum disorder (NMOSD is a diverse condition which not only encompasses isolated longitudinally extensive transverse myelitis and optic neuritis but also includes area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, and symptomatic cerebral syndrome. Imaging may reveal periependymal lesions surrounding the ventricular system or involvement of corticospinal tracts, area postrema, diencephalon and corpus callosum. Rarely there may be hemispheric tumefactive lesions which enhance in a Cloud-like fashion on gadolinium injection unlike in tumefactive multiple sclerosis where there is incomplete ring enhancement. Here, we present a case of aquaporin-4 positive relapsing NMOSD who presented to us with recurrent episodes of paraperesis with longitudinally extensive transverse myelitis and tumefactive lesions of brain on imaging which enhanced in an incomplete ring like pattern resembling multiple sclerosis.

  12. Clonality assessment of lymphoproliferative lesions using the polymerase chain reaction: An analysis of two methods

    Directory of Open Access Journals (Sweden)

    Nikhil Moorchung

    2011-01-01

    Full Text Available Background: Lymphoid malignancies are a heterogeneous group of disorders which may be difficult to differentiate from reactive proliferations even after immunohistochemistry. Polymerase chain reaction (PCR is believed to be a good adjunct tool for diagnosis. Materials and Methods: We examined 24 cases of neoplastic and non-neoplastic lymphoproliferative lesions in this study and evaluated the PCR as an additional tool in the confirmation of the diagnosis. Two different PCR methodologies were evaluated. Results: In the evaluation of the T-cell PCR, it was seen that the correlation using both the commercial kits and the custom-synthesized primers was highly significant at a P value of 0.05. Conclusions: Both the methods showed an excellent concordance for T-cell γ gene rearrangements, However, the same was not seen in the B-cell receptor rearrangements. This may be because of the small sample size or the inability of consensus V primers to recognize complementary DNA sequences in all of the V segments.

  13. Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome.

    Science.gov (United States)

    Völkl, Simon; Rensing-Ehl, Anne; Allgäuer, Andrea; Schreiner, Elisabeth; Lorenz, Myriam Ricarda; Rohr, Jan; Klemann, Christian; Fuchs, Ilka; Schuster, Volker; von Bueren, André O; Naumann-Bartsch, Nora; Gambineri, Eleonora; Siepermann, Kathrin; Kobbe, Robin; Nathrath, Michaela; Arkwright, Peter D; Miano, Maurizio; Stachel, Klaus-Daniel; Metzler, Markus; Schwarz, Klaus; Kremer, Anita N; Speckmann, Carsten; Ehl, Stephan; Mackensen, Andreas

    2016-07-14

    Autoimmune lymphoproliferative syndrome (ALPS) is a human disorder characterized by defective Fas signaling, resulting in chronic benign lymphoproliferation and accumulation of TCRαβ(+) CD4(-) CD8(-) double-negative T (DNT) cells. Although their phenotype resembles that of terminally differentiated or exhausted T cells, lack of KLRG1, high eomesodermin, and marginal T-bet expression point instead to a long-lived memory state with potent proliferative capacity. Here we show that despite their terminally differentiated phenotype, human ALPS DNT cells exhibit substantial mitotic activity in vivo. Notably, hyperproliferation of ALPS DNT cells is associated with increased basal and activation-induced phosphorylation of serine-threonine kinases Akt and mechanistic target of rapamycin (mTOR). The mTOR inhibitor rapamycin abrogated survival and proliferation of ALPS DNT cells, but not of CD4(+) or CD8(+) T cells in vitro. In vivo, mTOR inhibition reduced proliferation and abnormal differentiation by DNT cells. Importantly, increased mitotic activity and hyperactive mTOR signaling was also observed in recently defined CD4(+) or CD8(+) precursor DNT cells, and mTOR inhibition specifically reduced these cells in vivo, indicating abnormal programming of Fas-deficient T cells before the DNT stage. Thus, our results identify the mTOR pathway as a major regulator of lymphoproliferation and aberrant differentiation in ALPS.

  14. Autoimmune lymphoproliferative syndrome (ALPS) caused by Fas (CD95) mutation mimicking sarcoidosis.

    Science.gov (United States)

    Müllauer, Leonhard; Emhofer, Josef; Wohlfart, Sabine; Pichlhöfer, Bettina; Stary, Susanne; Ebetsberger, Georg; Mannhalter, Christine; Chott, Andreas

    2008-02-01

    Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder associated with defects in apoptosis, characterized by childhood onset of lymphadenopathy, splenomegaly, hyperimmunoglobulinemia, and autoimmune disease. ALPS is most frequently associated with a mutation in the cell death receptor Fas (CD95). Very rarely a mutation in caspase 10 is present. An increase of CD4/CD8 double negative T cells in the peripheral blood and lymph nodes is a feature characteristic of ALPS. Additionally, histiocytic proliferations resembling sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) were reported recently in patients with ALPS. In the rare cases with a caspase 10 mutation an accumulation of dendritic cells in lymphoid organs was noted. We describe a different, sarcoidosislike, histiocytic infiltration of lymph nodes that persisted for years in a girl, that was initially supposed to suffer from sarcoidosis, but was eventually diagnosed as ALPS, associated with a missense mutation in the intracellular death domain of Fas. This sarcoidosislike histologic picture extends the spectrum of histiocytic lymph node alterations observed in ALPS and alerts of a potential diagnostic pitfall.

  15. A Multiple Deficit Model of Reading Disability and Attention-Deficit/Hyperactivity Disorder: Searching for Shared Cognitive Deficits

    Science.gov (United States)

    McGrath, Lauren M.; Pennington, Bruce F.; Shanahan, Michelle A.; Santerre-Lemmon, Laura E.; Barnard, Holly D.; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.

    2011-01-01

    Background: This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. Methods: A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique…

  16. Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Simona Bonavita

    2013-01-01

    Full Text Available Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD, obsessive-compulsive disorder (OCD, bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS, euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions, which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

  17. Time course of changes in the development of gait disorders in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    A. M. Petrov

    2015-01-01

    Full Text Available Objective: to estimate the time course of changes in foot biomechanical function as multiple sclerosis (MS progresses in patients with different degrees of disability compared to a control group. Patients and methods. To estimate the time course of changes in gait disorders in MS, changes in foot biomechanical function were explored in 30 patients with relapsing-remitting MS. Their neurological status was evaluated using the expanded disability status scale (EDSS; pedographic examination was made applying a plantar pressure distribution system; all the patients were examined twice. During the first examination, the patients were divided into two groups: 1 minimal neurological disorders (EDSS scores of < 3.0 and 2 moderate ones (EDSS scores of ≥3.0. Results and discussion. The patients with a mild neurological deficit showed increases in foot load and its lateralization by elevating pressure on the heads of the fourth and fifth metatarsal bones, as evidenced by a significant rise in mean pressure, maximum force, and force-time integral. These changes occurred in the absence of the patients’ complaints of changes in movements. Pedographic examination revealed the changes indicating an enlarged anterior transverse arch and the lower role of the hallux in body weight transfer in the patients with a moderate neurological deficit despite the fact that there were no further visible negative changes in a motor process or progression in neurological deficit. The pedographic examination makes it possible to estimate the degree of gait disorders caused by pyramidal and/or cerebellar lesions and to identify a leading role of this or that functional system in their genesis. Pyramidal dysfunction has impact on the pressurization of the heads of the second and third metatarsal bones. Computed pedography can identify clinically subtle movement changes and estimate the time course of changes in movement disorders in MS patients, including those to evaluate

  18. Multiple sclerosis and bipolar disorders: the burden of comorbidity and its consequences on quality of life.

    Science.gov (United States)

    Carta, M G; Moro, M F; Lorefice, L; Picardi, A; Trincas, G; Fenu, G; Cocco, E; Floris, F; Bessonov, D; Akiskal, H S; Marrosu, M G

    2014-01-01

    The purpose is to measure the worsening of the Quality of Life (QoL) in people with Multiple Sclerosis (MS) and the concomitant role of co-morbid Major Depressive Disorder (MDD) and Bipolar Disorder (BD), the latter not yet studied even though it was found strictly associated with MS. 201 consecutive-MS-patients. 804 sex-and-age-matched subjects without MS, randomly selected from an epidemiological database study. Psychiatric diagnoses according to DSM-IV were determined by physicians using structured interview tools (ANTAS-SCID). Bipolar Spectrum Disorders were identified by Mood Disorders Questionnaire (MDQ). QoL was measured by SF-12. MS was the strongest determinant in worsening the QoL in the overall sample. Both MDD and BD type-II lifetime diagnoses were significantly associated with a poorer quality of life in the total sample as in cases of MS. In MS the impairment of the QoL attributable to BD type-II was even greater than that in MDD. The MS diagnosis was made differently in cases and controls. Although this may have produced false negatives in controls, it would have reinforced the null hypothesis (no role of MS in worsening the QoL); therefore, it does not invalidate the study. MDD as well BD type-II are co-determinants in worsening QoL in MS. Clinicians should consider depressive symptoms as well as the hypomanic and mixed components in MS. Additional research is required to confirm our results and further clarify the manner in which BD and the mixed symptoms of BD type-II may affect awareness of both the underlying disease and psychiatric component and finally to what extent they impact treatment adherence with the available therapies for MS. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Molecular Surveillance for Lymphoproliferative Disease Virus in Wild Turkeys (Meleagris gallopavo from the Eastern United States.

    Directory of Open Access Journals (Sweden)

    Jesse M Thomas

    Full Text Available Lymphoproliferative disease virus (LPDV is a poorly understood, oncogenic avian retrovirus of domestic turkeys that has historically been restricted to Europe and Israel. However, a recent study reported LPDV in multiple wild turkey diagnostic cases from throughout the eastern United States of America (USA. To better understand the distribution of LPDV in the eastern USA, we surveyed 1,164 reportedly asymptomatic hunter-harvested wild turkeys from 17 states for the presence of LPDV proviral DNA by PCR. In total, 564/1,164 (47% turkeys were positive for LPDV. Wild turkeys from each state had a relatively high prevalence of LPDV, although statewide prevalence varied from 26 to 83%. Phylogenetic analysis revealed two major clades of LPDV in the USA, although one was at a low frequency suggesting restricted transmission, as well as significant clustering by state of isolation. To determine the best tissue to target for diagnostic purposes, liver, spleen, and bone marrow were tested from a subset of 15 hunter-harvested wild turkeys and 20 wild turkey diagnostic cases. Overall, bone marrow provided the highest level of detection for both hunter-harvested turkeys and diagnostic cases. The sensitivity of LPDV detection between tissues was not significantly different for diagnostic cases, but was for hunter-harvested birds. These results indicate that LPDV infection is common and widespread in wild turkey populations throughout the eastern USA, even without overt signs of disease.

  20. Molecular Surveillance for Lymphoproliferative Disease Virus in Wild Turkeys (Meleagris gallopavo) from the Eastern United States.

    Science.gov (United States)

    Thomas, Jesse M; Allison, Andrew B; Holmes, Edward C; Phillips, Jamie E; Bunting, Elizabeth M; Yabsley, Michael J; Brown, Justin D

    2015-01-01

    Lymphoproliferative disease virus (LPDV) is a poorly understood, oncogenic avian retrovirus of domestic turkeys that has historically been restricted to Europe and Israel. However, a recent study reported LPDV in multiple wild turkey diagnostic cases from throughout the eastern United States of America (USA). To better understand the distribution of LPDV in the eastern USA, we surveyed 1,164 reportedly asymptomatic hunter-harvested wild turkeys from 17 states for the presence of LPDV proviral DNA by PCR. In total, 564/1,164 (47%) turkeys were positive for LPDV. Wild turkeys from each state had a relatively high prevalence of LPDV, although statewide prevalence varied from 26 to 83%. Phylogenetic analysis revealed two major clades of LPDV in the USA, although one was at a low frequency suggesting restricted transmission, as well as significant clustering by state of isolation. To determine the best tissue to target for diagnostic purposes, liver, spleen, and bone marrow were tested from a subset of 15 hunter-harvested wild turkeys and 20 wild turkey diagnostic cases. Overall, bone marrow provided the highest level of detection for both hunter-harvested turkeys and diagnostic cases. The sensitivity of LPDV detection between tissues was not significantly different for diagnostic cases, but was for hunter-harvested birds. These results indicate that LPDV infection is common and widespread in wild turkey populations throughout the eastern USA, even without overt signs of disease.

  1. Lymphoma and cerebral vasculitis in association with X-linked lymphoproliferative disease

    Institute of Scientific and Technical Information of China (English)

    Jia Zhu; Yu Zhang; Zi-Jun Zhen; Yan Chen; Juan Wang; Rui-Qing Cai; Xiao-Fei Sun

    2013-01-01

    Lymphoma is seen in up to 30% of patients with X-linked lymphoproliferative disease (XLP), but cerebral vasculitis related with XLP after cure of Burkitt lymphoma is rarely reported. We describe a case of a 5-year-old boy with XLP who developed cerebral vasculitis two years after cure of Burkitt lymphoma. He had Burkitt lymphoma at the age of 3 years and received chemotherapy (non-Hodgkin’s lymphoma-Berlin-Frankfurt-Milan-90 protocol plus rituximab), which induced complete remission over the following two years. At the age of 5 years, the patient first developed headache, vomiting, and then intel ectual and motorial retrogression. His condition was not improved after anti-infection, dehydration, or dexamethasone therapy. No tumor cells were found in his cerebrospinal fluid. Magnetic resonance imaging showed multiple non-homogeneous, hypodense masses along the bilateral cortex. Pathology after biopsy revealed hyperplasia of neurogliocytes and vessels, accompanied by lymphocyte infiltration but no tumor cell infiltration. Despite aggressive treatment, his cognition and motor functions deteriorated in response to progressive cerebral changes. The patient is presently in a vegetative state. We present this case to inform clinicians of association between lymphoma and immunodeficiency and explore an optimal treatment for lymphoma patients with compromised immune system.

  2. The 3-Year Course of Multiple Substance Use Disorders in the United States: A National Longitudinal Study.

    Science.gov (United States)

    McCabe, Sean Esteban; West, Brady T

    2017-05-01

    To examine the 3-year course of multiple co-occurring substance use disorders (SUDs) based on longitudinal survey data from a large, nationally representative sample. National estimates of the prevalence of DSM-IV SUDs were derived by analyzing data from structured, face-to-face diagnostic interviews as part of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), which collected data from a large, nationally representative sample of noninstitutionalized US adults at 2 waves (2001-2002 and 2004-2005; N = 34,653). US adults with multiple past-year SUDs at Wave 1 were substantially more likely than those with an individual past-year SUD or no SUD at Wave 1 to report at least 1 past-year SUD at Wave 2 (66.3% vs 46.0% vs 6.9%, respectively). There were several sociodemographic characteristics and psychiatric disorders (ie, male, younger age, never married, sexual minority identity, nicotine dependence, mood disorder, and personality disorder) associated with increased odds of developing multiple SUDs and having 3-year persistence of multiple SUDs. The majority of adults with multiple past-year SUDs had a lifetime personality disorder and did not utilize substance abuse treatment or other help-seeking. Multiple SUDs are associated with a more persistent 3-year course of disease over time relative to individual SUDs. Despite a more severe 3-year course and higher rates of comorbidity with other psychiatric disorders, the majority of US adults with multiple SUDs do not utilize substance abuse treatment or other help-seeking. Clinical assessments and the substance abuse literature tend to focus on drug-specific individual SUDs rather than considering the more complex multiple SUDs, which can be more challenging to treat.

  3. Molecular and cellular pathogenesis of X-linked lymphoproliferative disease.

    Science.gov (United States)

    Nichols, Kim E; Ma, Cindy S; Cannons, Jennifer L; Schwartzberg, Pamela L; Tangye, Stuart G

    2005-02-01

    X-linked lymphoproliferative disease (XLP) is an inherited immune defect caused by mutations in the Src homology 2 domain-containing gene 1A, which encodes the adapter protein, signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). SAP is expressed in T cells, natural killer (NK) cells, and NKT cells, where it binds to the cytoplasmic domain of the surface receptor SLAM (CD150) and the related receptors, 2B4 (CD244), CD84, Ly9 (CD229), NK-T-B-antigen, and CD2-like receptor-activating cytotoxic T cells. SAP also binds to the Src family tyrosine kinase Fyn and recruits it to SLAM, which leads to the generation of downstream phosphotyrosine signals. While the roles of the SLAM family receptors are only beginning to be understood, experiments suggest that these molecules regulate important aspects of lymphocyte function, such as proliferation, cytokine secretion, cytotoxicity, and antibody production. Thus, in XLP patients who lack functional SAP, the SLAM family receptors may not signal properly. This property likely contributes to the phenotypes of XLP, including fulminant infectious mononucleosis, lymphoma, and hypogammaglobulinemia. Further studies of SAP and the SLAM family receptors will provide insights into XLP and elucidate the signaling events regulating lymphocyte ontogeny and function.

  4. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders

    DEFF Research Database (Denmark)

    van de Donk, Niels W C J; Palumbo, Antonio; Johnsen, Hans Erik

    2014-01-01

    Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple...... myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype...... and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk...

  5. Annual research review: The neurobehavioral development of multiple memory systems--implications for childhood and adolescent psychiatric disorders.

    Science.gov (United States)

    Goodman, Jarid; Marsh, Rachel; Peterson, Bradley S; Packard, Mark G

    2014-06-01

    Extensive evidence indicates that mammalian memory is organized into multiple brains systems, including a 'cognitive' memory system that depends on the hippocampus and a stimulus-response 'habit' memory system that depends on the dorsolateral striatum. Dorsal striatal-dependent habit memory may in part influence the development and expression of some human psychopathologies, particularly those characterized by strong habit-like behavioral features. The present review considers this hypothesis as it pertains to psychopathologies that typically emerge during childhood and adolescence. These disorders include Tourette syndrome, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, eating disorders, and autism spectrum disorders. Human and nonhuman animal research shows that the typical development of memory systems comprises the early maturation of striatal-dependent habit memory and the relatively late maturation of hippocampal-dependent cognitive memory. We speculate that the differing rates of development of these memory systems may in part contribute to the early emergence of habit-like symptoms in childhood and adolescence. In addition, abnormalities in hippocampal and striatal brain regions have been observed consistently in youth with these disorders, suggesting that the aberrant development of memory systems may also contribute to the emergence of habit-like symptoms as core pathological features of these illnesses. Considering these disorders within the context of multiple memory systems may help elucidate the pathogenesis of habit-like symptoms in childhood and adolescence, and lead to novel treatments that lessen the habit-like behavioral features of these disorders.

  6. Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder

    DEFF Research Database (Denmark)

    Andreassen, O A; Harbo, H F; Wang, Y

    2014-01-01

    in SNPs associated with SCZ (n=21 856) and multiple sclerosis (MS) (n=43 879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16 731) and MS. We found...... significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles...... in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS...

  7. Joint source based analysis of multiple brain structures in studying major depressive disorder

    Science.gov (United States)

    Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

    2014-03-01

    We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

  8. Treatment Efficacy of Multiple Family Therapy for Chinese Families of Children with Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Ma, Joyce L C; Lai, Kelly Y C; Xia, Lily Li Li

    2017-05-30

    The treatment efficacy of multiple family therapy (MFT) for Chinese families of children with attention deficit hyperactivity disorder (ADHD) has not been studied in the past. In this paper, the effect of MFT on different aspects of the lives of the parents in the experimental group (n = 61) was compared with the effect of only the psychoeducational talks on parents in the control group (n = 53). The results of a MANOVA have shown that by the time they reached the posttreatment phase, the parents who had completed the full 42 hours of the MFT program perceived their children's ADHD symptoms as being less serious and less pathological than they had originally thought compared to the parents in the control group. The effect of MFT on parent-child relationships, parenting stress, parental efficacy, hope, and perceived social support was statistically insignificant. Contributions and limitations of our study are discussed. © 2017 Family Process Institute.

  9. A trans-diagnostic review of anxiety disorder comorbidity and the impact of multiple exclusion criteria on studying clinical outcomes in anxiety disorders.

    Science.gov (United States)

    Goldstein-Piekarski, A N; Williams, L M; Humphreys, K

    2016-06-28

    Anxiety disorders are highly comorbid with each other and with other serious mental disorders. As our field progresses, we have the opportunity to pursue treatment study designs that consider these comorbidities. In this perspective review, we first characterized the prevalence of multiple anxiety disorder comorbidity by reanalyzing national survey data, then conducted an English-language PubMed search of studies analyzing the impact of exclusion criteria on treatment outcome data. In the prevalence data, 60% of people with an anxiety disorder had one or more additional anxiety or depression diagnosis. Because our commonly applied exclusion criteria focus on a single diagnosis and do not consider a multiple comorbidity profile, the impact of the criteria may be to exclude up to 92% of anxiety disorder treatment seekers. Moreover, the findings do not suggest a consistent relationship between the number of exclusion criteria and the effect size of treatment outcomes. Thus, future studies might consider a more trans-diagnostic rationale for determining exclusion criteria, one that is generalizable to real-world settings in which multiple diagnoses commonly co-occur. The findings also encourage a more systematic reporting of rationales for the choice of-and the implications of-each exclusion criterion.

  10. Multiple dimensions of familial psychopathology affect risk of mood disorder in children of bipolar parents

    NARCIS (Netherlands)

    Wals, M; van Os, J; Reichart, CG; Hillegers, MHJ; Ormel, J; Verhulst, FC; Nolen, WA

    2004-01-01

    The aim of our study was to determine whether familial loading of unipolar disorder, bipolar disorder, and substance use disorder are associated with DSM-IV mood disorders in adolescents at risk for bipolar disorder. One hundred and forty adolescents aged 12-21 years of 86 bipolar parents participat

  11. Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications.

    Science.gov (United States)

    Dos Passos, Giordani Rodrigues; Sato, Douglas Kazutoshi; Becker, Jefferson; Fujihara, Kazuo

    2016-01-01

    Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders.

  12. Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Giordani Rodrigues Dos Passos

    2016-01-01

    Full Text Available Several animal and human studies have implicated CD4+ T helper 17 (Th17 cells and their downstream pathways in the pathogenesis of central nervous system (CNS autoimmunity in multiple sclerosis (MS and neuromyelitis optica spectrum disorders (NMOSD, challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders.

  13. Multiple sclerosis and alcohol use disorders: In-hospital mortality, extended hospital stays, and overexpenditures.

    Science.gov (United States)

    Gili-Miner, M; López-Méndez, J; Vilches-Arenas, A; Ramírez-Ramírez, G; Franco-Fernández, D; Sala-Turrens, J; Béjar-Prado, L

    2016-10-22

    The objective of this study was to analyse the impact of alcohol use disorders (AUD) in patients with multiple sclerosis (MS) in terms of in-hospital mortality, extended hospital stays, and overexpenditures. We conducted a retrospective observational study in a sample of MS patients obtained from minimal basic data sets from 87 Spanish hospitals recorded between 2008 and 2010. Mortality, length of hospital stays, and overexpenditures attributable to AUD were calculated. We used a multivariate analysis of covariance to control for such variables as age and sex, type of hospital, type of admission, other addictions, and comorbidities. The 10,249 patients admitted for MS and aged 18-74 years included 215 patients with AUD. Patients with both MS and AUD were predominantly male, with more emergency admissions, a higher prevalence of tobacco or substance use disorders, and higher scores on the Charlson comorbidity index. Patients with MS and AUD had a very high in-hospital mortality rate (94.1%) and unusually lengthy stays (2.4 days), and they generated overexpenditures (1,116.9euros per patient). According to the results of this study, AUD in patients with MS results in significant increases in-hospital mortality and the length of the hospital stay and results in overexpenditures. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Obsessive compulsive personality disorder in Progressive Supranuclear Palsy, Multiple System Atrophy and Essential Tremor.

    Science.gov (United States)

    Nicoletti, A; Luca, A; Luca, M; Donzuso, G; Mostile, G; Raciti, L; Contrafatto, D; Dibilio, V; Sciacca, G; Cicero, C E; Vasta, R; Petralia, A; Zappia, M

    2016-09-01

    aim of the study was to evaluate the presence of the Obsessive Compulsive Personality Disorder (OCPeD) in Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) and Essential Tremor (ET) and in a group of healthy subjects. patients affected by MSA, PSP and ET diagnosed according to currently accepted diagnostic criteria and a group of healthy controls were enrolled in the study. Patients with cognitive impairment were excluded from the study. The Structured Clinical Interview for Personality Disorders-II (SCID-II) has been performed to evaluate the presence of personality disorders (PeDs). The diagnosis of OCPeD was confirmed by a psychiatric interview. fifteen MSA patients (8 men and 7 women; aged 62.9 ± 7.6 years), 14 PSP patients (8 men and 6 women; aged 69.8 ± 4.4 years), 16 ET patients (10 men and 6 women; aged 70.4 ± 6.4 years) and 20 healthy subjects (10 men and 10 women; aged 65.5 ± 6.0 years) were enrolled. OCPeD was recorded in 5 (35.7%) PSP patients, 2 (13.3%) MSA patients, 2 (12.5%) ET patient and 2 (10%) controls. a low frequency of OCPeD, close to those recorded in healthy subjects, was recorded in both MSA and ET patients. Conversely an higher frequency of OCPeD, similar to PD was found among PSP patients, supporting the possibility of an impairment of common basal ganglia network possibly involving the orbito-frontal circuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Psychiatric disorders in multiple sclerosis patients Transtornos psiquiátricos em pacientes com esclerose múltipla

    OpenAIRE

    Mirella Martins Fazzito; Sérgio Semeraro Jordy; Charles Peter Tilbery

    2009-01-01

    Multiple sclerosis (MS) is a demyelinating disease showing variable clinical presentation. Optic neuritis is the most common symptom, followed by motor and sensitive manifestations. It is known that this disease may be related to several psychiatric disorders, especially depression. In this study we will discribe 5 cases of MS patients harboring psychiatric disorder related or unchained by the disease itself.Esclerose múltipla é uma doença desmielinizante com variadas apresentações clínicas. ...

  16. Does the mind fall apart in multiple personality disorder? Some proposals based on a psychoanalytic case.

    Science.gov (United States)

    Gottlieb, R M

    1997-01-01

    A psychoanalytic study of some of the phenomena of multiple personality disorder (MPD), this paper takes issue with the view that a falling apart, fragmentation, or disaggregation of the mind is at the bottom of MPD's characteristic symptoms. Since first proposed by Janet in 1889, the view that ordinarily integrated parts of the mind separate from the center, accounting for the appearance of separate "selves," has prevailed among workers in this field. The close psychoanalytic study of a case of MPD suggests that, to the contrary, the appearance of multiplicity may derive from an essentially unitary but nonetheless powerful set of organizing fantasies centering on the idea that one's body and mind can be taken over and controlled by persons other than oneself. The data of the case under study suggest, further, that certain of the details of these patients' histories of childhood sexual and physical abuse may be of great importance in explaining the extraordinary organizing power of their fantasies of being occupied and controlled. In this connection, special attention is directed to the very commonly reported experiences of forced violation and the involuntary filling and emptying of their bodies during childhood.

  17. [Treatment manual for psychotherapy of acute and posttraumatic stress disorders after multiple ICD shocks].

    Science.gov (United States)

    Jordan, J; Titscher, G; Kirsch, H

    2011-09-01

    In view of the inceasing number of implanted defibrillators in all industrial nations, the number of people who have suffered so-called multiple shocks (electrical storm, ES) also increases. Common complaints are severe and continuously recurrent massive anxiety, panic attacks, fear of death, helplessness and hopelessness, depression, nervosity and irritability as well as reclusive and uncontrollable avoidance behaviour, intrusions, nightmares, flashbacks, sleeplessness and the inability to show feelings and limitation of future perspectives. Because people with an ICD are often physically (very) ill and after multiple ICD shocks are additionally very insecure, it would seem logical if the inpatient treatment would be carried out in an institution which has close connections and is also spatially close to a cardiology department. The basis of the diagnostics is the clinical anamnesis and a systematic exploration of the trauma situation and the resulting complaints. As an additional diagnostic element psychological test procedures should be implemented to determine the core symptomatic (anxiety, depression, trauma symptoms). Psychological test procedures should be included in the diagnostics so that at the end of treatment it is obvious even to the patient which alterations have occurred. The core element of inpatient treatment is daily intensive psychotherapy and includes deep psychologically well-founded psychotherapy and behavioral therapeutic-oriented anxiety therapy as well as cognitive restructuring and elements of eye movement desensitization and reprocessing (EMDR). A follow-up examination within 4 months of the multiple shocks episode is recommended because symptoms of posttraumatic stress disorder often occur after a long latent time period.

  18. Sleep Disorders Reduce Health-Related Quality of Life in Multiple Sclerosis (Nottingham Health Profile Data in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Christian Veauthier

    2015-07-01

    Full Text Available Quality of Life (QoL is decreased in multiple sclerosis (MS, but studies about the impact of sleep disorders (SD on health-related quality of Life (HRQoL are lacking. From our original cohort, a cross-sectional polysomnographic (PSG study in consecutive MS patients, we retrospectively analysed the previously unpublished data of the Nottingham Health Profile (NHP. Those MS patients suffering from sleep disorders (n = 49 showed significantly lower HRQoL compared to MS patients without sleep disorders (n = 17. Subsequently, we classified the patients into four subgroups: insomnia (n = 17, restless-legs syndrome, periodic limb movement disorder and SD due to leg pain (n = 24, obstructive sleep apnea (n = 8 and patients without sleep disorder (n = 17. OSA and insomnia patients showed significantly higher NHP values and decreased HRQoL not only for the sleep subscale but also for the “energy” and “emotional” area of the NHP. In addition, OSA patients also showed increased NHP values in the “physical abilities” area. Interestingly, we did not find a correlation between the objective PSG parameters and the subjective sleep items of the NHP. However, this study demonstrates that sleep disorders can reduce HRQoL in MS patients and should be considered as an important confounder in all studies investigating HRQoL in MS.

  19. White matter changes in paediatric multiple sclerosis and monophasic demyelinating disorders.

    Science.gov (United States)

    Longoni, Giulia; Brown, Robert A; MomayyezSiahkal, Parya; Elliott, Colm; Narayanan, Sridar; Bar-Or, Amit; Ann Marrie, Ruth; Ann Yeh, E; Filippi, Massimo; Banwell, Brenda; Arnold, Douglas L

    2017-03-14

    Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants. Fifty-three participants with demyelinating syndromes eventually received a diagnosis of paediatric-onset multiple sclerosis. Diffusion tensor imaging measures properties of water diffusion through tissue, which normally becomes increasingly restricted and anisotropic in the brain during childhood and adolescence, as fibre bundles develop and myelinate. In the healthy paediatric participants, our data demonstrate the expected trajectory of more restricted and anisotropic white matter diffusivity with increasing age. However, in participants with multiple sclerosis, fractional anisotropy decreased and mean diffusivity of non-lesional, normal-appearing white matter progressively increased after clinical presentation, suggesting not only a failure of age-expected white matter development but also a progressive loss of tissue integrity. Surprisingly, patients with monophasic disease failed to show age-expected changes in diffusion parameters in normal-appearing white matter, although they did not show progressive loss of integrity over time. Further analysis demonstrated that participants with monophasic disease experienced different post-onset trajectories in normal-appearing white matter depending on their presenting phenotype: those with acute disseminated encephalomyelitis demonstrated abnormal trajectories of diffusion parameters compared to healthy paediatric participants, as did

  20. Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease.

    Science.gov (United States)

    Nabhani, Schafiq; Ginzel, Sebastian; Miskin, Hagit; Revel-Vilk, Shoshana; Harlev, Dan; Fleckenstein, Bernhard; Hönscheid, Andrea; Oommen, Prasad T; Kuhlen, Michaela; Thiele, Ralf; Laws, Hans-Jürgen; Borkhardt, Arndt; Stepensky, Polina; Fischer, Ute

    2015-09-01

    Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20-30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease. Copyright© Ferrata Storti

  1. Multiple Channel Exposure Therapy: Combining Cognitive-Behavioral Therapies for the Treatment of Posttraumatic Stress Disorder with Panic Attacks

    Science.gov (United States)

    Falsetti, Sherry A.; Resnick, Heidi S.; Davis, Joanne

    2005-01-01

    A large proportion of patients who present for treatment of posttraumatic stress disorder (PTSD) experience comorbid panic attacks, yet it is unclear to what extent currently available PTSD treatment programs address this problem. Here we describe a newly developed treatment, multiple-channel exposure therapy (M-CET), for comorbid PTSD and panic…

  2. An Overview of Multiple Sclerosis: Medical, Psychosocial, and Vocational Aspects of a Chronic and Unpredictable Neurological Disorder

    Science.gov (United States)

    Rumrill, Phillip D., Jr.; Roessler, Richard T.

    2015-01-01

    This article presents an overview of multiple sclerosis (MS), one of the most common neurological disorders in the western hemisphere. Medical and psychosocial aspects of the disease such as causes and risk factors, diagnosis, incidence and prevalence, symptoms, courses, and treatment are described. Existing research regarding the employment…

  3. Dubowitz syndrome is a complex comprised of multiple, genetically distinct and phenotypically overlapping disorders.

    Directory of Open Access Journals (Sweden)

    Douglas R Stewart

    Full Text Available Dubowitz syndrome is a rare disorder characterized by multiple congenital anomalies, cognitive delay, growth failure, an immune defect, and an increased risk of blood dyscrasia and malignancy. There is considerable phenotypic variability, suggesting genetic heterogeneity. We clinically characterized and performed exome sequencing and high-density array SNP genotyping on three individuals with Dubowitz syndrome, including a pair of previously-described siblings (Patients 1 and 2, brother and sister and an unpublished patient (Patient 3. Given the siblings' history of bone marrow abnormalities, we also evaluated telomere length and performed radiosensitivity assays. In the siblings, exome sequencing identified compound heterozygosity for a known rare nonsense substitution in the nuclear ligase gene LIG4 (rs104894419, NM_002312.3:c.2440C>T that predicts p.Arg814X (MAF:0.0002 and an NM_002312.3:c.613delT variant that predicts a p.Ser205Leufs*29 frameshift. The frameshift mutation has not been reported in 1000 Genomes, ESP, or ClinSeq. These LIG4 mutations were previously reported in the sibling sister; her brother had not been previously tested. Western blotting showed an absence of a ligase IV band in both siblings. In the third patient, array SNP genotyping revealed a de novo ∼ 3.89 Mb interstitial deletion at chromosome 17q24.2 (chr 17:62,068,463-65,963,102, hg18, which spanned the known Carney complex gene PRKAR1A. In all three patients, a median lymphocyte telomere length of ≤ 1st centile was observed and radiosensitivity assays showed increased sensitivity to ionizing radiation. Our work suggests that, in addition to dyskeratosis congenita, LIG4 and 17q24.2 syndromes also feature shortened telomeres; to confirm this, telomere length testing should be considered in both disorders. Taken together, our work and other reports on Dubowitz syndrome, as currently recognized, suggest that it is not a unitary entity but instead a collection of

  4. Pica in an eating disordered woman with multiple sclerosis: impulse dys-control, compulsive symptom or self-medication attempt?

    Science.gov (United States)

    Ceschin, L; Giannunzio, V; Favaro, A; Santonastaso, P

    2010-01-01

    We report about a complex case of pica in comorbidity with multiple sclerosis and binge eating disorder. Pica is classified among the feeding and eating disorders of infancy and early childhood, but there is a debate in the literature about the psychopathology and classification of this behavior. Some authors emphasize the similarities with the obsessive-compulsive spectrum disorders, whereas others propose an interpretation of pica as an addiction or as an impulsive behavior. The clinical case that we describe provides a picture of impulsive and compulsive features that are very difficult to disentangle. It is noteworthy that hypercalcemia is reported to have a protective/therapeutic effect against multiple sclerosis and seems to increase the plasmatic levels of beta-endorphins. The nature, diagnostic classification, and functions of pica are a topic worthy of future investigation.

  5. Upper airway obstruction and pulmonary abnormalities due to lymphoproliferative disease following bone marrow transplantation in children

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, B.D. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105 (United States)]|[Departments of Radiology and Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Heslop, H.E. [Department of Hematology/Oncology, St. Jude Children`s Research Hospital, Department of Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Kaste, S.C. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, Department of Radiology, University of Tennessee, Memphis, Tennessee (United States); Bodner, S. [Department of Pathology, St. Jude Children`s Research Hospital, Department of Pathology, University of Tennessee, Memphis, Tennessee (United States)

    1998-07-01

    We report three patients who developed severe supraglottic airway obstruction due to Epstein-Barr virus lymphoproliferative disease following allogeneic bone marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen in all three patients, two had supraglottic airway narrowing and two developed pulmonary lymphoproliferative disease. They were treated with unmanipulated T cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway obstruction is a radiologically detectable complication of allogeneic bone marrow transplantation in children. (orig.) With 3 figs., 1 tab., 12 refs.

  6. [Post-transplant lymphoproliferative disease in liver transplant recipients--Merkur University Hospital single center experience].

    Science.gov (United States)

    Filipec-Kanizaj, Tajana; Budimir, Jelena; Colić-Cvrlje, Vesna; Kardum-Skelin, Ika; Sustercić, Dunja; Naumovski-Mihalić, Slavica; Mrzljak, Anna; Kolonić, Slobodanka Ostojić; Sobocan, Nikola; Bradić, Tihomir; Dolić, Zrinka Misetić; Kocman, Branislav; Katicić, Miroslava; Zidovec-Lepej, Snjezana; Vince, Adriana

    2011-09-01

    Post-transplant lymphoproliferative disorder (PTLD) is an increasingly recognized condition as the number of solid organ and bone marrow transplant recipients increases. It can be a life threatening fulminant disorder and affects approximately 8% of solid organ transplant recipients. Epstein-Barr virus (EBV) is closely involved in the pathogenesis of PTLD and the majority of PTLD cases arise in response to primary infection with EBV or to re-activation of previously acquired EBV. The principal risk factors underlying the development of PTLD are the degree of overall immunosuppression and EBV serostatus of the recipient. The most commonly used pathologic classification of PTLD is the World Health Organization classification, which divides PTLD into three categories: early lesions, polymorphic PTLD, and monomorphic PTLD. Early lesions are characterized by reactive plasmacytic hyperplasia. Polymorphic PTLD may be either polyclonal or monoclonal and is characterized by destruction of the underlying lymphoid architecture, necrosis, and nuclear atypia. In monomorphic PTLD, the majority of cases (>80%) arise from B cells, similar to non-Hodgkin's lymphoma in immunocompetent hosts. The most common subtype is diffuse large B-cell lymphoma, but Burkitt's/Burkitt's-like lymphoma and plasma cell myeloma are also seen. Rarely T-cell variants occur, which include peripheral T-cell lymphomas and, rarely, other uncommon types, including gamma/delta T-cell lymphoma and T-natural killer (NK) cell varieties. Hodgkin's disease-like lymphoma is very unusual. An accurate diagnosis of PTLD requires a high index of suspicion, since the disorder may present subtly and/or extranodally. Radiologic evidence of a mass or the presence of elevated serum markers (such as increased LDH levels) are suggestive of PTLD, with positive finding on ultrasonography, computed tomography, magnetic resonance and/or positron emission tomography scanning (possibly indicating metabolically active areas) also

  7. Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder.

    Science.gov (United States)

    Campbell, Daniel B; Datta, Dibyadeep; Jones, Shaine T; Batey Lee, Evon; Sutcliffe, James S; Hammock, Elizabeth A D; Levitt, Pat

    2011-06-01

    Autism spectrum disorder (ASD) is characterized by core deficits in social behavior, communication, and behavioral flexibility. Several lines of evidence indicate that oxytocin, signaling through its receptor (OXTR), is important in a wide range of social behaviors. In attempts to determine whether genetic variations in the oxytocin signaling system contribute to ASD susceptibility, seven recent reports indicated association of common genetic polymorphisms in the OXTR gene with ASD. Each involved relatively small sample sizes (57 to 436 families) and, where it was examined, failed to identify association of OXTR polymorphisms with measures of social behavior in individuals with ASD. We report genetic association analysis of 25 markers spanning the OXTR locus in 1,238 pedigrees including 2,333 individuals with ASD. Association of three markers previously implicated in ASD susceptibility, rs2268493 (P = 0.043), rs1042778 (P = 0.037), and rs7632287 (P = 0.016), was observed. Further, these genetic markers were associated with multiple core ASD phenotypes, including social domain dysfunction, measured by standardized instruments used to diagnose and describe ASD. The data suggest association of OXTR genetic polymorphisms with ASD, although the results should be interpreted with caution because none of the significant associations would survive appropriate correction for multiple comparisons. However, the current findings of association in a large independent cohort are consistent with previous results, and the biological plausibility of participation of the oxytocin signaling system in modulating social disruptions characteristic of ASD, suggest that functional polymorphisms of OXTR may contribute to ASD risk in a subset of families.

  8. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Science.gov (United States)

    Fiala, Mark; Slade, Michael; Westervelt, Peter

    2017-01-01

    Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM); thus a diagnosis of smoldering multiple myeloma (SMM) was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM. PMID:28316846

  9. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Directory of Open Access Journals (Sweden)

    Bita Fakhri

    2017-01-01

    Full Text Available Posttransplant Lymphoproliferative Disorder (PTLD is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT. Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML. Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM; thus a diagnosis of smoldering multiple myeloma (SMM was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM.

  10. A multiple case study comparison of normal private preparatory school and substance abusing/mood disordered adolescents and their families.

    Science.gov (United States)

    Yeh, L S; Hedgespeth, J

    1995-01-01

    This multiple case study of ten families of normal private preparatory school adolescents and five families of substance abusing/mood disordered adolescents was an effort to identify factors that may suggest a relationship between the abuse of substances in adolescents who also have mood disorders and the following family factors: parental marital discord, degree of family satisfaction, and family problem-solving styles. The fifteen families completed four assessment instruments and participated in a videotaped problem-solving exercise. The results of this study showed that all members of the substance abusing/mood disordered adolescents' families rated themselves as dysfunctional in all major areas of family life. In contrast, the normal private preparatory school families reported satisfaction with most areas of family functioning. Communication styles also differed considerably between the two small groups of families. These results appear to support the importance of family evaluation and treatment when addressing the issue of adolescent substance abusers with mood disorders.

  11. Speech disorders reflect differing pathophysiology in Parkinson's disease, progressive supranuclear palsy and multiple system atrophy.

    Science.gov (United States)

    Rusz, Jan; Bonnet, Cecilia; Klempíř, Jiří; Tykalová, Tereza; Baborová, Eva; Novotný, Michal; Rulseh, Aaron; Růžička, Evžen

    2015-01-01

    Although speech disorder is frequently an early and prominent clinical feature of Parkinson's disease (PD) as well as atypical parkinsonian syndromes (APS) such as progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), there is a lack of objective and quantitative evidence to verify whether any specific speech characteristics allow differentiation between PD, PSP and MSA. Speech samples were acquired from 77 subjects including 15 PD, 12 PSP, 13 MSA and 37 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analysis of 16 speech dimensions. Dysarthria was uniformly present in all parkinsonian patients but was more severe in PSP and MSA than in PD. Whilst PD speakers manifested pure hypokinetic dysarthria, ataxic components were more affected in MSA whilst PSP subjects demonstrated severe deficits in hypokinetic and spastic elements of dysarthria. Dysarthria in PSP was dominated by increased dysfluency, decreased slow rate, inappropriate silences, deficits in vowel articulation and harsh voice quality whereas MSA by pitch fluctuations, excess intensity variations, prolonged phonemes, vocal tremor and strained-strangled voice quality. Objective speech measurements were able to discriminate between APS and PD with 95% accuracy and between PSP and MSA with 75% accuracy. Dysarthria severity in APS was related to overall disease severity (r = 0.54, p = 0.006). Dysarthria with various combinations of hypokinetic, spastic and ataxic components reflects differing pathophysiology in PD, PSP and MSA. Thus, motor speech examination may provide useful information in the evaluation of these diseases with similar manifestations.

  12. Fatigue and Sleep-Disordered Breathing in Multiple Sclerosis: A Clinically Relevant Association?

    Directory of Open Access Journals (Sweden)

    Ulf Kallweit

    2013-01-01

    Full Text Available Background. Fatigue in patients with multiple sclerosis (MS is highly prevalent and severely impacts quality of life. Recent studies suggested that sleep-disordered breathing (SDB significantly contributes to fatigue in MS. Study Objective. To evaluate the importance of routine respirography in MS patients with severe fatigue and to explore the effects of treatment with continuous positive airway pressure (CPAP. Patients and Methods. We prospectively assessed the presence of severe fatigue, as defined by a score of ≥5.0 on the Fatigue Severity Scale (FSS, in 258 consecutive MS patients. Ninety-seven patients (38% suffered from severe fatigue, whereof 69 underwent overnight respirography. Results. We diagnosed SDB in 28 patients (41%. Male sex was the only independent associate of SDB severity (P=0.003. CPAP therapy in 6 patients was associated with a significant reduction of FSS scores (5.8±0.5 versus 4.8±0.6, P=0.04, but the scores remained pathological (≥4.0 in all patients. Conclusion. Respirography in MS patients with severe fatigue should be considered in daily medical practice, because SDB frequency is high and CPAP therapy reduces fatigue severity. However, future work is needed to understand the real impact of CPAP therapy on quality of life in this patient group.

  13. Disordered and Multiple Destinations Path Planning Methods for Mobile Robot in Dynamic Environment

    Directory of Open Access Journals (Sweden)

    Yong-feng Dong

    2016-01-01

    Full Text Available In the smart home environment, aiming at the disordered and multiple destinations path planning, the sequencing rule is proposed to determine the order of destinations. Within each branching process, the initial feasible path set is generated according to the law of attractive destination. A sinusoidal adaptive genetic algorithm is adopted. It can calculate the crossover probability and mutation probability adaptively changing with environment at any time. According to the cultural-genetic algorithm, it introduces the concept of reducing turns by parallelogram and reducing length by triangle in the belief space, which can improve the quality of population. And the fallback strategy can help to jump out of the “U” trap effectively. The algorithm analyses the virtual collision in dynamic environment with obstacles. According to the different collision types, different strategies are executed to avoid obstacles. The experimental results show that cultural-genetic algorithm can overcome the problems of premature and convergence of original algorithm effectively. It can avoid getting into the local optimum. And it is more effective for mobile robot path planning. Even in complex environment with static and dynamic obstacles, it can avoid collision safely and plan an optimal path rapidly at the same time.

  14. Imagery Rescripting for Body Dysmorphic Disorder: A Multiple-Baseline Single-Case Experimental Design.

    Science.gov (United States)

    Willson, Rob; Veale, David; Freeston, Mark

    2016-03-01

    Individuals with body dysmorphic disorder (BDD) often experience negative distorted images of their appearance, and research suggests these may be linked to memories of adverse events such as bullying or teasing. This study evaluates imagery rescripting (ImR) as an intervention for BDD. In this article, we present a multiple-baseline single-case experimental design testing imagery rescripting as a brief, stand-alone intervention, with six individuals with BDD that related to aversive memories. The impact of the intervention was assessed by self-reported daily measures of symptom severity (preoccupation with appearance, appearance-related checking behaviors, appearance-related distress, and strength of belief that their main problem is their appearance) and standardized clinician ratings of BDD severity (Yale-Brown Obsessive Compulsive Scale modified for BDD). Four out of six of the participants responded positively to the intervention, with clinically meaningful improvement in symptomatology. Overall response was rapid; improvements began within the first week post-ImR intervention. From a small sample it is cautiously concluded that imagery rescripting may show promise as a module in cognitive-behavioral therapy for BDD, and is worthy of further investigation.

  15. Periventricular Lesions Help Differentiate Neuromyelitis Optica Spectrum Disorders from Multiple Sclerosis

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    Eytan Raz

    2014-01-01

    Full Text Available Objective. To compare periventricular lesions in multiple sclerosis (MS and neuromyelitis optica spectrum disorders (NMOsd. Materials and Methods. Sagittal and axial fluid attenuated inversion recovery (FLAIR sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered (“type A” or jagged-bordered (“type B” pattern. On sagittal FLAIR, the images were evaluated for presence of “Dawson’s fingers.” Results. Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson’s fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson’s fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson’s finger detection between NMOsd and MS were highly significant (P<0.001. Conclusions. Dawson’s fingers and “jagged-bordered” periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases.

  16. Optical Coherence Tomography and Magnetic Resonance Imaging in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder.

    Science.gov (United States)

    Manogaran, Praveena; Hanson, James V M; Olbert, Elisabeth D; Egger, Christine; Wicki, Carla; Gerth-Kahlert, Christina; Landau, Klara; Schippling, Sven

    2016-11-15

    Irreversible disability in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is largely attributed to neuronal and axonal degeneration, which, along with inflammation, is one of the major pathological hallmarks of these diseases. Optical coherence tomography (OCT) is a non-invasive imaging tool that has been used in MS, NMOSD, and other diseases to quantify damage to the retina, including the ganglion cells and their axons. The fact that these are the only unmyelinated axons within the central nervous system (CNS) renders the afferent visual pathway an ideal model for studying axonal and neuronal degeneration in neurodegenerative diseases. Structural magnetic resonance imaging (MRI) can be used to obtain anatomical information about the CNS and to quantify evolving pathology in MS and NMOSD, both globally and in specific regions of the visual pathway including the optic nerve, optic radiations and visual cortex. Therefore, correlations between brain or optic nerve abnormalities on MRI, and retinal pathology using OCT, may shed light on how damage to one part of the CNS can affect others. In addition, these imaging techniques can help identify important differences between MS and NMOSD such as disease-specific damage to the visual pathway, trans-synaptic degeneration, or pathological changes independent of the underlying disease process. This review focuses on the current knowledge of the role of the visual pathway using OCT and MRI in patients with MS and NMOSD. Emphasis is placed on studies that employ both MRI and OCT to investigate damage to the visual system in these diseases.

  17. Neuromyelitis optica spectrum disorder and multiple sclerosis: Differentiation by a multimodal approach.

    Science.gov (United States)

    Ota, Miho; Sato, Noriko; Okamoto, Tomoko; Noda, Takamasa; Araki, Manabu; Yamamura, Takashi; Kunugi, Hiroshi

    2015-11-01

    Neuromyelitis optica spectrum disorder (NMOSD) differs from multiple sclerosis (MS) by prognosis and approach to treatment, and it is thus important to distinguish NMOSD from MS. We evaluated the structural brain abnormalities in patients with NMOSD and with relapsing-remitting MS (RRMS) using with MRI. Twenty-one NMOSD patients with antibodies against aquaporin 4, 32 patients with RRMS, and current age- and sex- matched 39 healthy subjects underwent 3-T MRI. The differences in gray matter volume and fractional anisotropy (FA) value among the three groups were evaluated. There were significant global gray matter volume reductions of NMOSD and RRMS groups, compared to the healthy subjects. Significant and diffuse decreases in FA values were observed in both the NMOSD and RRMS patients. Significant gray matter volume and FA value reductions of the RRMS patients in the bilateral thalami and some regions were observed compared to the NMOSD patients. Larger brain structural changes were seen in the RRMS group compared to the NMOSD group, and among them, the thalamus was revealed as the important region for the discrimination of these two diseases. MRI analyses of the brain may be helpful in differentiating NMOSD from RRMS patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Ecosystemic needs assessment for children with developmental coordination disorder in elementary school: multiple case studies.

    Science.gov (United States)

    Jasmin, Emmanuelle; Tétreault, Sylvie; Joly, Jacques

    2014-11-01

    This study explored the needs of children with developmental coordination disorder (DCD) from an ecosystemic viewpoint as part of a theory-driven program evaluation process. A multiple case study needs assessment was conducted. Participants included ten children with DCD, their parents (n = 12), teachers (n = 9), and service providers (n = 6). Data collection involved semi-structured interviews, validated questionnaires, and a review of the children's records. The results support the relevance of using an ecosystemic model to assess the needs of children with DCD in their life and social contexts. More specifically, the results highlight the need to provide additional services at school, such as occupational therapy and special education, as well as information and training regarding DCD for parents and teachers. The results also point to the relevant variables to consider in an intervention program based on theory-driven evaluations. This study shows how employing an ecosystemic frame of reference provides a better understanding of the needs of children with DCD. Future research should document the ecosystemic profiles and evolution of the needs of children with DCD with a larger sample from diverse socioeconomic backgrounds using a longitudinal study design.

  19. Immunoglobulin D multiple myeloma, plasma cell leukemia and chronic myelogenous leukemia in a single patient treated simultaneously with lenalidomide, bortezomib, dexamethasone and imatinib

    Directory of Open Access Journals (Sweden)

    Naveed Ali

    2016-03-01

    Full Text Available Multiple myeloma (MM is a neoplastic lymphoproliferative disorder characterized by uncontrolled monoclonal plasma cell proliferation. Among different isotypes of MM, immunoglobulin D (IgD MM is very rare, representing only 1 to 2% of all isotypes. Chronic myelogenous leukemia (CML is a neoplastic myeloproliferative disorder of pluripotent hematopoietic stem cell, which is characterized by the uncontrolled proliferation of myeloid cells. An 88-year-old male was diagnosed simultaneously with IgD kappa MM and CML. A distinctive feature in this patient was the progression to plasma cell leukemia without any symptomatic myeloma stage. He was treated simultaneously with lenalidomide, bortezomib and imatinib. Synchronous occurrence of these rare hematological malignancies in a single patient is an exceedingly rare event. Multiple hypotheses to explain co-occurrence of CML and MM have been proposed; however, the exact etiological molecular pathophysiology remains elusive.

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

    Science.gov (United States)

    Oliveira, Joao B; 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; Rao, V Koneti

    2010-10-07

    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.

  1. Expression of HSV-1 receptors in EBV-associated lymphoproliferative disease determines susceptibility to oncolytic HSV

    NARCIS (Netherlands)

    Wang, P.Y.; Currier, M.A.; Hansford, L.; Kaplan, D.; Chiocca, E.A.; Uchida, H.; Goins, W.F.; Cohen, J.B.; Glorioso, J.C.; Kuppevelt, T.H. van; Mo, X.; Cripe, T.P.

    2013-01-01

    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. A

  2. Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

    Science.gov (United States)

    Chen, Hai; Liu, Shi-Meng; Zhang, Xu-Xiang; Liu, Ya-Ou; Li, Si-Zhao; Liu, Zheng; Dong, Hui-Qing

    2016-01-01

    Background: Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. Methods: Data including the patients’ serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables. Results: Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (χ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = −3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; χ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; χ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups. Conclusion: The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis. PMID:27569235

  3. Optical Coherence Tomography and Magnetic Resonance Imaging in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

    Science.gov (United States)

    Manogaran, Praveena; Hanson, James V. M.; Olbert, Elisabeth D.; Egger, Christine; Wicki, Carla; Gerth-Kahlert, Christina; Landau, Klara; Schippling, Sven

    2016-01-01

    Irreversible disability in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is largely attributed to neuronal and axonal degeneration, which, along with inflammation, is one of the major pathological hallmarks of these diseases. Optical coherence tomography (OCT) is a non-invasive imaging tool that has been used in MS, NMOSD, and other diseases to quantify damage to the retina, including the ganglion cells and their axons. The fact that these are the only unmyelinated axons within the central nervous system (CNS) renders the afferent visual pathway an ideal model for studying axonal and neuronal degeneration in neurodegenerative diseases. Structural magnetic resonance imaging (MRI) can be used to obtain anatomical information about the CNS and to quantify evolving pathology in MS and NMOSD, both globally and in specific regions of the visual pathway including the optic nerve, optic radiations and visual cortex. Therefore, correlations between brain or optic nerve abnormalities on MRI, and retinal pathology using OCT, may shed light on how damage to one part of the CNS can affect others. In addition, these imaging techniques can help identify important differences between MS and NMOSD such as disease-specific damage to the visual pathway, trans-synaptic degeneration, or pathological changes independent of the underlying disease process. This review focuses on the current knowledge of the role of the visual pathway using OCT and MRI in patients with MS and NMOSD. Emphasis is placed on studies that employ both MRI and OCT to investigate damage to the visual system in these diseases. PMID:27854301

  4. Optical Coherence Tomography and Magnetic Resonance Imaging in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Praveena Manogaran

    2016-11-01

    Full Text Available Irreversible disability in multiple sclerosis (MS and neuromyelitis optica spectrum disorder (NMOSD is largely attributed to neuronal and axonal degeneration, which, along with inflammation, is one of the major pathological hallmarks of these diseases. Optical coherence tomography (OCT is a non-invasive imaging tool that has been used in MS, NMOSD, and other diseases to quantify damage to the retina, including the ganglion cells and their axons. The fact that these are the only unmyelinated axons within the central nervous system (CNS renders the afferent visual pathway an ideal model for studying axonal and neuronal degeneration in neurodegenerative diseases. Structural magnetic resonance imaging (MRI can be used to obtain anatomical information about the CNS and to quantify evolving pathology in MS and NMOSD, both globally and in specific regions of the visual pathway including the optic nerve, optic radiations and visual cortex. Therefore, correlations between brain or optic nerve abnormalities on MRI, and retinal pathology using OCT, may shed light on how damage to one part of the CNS can affect others. In addition, these imaging techniques can help identify important differences between MS and NMOSD such as disease-specific damage to the visual pathway, trans-synaptic degeneration, or pathological changes independent of the underlying disease process. This review focuses on the current knowledge of the role of the visual pathway using OCT and MRI in patients with MS and NMOSD. Emphasis is placed on studies that employ both MRI and OCT to investigate damage to the visual system in these diseases.

  5. Commentary: Differentiated Measures of Temperament and Multiple Pathways to Childhood Disorders

    Science.gov (United States)

    Rothbart, Mary K.

    2004-01-01

    Provided is a commentary on articles written for a special section on temperament and childhood disorders. Temperament's contributions to the development of childhood disorders are considered both generally and specifically. Questions are raised about the use of terminology in the field, particularly the term difficult. Differentiation of outcomes…

  6. Immediate-Release Methylphenidate for ADHD in Children with Comorbid Chronic Multiple Tic Disorder

    Science.gov (United States)

    Gadow, Kenneth D.; Sverd, Jeffrey; Nolan, Edith E.; Sprafkin, Joyce; Schneider, Jayne

    2007-01-01

    Objective: To examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%). Method: Two cohorts of prepubertal children (N = 71) received placebo and three doses of…

  7. Commentary: Differentiated Measures of Temperament and Multiple Pathways to Childhood Disorders

    Science.gov (United States)

    Rothbart, Mary K.

    2004-01-01

    Provided is a commentary on articles written for a special section on temperament and childhood disorders. Temperament's contributions to the development of childhood disorders are considered both generally and specifically. Questions are raised about the use of terminology in the field, particularly the term difficult. Differentiation of outcomes…

  8. Sarcoidosis and multiple myeloma: Concurrent presentation of an unusual association

    Directory of Open Access Journals (Sweden)

    Vidya Nair

    2016-01-01

    Full Text Available Literature on concurrent association of sarcoidosis with lymphoproliferative malignancies other than lymphoma e.g. multiple myeloma is meager. The rarity of the situation prompted us to report this patient who was a 51-year-old woman with a 2-years history of breathlessness, cough with expectoration, chest pain and backache. Initial evaluation revealed mild anemia, increased alkaline phosphatase with chest skiagram showing both lower zone non homogenous opacities with calcified hilar lymph nodes. CECT chest showed mediastinal with bilateral hilar lymphadenopathy, parenchymal fibrosis, traction bronchiectasis, ground glass opacities, septal and peribronchovascular thickening affecting mid and lower lung zones bilaterally. MRI Dorsolumbar spine was suggestive of marrow infiltrative disorder. EBUS FNA of intrathoracic nodes, EBB and TBLB confirmed sarcoidosis. PET CT revealed hyper metabolic activity in lung, multiple lymph nodes and lytic bone lesions. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin IgG kappa type. Bone marrow biopsy revealed an increase in plasma cells (15%, but no granulomas. Diagnosis of Indolent or multiple myeloma with sarcoidosis was established. 12 cases of sarcoidosis and multiple myeloma have been reported in literature, and mostly preceding the onset of multiple myeloma by many years, in our case both were diagnosed concurrently.

  9. Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

    Institute of Scientific and Technical Information of China (English)

    Hai Chen; Shi-Meng Liu; Xu-Xiang Zhang; Ya-Ou Liu; Si-Zhao Li; Zheng Liu; Hui-Qing Dong

    2016-01-01

    Background:Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS).This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice.Methods:Data including the patients' serum and cerebrospinal fluid (CSF) tests,image findings,and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital,Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively.An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG)autoantibodies in CSF and serum.Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab).The Chi-square test was used to compare the categorical variables.Wilcoxon rank sum test was performed to analyze the continuous variables.Results:Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled,including 124 (71%) women and 51 (29%) men.Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (22 =6.9,P < 0.01).Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z =-3.69,P < 0.01).The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range,without significant difference between each other.Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS:0,NMOSD:67%;x2 =63.9,P < 0.01).Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS:59%,NMOSD:20%;x2 =25.7,P < 0.01).No significant difference of MOG autoantibodies was found between the two groups.Conclusion:The different CSF features combined with clinical,magnetic resonance imaging,and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

  10. Startle potentiation to uncertain threat as a psychophysiological indicator of fear-based psychopathology: An examination across multiple internalizing disorders.

    Science.gov (United States)

    Gorka, Stephanie M; Lieberman, Lynne; Shankman, Stewart A; Phan, K Luan

    2017-01-01

    Heightened reactivity to uncertain threat (U-threat) is an important individual difference factor that may characterize fear-based internalizing psychopathologies (IPs) and distinguish them from distress/misery IPs. To date, however, the majority of existing research examining reactivity to U-threat has been within individuals with panic disorder and major depressive disorder (MDD) and no prior study has directly tested this hypothesis across multiple IPs. The current study therefore explored whether heightened reactivity to U-threat is a psychophysiological indicator of fear-based psychopathology across 5 groups: current (a) social anxiety disorder (SAD); (b) specific phobia (SP); (c) generalized anxiety disorder (GAD); (d) MDD; and (c) individuals with no history of psychopathology (controls). All 160 adults completed a well-validated threat-of-shock task designed to probe responses to predictable (P-) and U-threat. Startle eyeblink potentiation was recorded as an index of aversive arousal. Results indicated that individuals with SAD and SP evidenced greater startle potentiation to U-threat, but not P-threat, relative to individuals with GAD, MDD, and controls (who did not differ). The current findings, along with the prior panic disorder and MDD literature, suggest that heightened reactivity to U-threat is a psychophysiological indicator of fear-based disorders and could represent a neurobiological organizing principle for internalizing psychopathology. The findings also suggest that individuals with fear disorders generally display a hypersensitivity to uncertain aversive events, which could contribute to their psychopathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Multiple cluster axis II comorbidity and functional outcome in severe patients with borderline personality disorder.

    Science.gov (United States)

    Palomares, Nerea; McMaster, Antonia; Díaz-Marsá, Marina; de la Vega, Irene; Montes, Ana; Carrasco, José Luis

    2016-11-01

    Current literature suggests that personality disorder comorbidity negatively contributes to both the severity and prognosis of other disorders; however, little literature has been devoted to its influence on borderline personality disorder (BPD). The objective of the present work is to study comorbidity with other personality disorders in a severe clinical sample of patients with BPD, and its relationship with global functionality. A sample of 65 patients with severe borderline personality disorder was included in the study. Clinical and functionality measures were applied in order to study comorbidity of BPD with other disorders and its relationship with functionality. Associations with other comorbid PDs were analyzed with t-tests and linear correlations. Most patients (87%) presented comorbidity with other PDs. Almost half of the sample (42%) presented more than two PDs, and cluster A (paranoid) and C (obsessive and avoidant) PD were more frequent than cluster B (histrionic and antisocial). Only the presence of avoidant PD predicted a worse functional outcome in the long term (U Mann Withney ppersonality disorder might negatively predict for prognosis.

  12. Loss-of-function mutations within the IL-2 inducible kinase ITK in patients with EBV-associated lymphoproliferative diseases.

    Science.gov (United States)

    Linka, R M; Risse, S L; Bienemann, K; Werner, M; Linka, Y; Krux, F; Synaeve, C; Deenen, R; Ginzel, S; Dvorsky, R; Gombert, M; Halenius, A; Hartig, R; Helminen, M; Fischer, A; Stepensky, P; Vettenranta, K; Köhrer, K; Ahmadian, M R; Laws, H-J; Fleckenstein, B; Jumaa, H; Latour, S; Schraven, B; Borkhardt, A

    2012-05-01

    The purpose of this study was the appraisal of the clinical and functional consequences of germline mutations within the gene for the IL-2 inducible T-cell kinase, ITK. Among patients with Epstein-Barr virus-driven lymphoproliferative disorders (EBV-LPD), negative for mutations in SH2D1A and XIAP (n=46), we identified two patients with R29H or D500T,F501L,M503X mutations, respectively. Human wild-type (wt) ITK, but none of the mutants, was able to rescue defective calcium flux in murine Itk(-/-) T cells. Pulse-chase experiments showed that ITK mutations lead to varying reductions of protein half-life from 25 to 69% as compared with wt ITK (107 min). The pleckstrin homology domain of wt ITK binds most prominently to phosphatidylinositol monophosphates (PI(3)P, PI(4)P, PI(5)P) and to lesser extend to its double or triple phosphorylated derivates (PIP2, PIP3), interactions which were dramatically reduced in the patient with the ITK(R29H) mutant. ITK mutations are distributed over the entire protein and include missense, nonsense and indel mutations, reminiscent of the situation in its sister kinase in B cells, Bruton's tyrosine kinase.

  13. The multiple dimensions of the social anxiety spectrum in mood disorders.

    Science.gov (United States)

    Fournier, Jay C; Cyranowski, Jill M; Rucci, Paola; Cassano, Giovanni B; Frank, Ellen

    2012-09-01

    Major depressive disorder and bipolar spectrum disorders are debilitating conditions associated with severe impairment. The presence of co-occurring social phobia can make the clinical course of these disorders even more challenging. To better understand the nature of social anxiety in the context of ongoing mood disorders, we report the results of exploratory factor analyses of the Social Phobia Spectrum Self-Report Instrument (SHY), a 162-item measure designed to capture the full spectrum of manifestations and features associated with social anxiety experienced across the lifespan. We examined data from 359 adult outpatients diagnosed with major depressive disorder and 403 outpatients diagnosed with a bipolar spectrum disorder. The measure was divided into its two components: the SHY-General (SHY-G), reflecting general social anxiety features, and the SHY-Specific (SHY-S), reflecting anxiety in specific situations. Exploratory factor analyses were conducted for each using tetrachoric correlation matrices and an unweighted least squares estimator. Item invariance was evaluated for important patient subgroups. Five factors were identified for the SHY-G, representing general features of social anxiety: Fear of Social Disapproval, Childhood Social Anxiety, Somatic Social Anxiety, Excessive Agreeableness, and Behavioral Submission. Seven specific-situation factors were identified from the SHY-S: Writing in Public, Dating, Public Speaking, Eating in Public, Shopping Fears, Using Public Restrooms, and Unstructured Social Interactions. The identified dimensions provide clinically valuable information about the nature of the social fears experienced by individuals diagnosed with mood disorders and could help guide the development of tailored treatment strategies for individuals with co-occurring mood disorders and social anxiety.

  14. Role of Metabolism by Intestinal Bacteria in Arbutin-Induced Suppression of Lymphoproliferative Response in vitro

    Science.gov (United States)

    Kang, Mi Jeong; Ha, Hyun Woo; Kim, Ghee Hwan; Lee, Sang Kyu; Ahn, Young Tae; Kim, Dong Hyun; Jeong, Hye Gwang; Jeong, Tae Cheon

    2012-01-01

    Role of metabolism by intestinal bacteria in arbutin-induced immunotoxicity was investigated in splenocyte cultures. Following an incubation of arbutin with 5 different intestinal bacteria for 24 hr, its aglycone hydroquinone could be produced and detected in the bacterial culture media with different amounts. Toxic effects of activated arbutin by intestinal bacteria on lymphoproliferative response were tested in splenocyte cultures from normal mice. Lipopolysaccharide and concanavalin A were used as mitogens for B- and T-cells, respectively. When bacteria cultured medium with arbutin was treated into the splenocytes for 3 days, the medium cultured with bacteria producing large amounts of hydroquinone induced suppression of lymphoproliferative responses, indicating that metabolic activation by intestinal bacteria might be required in arbutin-induced toxicity. The results indicated that the present testing system might be applied for determining the possible role of metabolism by intestinal bacteria in certain chemical-induced immunotoxicity in animal cell cultures. PMID:24116295

  15. Circadian rhythm sleep disorders in patients with multiple sclerosis and its association with fatigue: A case-control study

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Najafi

    2013-01-01

    Full Text Available Background: Circadian rhythm sleep disorders are a presentation of sleep disorders in patients with multiple sclerosis (MS. This study aims to compare this problem in MS patients with healthy people and to determine its association with chronic fatigue in MS patients. Materials and Methods: A case-control study was performed on 120 MS patients and 60 healthy subjects matched for age and sex, in 2009 in MS Clinic Alzahra Hospital. Sleep quality, rhythm and fatigue severity were assessed using PSQI (Pittsburgh sleep quality index and FSS (Fatigue severity Scale questionnaires, respectively. Its reliability and validity has been confirmed in several studies (Cronbach′s alpha = 0.83. This index has seven sections including patient′s assessment of his/her sleep, sleep duration, efficacy of routine sleep, sleep disorders, use of hypnotic medication, and dysfunction in daily activities. Results: Circadian rhythm sleep disorder was more frequent in MS patients relative to healthy subjects (P: 0.002. It was higher in MS patients with severe fatigue relative to MS patients with mild fatigue (P: 0.05. Fatigue severity was 49.9 ± 8.2 and 22.5 ± 7.4 in the first and second group, respectively. PSQI index was 7.9 ± 4.5 in patients with severe fatigue and 5.9 ± 4.5 in patients with mild fatigue and 4.5 ± 2.4 in the control group (P: 0.0001. Conclusion: Circadian rhythm sleep disorders are more frequent in MS patients and those with fatigue. Recognition and management of circadian rhythm sleep disorders in MS patients, especially those with fatigue may be helpful in improving care of these patients.

  16. Clinical characteristics of patients with lymphoproliferative neoplasms in the setting of systemic autoimmune diseases.

    Science.gov (United States)

    Suvajdzic, Nada; Djurdjevic, Predrag; Todorovic, Milena; Perunicic, Maja; Stojanović, Roksanda; Novkovic, Aleksandra; Mihaljevic, Biljana

    2012-09-01

    Clinical features of 40 lymphoproliferative neoplasm patients in the setting of systemic autoimmune diseases managed in the Clinic of Hematology during 1994-2006 were analyzed retrospectively. The classification of systemic autoimmune disease patients was as follows: 15 systemic lupus erythematosus--SLE, 11 rheumatoid arthritis--RA, 12 Sjögren's syndrome--SS, 1 scleroderma, and 1 dermatomyositis. Patients comprised 31 women and 9 men of mean age 55 years (range 33-76). Systemic autoimmune diseases preceeded the development of lymphoproliferative neoplasms in 37/40 (92.5%) patients. Mean latency period between the onset of systemic autoimmune diseases and lymphoproliferative neoplasms occurrence was significantly longer in RA (113 months) than in SLE (75 months) and SS patients (65 months)--P autoimmune diseases type or antirheumatic treatment P > 0.05. Our findings are in line with earlier reports showing a high proportion of patients with advanced disease, constitutional symptoms, extranodal manifestations, high grade histology, and low OS in the systemic autoimmune diseases setting.

  17. [Multiple system atrophy and Alzheimer's disease: a case report of a rare association of two neuro-degenerative disorders].

    Science.gov (United States)

    Rusina, R; Bourdain, F; Matej, R

    2007-12-01

    Multiple system atrophy (MSA) is a neurodegenerative disorder typically characterised by cerebellar dysfunction, parkinsonism, pyramidal signs and dysautonomy. Cognitive impairement is usually limited to a moderate subcortical dysexecutive syndrom. We report the case of a 62-year-old woman suffering from MSA who progressively developed severe dementia. Neuropathological examination confirmed the diagnosis of definite MSA and also showed histopathological hallmarks of Alzheimer's disease. This association is extremely rare in the literature. Our observation confirmes that franc dementia in MSA should prompt a search for another associated cause and underlines the usefulness of neuropathological verifications in atypical clinical pictures.

  18. 76 FR 66006 - Revised Medical Criteria for Evaluating Congenital Disorders That Affect Multiple Body Systems

    Science.gov (United States)

    2011-10-25

    ... trisomy (Edwards' syndrome or trisomy E) are usually expected to result in early death. Others such as cri... methods for establishing the existence of non-mosaic Down syndrome and other congenital disorders that... (section 110.00); Revise adult listing 10.06 and childhood listing 110.06 for non-mosaic Down syndrome;...

  19. Temperament and Attention Deficit Hyperactivity Disorder: The Development of a Multiple Pathway Model

    Science.gov (United States)

    Nigg, Joel T.; Goldsmith, H. Hill; Sachek, Jennifer

    2004-01-01

    This article outlines the parallels between major theories of attention deficit hyperactivity disorder (ADHD) and relevant temperament domains, summarizing recent research from our laboratories on (a) child temperament and (b) adult personality traits related to ADHD symptoms. These data are convergent in suggesting a role of effortful control and…

  20. Restraint and Cancellation: Multiple Inhibition Deficits in Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Schachar, Russell; Logan, Gordon D.; Robaey, Philippe; Chen, Shirley; Ickowicz, Abel; Barr, Cathy

    2007-01-01

    We used variations of the stop signal task to study two components of motor response inhibition--the ability to withhold a strong response tendency (restraint) and the ability to cancel an ongoing action (cancellation)--in children with a diagnosis of attention deficit hyperactivity disorder (ADHD) and in non-ADHD controls of similar age (ages…

  1. Facebook Role Play Addiction - A Comorbidity with Multiple Compulsive-Impulsive Spectrum Disorders.

    Science.gov (United States)

    Nathan, Deeepa; Shukla, Lekhansh; Kandasamy, Arun; Benegal, Vivek

    2016-06-01

    Background Problematic Internet use (PIU) is an emerging entity with varied contents. Behavioral addictions have high comorbidity of attention deficit hyperactivity disorder and obsessive-compulsive spectrum disorders. Social networking site (SNS) addiction and role playing game (RPG) addiction are traditionally studied as separate entities. We present a case with excessive Internet use, with a particular focus on phenomenology and psychiatric comorbidities. Case presentation Fifteen-year-old girl with childhood onset attention deficit disorder, obsessive-compulsive disorder, adolescent onset trichotillomania, and disturbed family environment presented with excessive Facebook use. Main online activity was creating profiles in names of mainstream fictional characters and assuming their identity (background, linguistic attributes, etc.). This was a group activity with significant socialization in the virtual world. Craving, salience, withdrawal, mood modification, and conflict were clearly elucidated and significant social and occupational dysfunction was evident. Discussion This case highlights various vulnerability and sociofamilial factors contributing to behavioral addiction. It also highlights the presence of untreated comorbidities in such cases. The difference from contemporary RPGs and uniqueness of role playing on SNS is discussed. SNS role playing as a separate genre of PIU and its potential to reach epidemic proportions are discussed. Conclusions Individuals with temperamental vulnerability are likely to develop behavioral addictions. Identification and management of comorbid conditions are important. The content of PIU continues to evolve and needs further study.

  2. Tubulointerstitial nephritis in a patient with probable autoimmune lymphoproliferative syndrome

    DEFF Research Database (Denmark)

    Glerup, Mia; Herlin, Troels; Rittig, Søren

    2013-01-01

    associated with glomerulonephritis and we present the first report of tubulointerstitial nephritis associated with probable ALPS. A 5-year-old girl presented with fever, vomiting, hypertension, and azotemia. No autoantibodies, viral, or streptococcal antibodies were detected. A renal biopsy showed small......-vessel vasculitis with normal glomeruli and inflammation in the interstitium. The patient responded to prednisolone treatment and obtained a full renal recovery. Symptoms of connective tissue disorder supervened and after the development of more pronounced splenomegaly, a diagnosis of ALPS was confirmed....

  3. Clinicopathological correlation of acquired hypopigmentary disorders

    Directory of Open Access Journals (Sweden)

    Anisha B Patel

    2013-01-01

    Full Text Available Acquired hypopigmentary disorders comprise a significant group of disorders that affect Indians and Asians. The pigment disturbance in darker skin individuals can be very distressing to the patient and the family. These disorders cover a wide array of pathologies including infections, autoimmune processes, lymphoproliferative disorders, and sclerosing diseases. Histological diagnosis is particularly important because treatments for these diseases are varied and specific. This review will focus on histopathological diagnosis based on clinicopathological correlation for commonly encountered disorders such as leprosy, vitiligo, lichen sclerosus, pityriasis alba (PA, and pityriasis versicolor (PV. Atypical or uncommon clinical presentation of classic diseases such as hypopigmented mycosis fungoides (HMF and hypopigmented sarcoidosis are also included.

  4. The persistence of folly: critical examination of dissociative identity disorder. Part II. The defence and decline of multiple personality or dissociative identity disorder.

    Science.gov (United States)

    Piper, August; Merskey, Harold

    2004-10-01

    In this second part of our review, we continue to explore the illogical nature of the arguments offered to support the concept of dissociative identity disorder (DID). We also examine the harm done to patients by DID proponents' diagnostic and treatment methods. It is shown that these practices reify the alters and thereby iatrogenically encourage patients to behave as if they have multiple selves. We next examine the factors that make impossible a reliable diagnosis of DID--for example, the unsatisfactory, vague, and elastic definition of "alter personality." Because the diagnosis is unreliable, we believe that US and Canadian courts cannot responsibly accept testimony in favour of DID. Finally, we conclude with a guess about the condition's status over the next 10 years.

  5. Multiple epigenetic factors predict the attention deficit/hyperactivity disorder among the Chinese Han children.

    Science.gov (United States)

    Xu, Yi; Chen, Xiang-Tao; Luo, Man; Tang, Yuqing; Zhang, Guangxiang; Wu, De; Yang, Bin; Ruan, Di-Yun; Wang, Hui-Li

    2015-05-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. Despite its prevalence, the critical factors involved in its development remain to be identified. It was recently suggested that epigenetic mechanisms probably contribute to the etiology of ADHD. The present study was designed to examine the associations of epigenetic markers with ADHD among Chinese Han children, aiming to establish the prediction model for this syndrome from the epigenetic perspective. We conducted a pair-matching case-control study, and the ADHD children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised criteria (DSM-IV-R). The expression levels of risk genes DAT1, DRD4, DRD5, as well as their promoter methylation, were determined respectively, followed by the expression profiles of histone-modifying genes p300, MYST4, HDAC1, MeCP2. The multivariate logistic regressions were performed to establish ADHD prediction models. All of the seven genes tested were identified as risk factors for ADHD. The methylation of one critical CpG site located upstream of DRD4 was shown to affect its transcription, suggesting a role in ADHD's development. Aberrant DNA methylation and histone acetylation were indicated in ADHD patients. In addition, a prediction model was established using the combination of p300, MYST4 and HDAC1, with the accuracy of 0.9338. This is, to our knowledge, the first study to clearly demonstrate the associations between epigenetic markers and ADHD, shedding light on the preliminary diagnosis and etiological studies of this widespread disorder.

  6. Predicting quality of life in multiple sclerosis: accounting for physical disability, fatigue, cognition, mood disorder, personality, and behavior change.

    Science.gov (United States)

    Benedict, Ralph H B; Wahlig, Elizabeth; Bakshi, Rohit; Fishman, Inna; Munschauer, Frederick; Zivadinov, Robert; Weinstock-Guttman, Bianca

    2005-04-15

    Health-related quality of life (HQOL) is poor in multiple sclerosis (MS) but the clinical precipitants of the problem are not well understood. Previous correlative studies demonstrated relationships between various clinical parameters and diminished HQOL in MS. Unfortunately, these studies failed to account for multiple predictors in the same analysis. We endeavored to determine what clinical parameters account for most variance in predicting HQOL, and employability, while accounting for disease course, physical disability, fatigue, cognition, mood disorder, personality, and behavior disorder. In 120 MS patients, we measured HQOL (MS Quality of Life-54) and vocational status (employed vs. disabled) and then conducted detailed clinical testing. Data were analyzed by linear and logistic regression methods. MS patients reported lower HQOL (pPhysical HQOL was predicted by fatigue, depression, and physical disability. Mental HQOL was associated with only depression and fatigue. In contrast, vocational status was predicted by three cognitive tests, conscientiousness, and disease duration (p<0.05). Thus, for the first time, we predicted HQOL in MS while accounting for measures from these many clinical domains. We conclude that self-report HQOL indices are most strongly predicted by measures of depression, whereas vocational status is predicted primarily by objective measures of cognitive function. The findings highlight core clinical problems that merit early identification and further research regarding the development of effective treatment.

  7. Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

    Science.gov (United States)

    2015-07-03

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neurotoxicity; Pain; Unspecified Adult Solid Tumor, Protocol Specific

  8. Methemoglobinemia in Young Patients With Hematologic Cancer or Aplastic Anemia Treated With Dapsone

    Science.gov (United States)

    2010-11-04

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Methemoglobinemia; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm

  9. Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)

    Science.gov (United States)

    2016-03-29

    Myelodysplastic and Myeloproliferative Disorders; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Multiple Myeloma; Plasma Cell Dyscrasia; Lymphoproliferative Disorders; Hematologic Diseases

  10. Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer

    Science.gov (United States)

    2017-09-20

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm

  11. Multiple self-healing squamous epithelioma in different ethnic groups: more than a founder mutation disorder?

    DEFF Research Database (Denmark)

    D'Alessandro, Mariella; Coats, Stephanie E; Morley, Susan M

    2007-01-01

    Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith Disease, is a rare cancer-associated genodermatosis with an autosomal dominant inheritance. Affected patients suffer from recurrent skin lesions, which clinically and histologically resemble keratoacanthomas or well-d...

  12. Report from the european myeloma network on interphase FISHin multiple myeloma and related disorders

    DEFF Research Database (Denmark)

    Ross, Fiona; Avet-Loiseau, Herve; Ameye, Genevieve;

    2012-01-01

    The European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21 laboratori...

  13. Trisomy 12 in a Case of Multiple Cutaneous Squamous Cell Carcinoma in Association with Chronic Lymphocytic Leukemia

    Institute of Scientific and Technical Information of China (English)

    XU Zhou-min; CHEN Yan; GAO Wei-ran

    2007-01-01

    Chronic lymphocytic leukaemia (CLL), which shares clinical and morphological overlap with small lymphocytic lyjmphoma (SLL), is a low-grade clonal B-cell lymphoproliferative disorder that accounts for 25% of all cases of leukaemia in Western countries, while it is considered rare in Oriental patients and is thought to constitute only 2% of all leukemias in these patients[1]. CLL is associated with an increased incidence of secondary malignant neoplasms, such as brain tumors, melanomas, and gastrointestinal-tract carcinomas[2]. However, the simulataneous occurrence of CLL and cutaneous squamous cell carcinoma (SCC) is rarely reported. We present here a case of CLL with multiple SCC on the face. Subsequent studies demonstrated the patient to have a trisomy 12 identified in bone marrow specimen.

  14. Multiple Ocular and Systemic Disorders in Association with Bilateral Duane's Retraction Syndrome

    Science.gov (United States)

    Zare, Mohammad Ali; Akbari, Mohammad Reza; Kiarudi, Mohammad Yaser; Mehrjardi, Hadi Zare

    2016-01-01

    Duane's retraction syndrome (DRS) is characterized by limitations in horizontal eye movements, globe retraction, and palpebral fissure narrowing on attempted adduction. This disorder is caused by a disturbance in innervation originating in the brain stem and represents <1% of all cases of strabismus. It is postulated that this syndrome is due to an insult during the early weeks (8–10 weeks) of pregnancy and is 10–20 times more frequently associated with other systemic congenital anomalies. This case report of bilateral DRS included bilateral iris-retinal coloboma and congenital heart disease, sensory hearing loss, and inguinal hernia. PMID:27555711

  15. The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Fu J

    2016-04-01

    Full Text Available Jie Fu,1 Lilei Peng,2 Xiaogang Li1 1Department of Neurology, 2Department of Neurosurgery, The Affiliated Hospital of Luzhou Medical College, Luzhou, People’s Republic of China Objective: Vortioxetine is a novel antidepressant approved for the treatment of major depressive disorder by the US Food and Drug Administration in September 2013. This meta-analysis assessed the efficacy and safety of different doses of vortioxetine for generalized anxiety disorder of adults.Methods: PubMed, Cochrane Library, PsycINFO, and Clinical Trials databases were searched from 2000 through 2015. The abstracts of the annual meetings of the American Psychiatric Association and previous reviews were searched to identify additional studies. The search was limited to individual randomized controlled trials (RCTs, and there was no language restriction. Four RCTs met the selection criteria. These studies included 1,843 adult patients. Results were expressed as odds ratios (ORs and 95% confidence intervals (CIs. The data were pooled with a random-effects or fixed-effects model.Results: The results showed that multiple doses (2.5, 5, and 10 mg/d of vortioxetine did not significantly improve the generalized anxiety disorder symptoms compared to placebo (OR=1.16, 95% CI=0.84–1.60, Z=0.89, P=0.38; OR=1.41, 95% CI=0.82–2.41, Z=1.25, P=0.21; OR=1.05, 95% CI=0.76–1.46, Z=0.32, P=0.75, respectively. We measured the efficacy of 2.5 mg/d vortioxetine compared to 10 mg/d, and no significant differences were observed. The common adverse effects included nausea and headache. With increased dose, nausea was found to be more frequent in the vortioxetine (5 and 10 mg/d group (OR=2.99, 95% CI=1.31–6.84, Z=2.60, P=0.009; OR=2.80, 95% CI=1.85–4.25, Z=4.85, P<0.00001, respectively, but no significant differences were observed for headache.Conclusion: The results showed no significant improvement in the treatment of generalized anxiety disorder for vortioxetine compared to placebo

  16. Capturing domain knowledge from multiple sources: the rare bone disorders use case

    OpenAIRE

    Groza, Tudor; Tudorache, Tania; Peter N Robinson; Zankl, Andreas

    2015-01-01

    Background Lately, ontologies have become a fundamental building block in the process of formalising and storing complex biomedical information. The community-driven ontology curation process, however, ignores the possibility of multiple communities building, in parallel, conceptualisations of the same domain, and thus providing slightly different perspectives on the same knowledge. The individual nature of this effort leads to the need of a mechanism to enable us to create an overarching and...

  17. Effects of Psychiatric Disorders on Labor Market Outcomes: A Latent Variable Approach Using Multiple Clinical Indicators.

    Science.gov (United States)

    Banerjee, Souvik; Chatterji, Pinka; Lahiri, Kajal

    2017-02-01

    In this paper, we estimate the effect of psychiatric disorders on labor market outcomes using a structural equation model with a latent index for mental illness, an approach that acknowledges the continuous nature of psychiatric disability. We also address the potential endogeneity of mental illness using an approach proposed by Lewbel (2012) that relies on heteroscedastic covariance restrictions rather than questionable exclusion restrictions for identification. Data come from the US National Comorbidity Survey - Replication and the National Latino and Asian American Study. We find that mental illness adversely affects employment and labor force participation and also reduces the number of weeks worked and increases work absenteeism. To assist in the interpretation of findings, we simulate the labor market outcomes of individuals meeting diagnostic criteria for mental disorder if they had the same mental health symptom profile as individuals not meeting diagnostic criteria. We estimate potential gains in employment for 3.5 million individuals, and reduction in workplace costs of absenteeism of $21.6 billion due to the resultant improvement in mental health. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Epstein-Barr virus (EBV)-positive sporadic burkitt lymphoma: an age-related lymphoproliferative disorder?

    Science.gov (United States)

    Satou, Akira; Asano, Naoko; Nakazawa, Atsuko; Osumi, Tomoo; Tsurusawa, Masahito; Ishiguro, Atsushi; Elsayed, Ahmed Ali; Nakamura, Naoya; Ohshima, Koichi; Kinoshita, Tomohiro; Nakamura, Shigeo

    2015-02-01

    Epstein-Barr virus (EBV) is detected in 20% to 30% of sporadic Burkitt lymphoma (sBL). However, only a few studies of EBV-positive (EBV) sBL have been reported, and its characteristics still remain controversial. To highlight the features of EBV sBL, we compared the clinicopathologic characteristics of 33 cases of EBV and 117 cases of EBV-negative (EBV) sBL in Japan. EBV sBL showed significantly higher age distribution (median, 42 vs. 13 y; PEBV group showed significantly higher incidence of involvement of tonsil (P=0.027), adrenal gland (P=0.011), and cervical lymph node (P=0.040). In addition, the EBV group tended to have higher incidence of nodal involvement (P=0.078) and involvement of para-aorta lymph node (P=0.084) and heart (P=0.050). In contrast, the gastrointestinal tract was less frequently affected in EBV sBL (P=0.024). In addition, the less positivity for MUM1 (P=0.020) of EBV sBL was highlighted. These results indicate that biological behavior and pathogenesis of EBV sBL might be different from those of EBV sBL. Our results demonstrate that EBV sBL has an aspect of age-related disease and is a distinct clinicopathologic subtype, which should be distinguished from EBV sBL.

  19. Understanding Drug Resistance to Targeted Therapeutics in Malignant B-Cell Lymphoproliferative Disorders (B-LPDs)

    Science.gov (United States)

    2014-10-01

    CD267/TACI-(PE) & CD268/BCMA-(PE) from BioLegend (San Diego , CA), and CD256/APRIL-(APC) from R&D Systems (Minneapolis, MN). Results: Analysis...mitochondrial profiling in CLL to coincide with selected expression profile. New flow based quantitative methods by Affimetrix (ebioscience,San Diego , VA...Gabrail N, Stock W, Strair R, Rivera VM, Albitar M, Bedrosian CL, Giles FJ. A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel

  20. Intracellular inclusion bodies in 14 patients with B cell lymphoproliferative disorders.

    OpenAIRE

    Peters, O.; Thielemans, C; Steenssens, L; M. de Waele; HIJMANS, W; Van Camp, B

    1984-01-01

    Two types of intracytoplasmic inclusion were detected by immunofluorescence microscopy in 12 patients with chronic lymphocytic leukaemia and two patients with a leukaemic phase of well differentiated lymphocytic lymphoma. Further analysis with light- and electron microscopy, showed that most inclusion bodies were rod-like crystalline structures. However, in three patients they consisted of amorphous vesicular precipitates. Immunological studies revealed the presence of immunoglobulins of the ...

  1. A diagnostic mystery solved by electron microscopy: a case of an "atypical" lymphoproliferative disorder.

    Science.gov (United States)

    Lee, Sophie; Graham, Linda M; Chan, George; Ruskova, Anna

    2012-10-01

    An elderly woman with a previous diagnosis of atypical chronic lymphocytic leukemia (CLL) was noted to have a strikingly abnormal blood film, with the lymphocytes displaying numerous large cytoplasmic granules. This appearance had not been described before in the literature to the best of the authors' knowledge. After a series of investigations, electron microscopy was eventually performed, which demonstrated that the abnormal granules were composed of immunoglobulin crystals. The immunofixation study confirmed that they were monoclonal IgM paraprotein. These results led to a change of diagnosis to lymphoplasmacytic lymphoma. This report illustrates how electron microscopy can be used as a valuable additional diagnostic tool in difficult cases.

  2. Lymphoproliferative disorder in pleural effusion in a subject with past asbestos exposure

    Directory of Open Access Journals (Sweden)

    Naofumi Hara

    2015-01-01

    Full Text Available Primary effusion lymphoma (PEL is a subtype of non-Hodgkin lymphoma that presents as serous effusions without detectable masses or organomegaly. Here we report a case of PEL-like lymphoma in a patient with past asbestos exposure. A 65-year-old man was referred to our hospital due to dyspnea upon exertion. He had been exposed to asbestos for three years in the construction industry. Chest X-ray and CT images demonstrated left pleural effusion. Cytological analysis of the pleural effusion revealed large atypical lymphocytes with distinct nuclear bodies and high nucleus-to-cytoplasm ratio. Immunohistochemical analyses showed that the cells were CD20+, CD3−, CD5−, and CD10−. These findings led to a diagnosis of diffuse large B-cell lymphoma. PEL or PEL-like lymphoma should be considered a potential cause of pleural effusion in subjects with past asbestos exposure.

  3. Native kidney post-transplant lymphoproliferative disorder in a non-renal transplant patient.

    Science.gov (United States)

    Araya, Carlos E; Mehta, Mansi B; González-Peralta, Regino P; Hunger, Stephen P; Dharnidharka, Vikas R

    2009-06-01

    PTLD is an important post-transplant complication. Although PTLD affects kidney allografts after renal transplantation, it has not been reported in native kidneys of other solid organ recipients. Herein, we report a child who underwent an orthotropic liver transplant for cryptogenic cholestatic hepatitis and developed fever, generalized lymphadenopathy, chronic EBV viremia, and lymphatic PTLD. Subsequently, she also developed gross hematuria and nephrotic range proteinuria. Kidney histology revealed EBV-positive mononuclear infiltrates within the renal parenchyma consistent with PTLD. Electron microscopy examination demonstrated subepithelial electron-dense deposits consistent with a membranous glomerulopathy pattern. The PTLD was successfully treated with reduced immunosuppression and cyclic cyclophosphamide, rituximab, and prednisone, but the renal disease progressed to end-stage renal failure within two yr. Repeat kidney histology showed chronic nephropathy and membranous glomerulopathy without PTLD infiltrates or detectable EBV staining, although chronic viremia persisted. To our knowledge, this is the first such child to be reported and highlights the importance of remaining vigilant for renal PTLD even in non-kidney organ recipients.

  4. Emerging therapeutic strategies for Epstein-Barr virus+ post-transplant lymphoproliferative disorder.

    Science.gov (United States)

    Hatton, Olivia; Martinez, Olivia M; Esquivel, Carlos O

    2012-05-01

    De novo malignancies represent an increasing concern in the transplant population, particularly as long-term graft and patient survival improves. EBV-associated B-cell lymphoma in the setting of PTLD is the leading malignancy in children following solid organ transplantation. Therapeutic strategies can be categorized as pharmacologic, biologic, and cell-based but the variable efficacy of these approaches and the complexity of PTLD suggest that new treatment options are warranted. Here, we review current therapeutic strategies for treatment of PTLD. We also describe the life cycle of EBV, addressing the viral mechanisms that contribute to the genesis and persistence of EBV+ B-cell lymphomas. Specifically, we focus on the oncogenic signaling pathways activated by the EBV LMP1 and LMP2a to understand the underlying mechanisms and mediators of lymphomagenesis with the goal of identifying novel, rational therapeutic targets for the treatment of EBV-associated malignancies.

  5. Diagnostic value of clonality of surface immunoglobulin light and heavy chains in malignant lymphoproliferative disorders.

    Science.gov (United States)

    Batata, A; Shen, B

    1993-08-01

    Cell suspensions from the peripheral blood of B-chronic lymphoid leukemias (B-CLL, n = 274) and reactive lymphocytosis (RLC, n = 132) and from solid tissue samples of B-non-Hodgkin's lymphoma (B-NHL, n = 466) and reactive lymphadenopathy (RLA, n = 324) were analyzed to evaluate the diagnostic value of clonality of L- and H- chains in B-CLL and B-NHL. Cutoff levels for monoclonal L-chain (mono-L) and monoclonal H-chain (mono-H) were defined. In B-CLL, the association patterns of L- and H- chains were as follows: mono-L/mono-H, 245 cases (89.42%); mono-L/polyclonal H chain (poly-H), 4 (1.46%); polyclonal L chain (poly-L)/mono-H, 2 (0.73%); poly-L/poly-H, 2 (0.73%); undetected (und)-L/mono-H, 6 (2.19%); and und-L/und-H, 15 (5.47%). In B-NHL, the association patterns were mono-L/mono-H, 433 cases (92.92%); mono-L/poly-H, 4 (0.86%); poly-L/mono-H, 8 (1.72%); poly-L/poly-H, 2 (0.43%); und-L/mono-H, 4 (0.86%); and und-L/und-H, 15 (3.22%). Monoclonality of H chains are complementary to L-chain restriction, especially in the cases with poly-L or und-L, and should be considered as a positive criterion in determining surface immunoglobulin (SIg) clonality. Monoclonality of SIg assessed by both L and H chains is both sensitive and specific for the diagnosis of B-CLL and B-NHL, and their differentiation from RLC and RLA, since none of the cases of RLC and RLA showed monoclonal SIg.

  6. Bone marrow involvement by lymphoproliferative disorders after renal transplantation: PTLD. Int. Survey

    Directory of Open Access Journals (Sweden)

    Morteza Izadi

    2012-01-01

    Conclusions: Renal recipients with BM PTLD represent worse outcome and more unfavorable histopathological phenomenon than in other organ involvements. Moreover, a concomitant PTLD involvement site in liver was found which necessitates full hepatic evaluation for a potential complication by the disease in renal recipients whose BM is involved.

  7. Multiple episodes in children and adolescents with bipolar disorder: comorbidity, hospitalization, and treatment (data from a cohort of 8,129 patients of a national managed care database).

    Science.gov (United States)

    Castilla-Puentes, Ruby

    2008-01-01

    The purpose of this study was to delineate the prevalence, demographic characteristics, comorbidity, hospitalization, and medication use of a large cohort of patients with and without multiple episodes per year. We hypothesized that children and adolescents with multiple episodes per year would have a higher comorbidity and require more hospitalizations and pharmacological treatment than their counterparts without multiple episodes. Analysis was conducted on a cohort of 8,129 children and adolescents patients (bipolar disorders (BD), from the Integrated Healthcare Information Services (IHCIS) identified from June 30, 2000 to July 1, 2003. Demographics variables, type of hospitalization, and psychotropic medication used in the year of follow-up were compared between children and adolescents with multiple and those without multiple episodes per year. Included were 58 patients with multiple episodes (defined as: > or = 4 or more reports of inpatient treatment for any affective disorders per year) and 8,071 without multiple episodes. Children and adolescents with multiple episodes versus those without multiple episodes were differentiated as follows: more comorbid attention deficit disorder (ADD) (80.9% versus 29.4%) (chi2 = 70.61, df = 1, p children and adolescents with multiple episodes per year present a higher comorbidity and require more hospitalizations and pharmacological treatment than those without multiple episodes. The diagnosis and treatment of children and adolescents with BD will have to take into account the high comorbidity of ADD mainly in children and adolescents with multiple episodes. Future prospective studies will help to better characterize the impact of multiple episodes in the course of pediatric BD and facilitate appropriate treatment strategies.

  8. Multiple benefits of personal FM system use by children with auditory processing disorder (APD).

    Science.gov (United States)

    Johnston, Kristin N; John, Andrew B; Kreisman, Nicole V; Hall, James W; Crandell, Carl C

    2009-01-01

    Children with auditory processing disorders (APD) were fitted with Phonak EduLink FM devices for home and classroom use. Baseline measures of the children with APD, prior to FM use, documented significantly lower speech-perception scores, evidence of decreased academic performance, and psychosocial problems in comparison to an age- and gender-matched control group. Repeated measures during the school year demonstrated speech-perception improvement in noisy classroom environments as well as significant academic and psychosocial benefits. Compared with the control group, the children with APD showed greater speech-perception advantage with FM technology. Notably, after prolonged FM use, even unaided (no FM device) speech-perception performance was improved in the children with APD, suggesting the possibility of fundamentally enhanced auditory system function.

  9. Disorder, fluctuations and electron interactions in doped semiconductors: A multiple-scattering approach

    Science.gov (United States)

    Ghazali, A.; Serre, J.

    1985-02-01

    Using a multiple-scattering method, we estimate the relative importance of both scattering and concentration-fluctuation effects on the band tailing and on interband optical absorption spectra. In addition, we show that as the impurity concentration decreases, the band tail gradually splits off from the main band, forming an impurity band. Spectral-density analysis allows one to distinguish between quasi-atomic and extended states. It is found that even when no gap appears, a significant part of electrons in the tail has a quasi-atomic character. Compensation effects have also been analyzed. Finally, our results are discussed and compared with various experiments.

  10. Fluorodeoxyglucose positron emission tomography (FDG-PET) for monitoring lymphadenopathy in the autoimmune lymphoproliferative syndrome (ALPS).

    Science.gov (United States)

    Rao, V Koneti; Carrasquillo, Jorge A; Dale, Janet K; Bacharach, Stephen L; Whatley, Millie; Dugan, Faith; Tretler, Jean; Fleisher, Thomas; Puck, Jennifer M; Wilson, Wyndham; Jaffe, Elaine S; Avila, Nilo; Chen, Clara C; Straus, Stephen E

    2006-02-01

    Autoimmune lymphoproliferative syndrome (ALPS) is associated with mutations that impair the activity of lymphocyte apoptosis proteins, leading to chronic lymphadenopathy, hepatosplenomegaly, autoimmunity, and an increased risk of lymphoma. We investigated the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in discriminating benign from malignant lymphadenopathy in ALPS. We report that FDG avidity of benign lymph nodes in ALPS can be high and, hence, by itself does not imply presence of lymphoma; but FDG-PET can help guide the decision for selecting which of many enlarged nodes in ALPS patients to biopsy when lymphoma is suspected.

  11. Evidence of abnormality of lymphocyte uroporphyrinogen synthase in family members of patients with lymphoproliferative diseases.

    Science.gov (United States)

    Lahav, M; Epstein, O; Schoenfeld, N; Nemesh, L; Shaklai, M; Atsmon, A

    1985-01-01

    Patients with active lymphoproliferative diseases (LPD) were shown to have high activity of lymphocyte uroporphyrinogen synthase (L-UROS), the enzyme which converts porphobilinogen to uroporphyrinogen. The mean L-UROS activity of 64 first-degree relatives of patients with LPD was significantly higher than that of a control group and 45% of these relatives had pathological values of L-UROS. L-UROS activity was also determined in the spouses of 2 patients and was pathologically elevated in both. The pattern of pathological values among family members may indicate the presence of a communicable agent.

  12. Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

    Science.gov (United States)

    Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

    2016-03-01

    Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility

  13. [Conduction disorders at multiple levels during the acute phase of a myocardial infarct: an electrophysiological study].

    Science.gov (United States)

    García Burgos, A; Rangel Abundis, A; Castaño, R; Ramos, M A; Badui, E

    1993-01-01

    Forty patients with a diagnosis of acute myocardial infarction (anterior 24, and inferior 16) were studied. Of these patients, 37.5% manifested second and third degree atrioventricular (AV) block as a complication; another 30% showed complete right bundle branch and left anterior hemiblock. Right bundle branch and left posterior hemiblock were evidenced in 12.5% of the subjects. There was 20% with complete left bundle branch block. Electrophysiologic studies were performed in all patients to assess the site of block. A direct relation was found between the surface ECG and the His bundle electrogram studies in patients with an inferior myocardial infarction and AV block, both procedures located the conduction disturbances at the AV node (suprahisian block), in contrast to patients with anteroseptal myocardial infarction whose surface ECG only showed bundle branch block or fascicular block. The His bundle electrogram registered multiple levels of AV block, 70% with troncular and infrahisian block that gave way to sudden AV block. The mechanism responsible for this block was considered to be a functional longitudinal dissociation of conduction system due to an acute ischemic injury of the His bundle, more than a sudden and simultaneous failure of all the bundle branch of His. We conclude that electrophysiologic studies are a useful procedure for identification of a group of patients with multiple AV conduction disturbances that have a less favorable prognosis than those with only suprahisian level of block.

  14. Similar or disparate brain patterns? The intra-personal EEG variability of three women with multiple personality disorder.

    Science.gov (United States)

    Lapointe, A R; Crayton, J W; DeVito, R; Fichtner, C G; Konopka, L M

    2006-07-01

    Quantitative EEG was used to assess the intra-personal variability of brain electrical activity for 3 women diagnosed with Multiple Personality Disorder (MPD). Two separate control groups (within-subject and between-subject) were used to test the hypothesis that the intra-personal EEG variability between 2 alters would be less than the interpersonal EEG variability between 2 controls, and similar to the intra-personal EEG variability of a single personality. This hypothesis was partially supported. In general, the 2 EEG records of a MPD subject (alter 1 vs. alter 2) were more different from one another than the 2 EEG records of a single control, but less different from one another than the EEG records of 2 separate controls. Most of the EEG variability between alters involved beta activity in the frontal and temporal lobes.

  15. A comparison of three Rorschach diagnostic systems and use of the Hand Test for detecting multiple personality disorder in outpatients.

    Science.gov (United States)

    Young, G R; Wagner, E E; Finn, R F

    1994-06-01

    Eleven individuals diagnosed with multiple personality disorder (MPD) on the basis of clinical observation by experienced therapists plus elevated scores on the Dissociative Experiences Scale (DES; Bernstein & Putnam, 1986) were administered the Rorschach Inkblot Test and the Hand Test. Results from the sample (n = 11) and a matched control group (N = 22) were analyzed and discussed in accordance with previous Rorschach diagnostic systems. The Wagner Signs diagnosed 91% (n = 10) of the MPD cases in this outpatient sample, with no false positives. The Labott Signs were found to have no utility, and the Barach Signs, when they occurred, seemed to be diagnostic of MPD but yielded a high rate of false negatives. Hand Test results were analyzed and found to be possibly diagnostic of MPD. Tentative criteria were proposed for its use as an additional tool for diagnosing MPD.

  16. Disorder-induced incoherent scattering losses in photonic crystal waveguides: Bloch mode reshaping, multiple scattering, and breakdown of the Beer-Lambert law

    Science.gov (United States)

    Patterson, M.; Hughes, S.; Schulz, S.; Beggs, D. M.; White, T. P.; O'Faolain, L.; Krauss, T. F.

    2009-11-01

    Through a combined theoretical and experimental study of disorder-induced incoherent scattering losses in slow-light photonic crystal slab waveguides, we show the importance of Bloch mode reshaping and multiple scattering. We describe a convenient and fully three-dimensional theoretical treatment of disorder-induced extrinsic scattering, including the calculation of backscatter and out-of-plane losses per unit cell, and the extrapolation of the unit-cell loss to the loss for an entire disordered waveguide. The theoretical predictions, which are also compared with recent measurements on dispersion engineered silicon waveguides, demonstrate the failure of the Beer-Lambert law due to multiple scattering. We also explain why the previously assumed group velocity scalings of disorder-induced loss break down in general.

  17. Multiple Family Group Service Model for Children With Disruptive Behavior Disorders: Child Outcomes at Post-Treatment.

    Science.gov (United States)

    Chacko, Anil; Gopalan, Geetha; Franco, Lydia; Dean-Assael, Kara; Jackson, Jerrold; Marcus, Sue; Hoagwood, Kimberly; McKay, Mary

    2015-06-01

    The purpose of this study was to determine the benefits of a multiple family group (MFG) service delivery model compared with services as usual (SAU) in improving the functioning of youth with oppositional defiant/conduct disorder in families residing in socioeconomically disadvantaged communities. Participants included 320 youth aged 7 to 11 and their families who were referred to participating outpatient clinics. Participants were assigned to the MFG or the SAU condition, with parent report of child oppositional behavior, social competence, and level of youth impairment as primary outcomes at post-treatment. Family engagement to MFG was measured by attendance to each group session. Caregivers of youth in the MFG service delivery model condition reported significant improvement in youth oppositional behavior and social competence compared with youth in the SAU condition. Impairment improved over time for both groups with no difference between treatment conditions. The MFG led to greater percentage of youth with clinically significant improvements in oppositional behavior. Attendance to the MFG was high, given the high-risk nature of the study population. The MFG service delivery model offers an efficient and engaging format to implement evidence-based approaches to improving functioning of youth with oppositional defiant and/or conduct disorder in families from socioeconomically disadvantaged communities.

  18. Characteristics of multiple sclerosis patient stance control disorders, measured by means of posturography and related to brainstem lesions

    Directory of Open Access Journals (Sweden)

    Dario Alpini

    2012-01-01

    Full Text Available Balance disorders are commonly observed during the course of multiple sclerosis (MS. The aim of this study is to report characteristics of MS patient stance control disorders, measured by means of posturography and related to the brainstem lesions. Thirty-eight patients affected by MS, mildly to moderately disable according to Kurtzke’s Expanded Disability Status Scale, underwent a complete clinical neurological and vestibular evaluation and brain MRI scanning. All patients were then tested on a static posturography platform (Tetrax, Israel in four conditions: eyes open and eyes closed standing on a firm surface and on a foam pad. Clinical and/or magnetic resonance imaging evidence of brainstem involvement was observed in 55.3% of patients. When brainstem lesion was detected, Fourier analysis showed a typical pattern characterized by inversion of the 0- 0.1 Hz and 0.1-0.25 Hz frequency bands. In conclusion, MS leads to pervasive postural disturbances in the majority of subjects, including the visuo-vestibular loops and proprioception involving vestibulospinal pathways in at least 55.3% of patients. Our results may also suggest the presence of Fourier inversion in patients with brainstem lesions.

  19. Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Claire S Leblond

    2012-02-01

    Full Text Available Autism spectrum disorders (ASD are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls. We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4% patients and in 16 of 1,090 (1.5% controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70. In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013. Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

  20. Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

    Science.gov (United States)

    Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I. Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemière, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P.; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A.; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M.; Poustka, Fritz; Freitag, Christine M.; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F.; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W.; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M.; Bourgeron, Thomas

    2012-01-01

    Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. PMID:22346768

  1. Sudden hearing loss as the initial symptom in Japanese patients with multiple sclerosis and seropositive neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Tanaka, Masami; Tanaka, Keiko

    2016-09-15

    Sudden hearing loss may occur in rare cases of relapsing-remitting multiple sclerosis (RRMS). There have also been reports of idiopathic sudden sensorineural hearing loss (SNHL) in patients with neuromyelitis optica spectrum disorders (NMOSD), but the frequency of such cases is unclear. We conducted a retrospective analysis of the medical records of 173 consecutive patients with multiple sclerosis (MS) and 101 consecutive patients with NMOSD who tested positive for anti-aquaporin-4 antibodies in addition to 37 consecutive patients with clinically isolated syndromes (CIS) to investigate the frequency and onset timing of SNHL. SNHL was observed in six (3.5%) of the RRMS cases, one (1.0%) of the seropositive NMOSD cases, and three (8.1%) of the CIS cases. SNHL occurred ahead of onset in 4/6 MS patients and in all of 3 CIS patients. Patient with NMOSD exhibited SNHL 6years after the onset of NMOSD. Although SNHL is rare, these results suggest the risk of developing demyelinating lesions in the central nervous system and further conversion to MS in the future. Copyright © 2016. Published by Elsevier B.V.

  2. Multiple patterns of writing disorders in dementia of the Alzheimer type and their evolution.

    Science.gov (United States)

    Luzzatti, Claudio; Laiacona, Marcella; Agazzi, Daniela

    2003-01-01

    This paper reports the results obtained from a writing task given to 23 Italian patients suffering from mild to moderate dementia of the Alzheimer's type (DAT). Spelling performance was tested with a task that taps the sub-word-level (spelling of regular words and nonwords), and the lexical route (spelling of regular and irregular words), in line with contemporary models of writing. Each patient's performance was classified according to the emergence of dissociated patterns of damage between regular words and nonwords and between regular and irregular words. The 23 DAT patients span the whole spectrum of dysgraphic taxonomy; five showed the characteristic pattern of impairment of surface dysgraphia, two showed the characteristics of phonological dysgraphia, while a mixed pattern (i.e. better performance on regular words compared to irregular words and regular nonwords) emerged in seven cases. Three patients presented undifferentiated writing disorders, two were completely agraphic, while four patients showed only minimal or no writing defects. The rate of dissociated impairments in the lexical and the sub-word-level routine is very similar to that observed after acute focal brain damage, which contradicts the hypothesis that degenerative brain damage selectively impairs writing performance along the lexical-semantic route. To test the hypothesis that surface sub-word-level processing abilities are affected only during the evolution of the disease, nine patients were tested longitudinally after an interval of 6-12 months. Once again, the data showed high variability across subjects, and do not seem to support involvement of the sub-word-level spelling routine only at a late stage in the development of the disease.

  3. Post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation: a single-center experience.

    Science.gov (United States)

    Luo, Lan; Zhang, Lin; Cai, Bo; Li, Honghua; Huang, Wenrong; Jing, Yu; Zhu, Haiyan; Zhao, Yu; Bo, Jian; Wang, Quanshun; Han, Xiaoping; Yu, Li; Gao, Chunji

    2014-01-08

    Post-transplant lymphoproliferative disease (PTLD) is a rare and serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or solid organ transplantation. We conducted a retrospective analysis of the occurrence of post-transplant lymphoproliferative disease in allo-HSCT recipients over 12 years in a single center in China. A total of 343 patients received allo-HSCT. The conditioning therapy consisted of a busulfan/cyclophosphamide-based regimen, a fludarabine/cyclophosphamide-based regimen, or total-body irradiation and cyclophosphamide. In transplantations from unrelated donors and haplo-identical donors, patients also received antithymocyte globulin (ATG) or thymoglobulin as part of the conditioning. Five of the 343 patients (1.46%) were diagnosed with PTLD and all 5 were given ATG as part of conditioning. Among these 5 patients, 4 had lymphoid neoplasm before transplantation. EBV-positivity was confirmed in 4 patients. All 5 PTLD patients received reduction of immunosuppression (RI) as fundamental therapy. At follow-up on April 1, 2013, 1 patient had survived for 2 years and 1 had survived for 9 years. The correlation of PTLD with ATG and underlying diseases were examined by statistical analysis using the chi-squared test or Fisher's exact test (P=0.011 and 0.025, respectively). Although only 1.46% of patients progressed to PTLD associated with ATG and underlying diseases, the mortality was still high. Moreover, RI can be an effective therapy for PTLD patients, but other approaches should be further explored.

  4. Hypogelsolinemia, a disorder of the extracellular actin scavenger system, in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Janmey Paul A

    2010-11-01

    Full Text Available Abstract Background Extracellular gelsolin (GSN and GC-globulin/Vitamin D-binding protein (DBP appear to play an important role in clearing the actin from extracellular fluids and in modulating cellular responses to anionic bioactive lipids. In this study we hypothesized that cellular actin release and/or increase in bioactive lipids associated with multiple sclerosis (MS development will translate into alteration of the actin scavenger system protein concentrations in blood and cerebrospinal fluid (CSF of patients with MS. Methods We measured GSN and DBP concentrations in blood and CSF obtained from patients diagnosed with MS (n = 56 in comparison to a control group (n = 20 that includes patients diagnosed with conditions such as idiopathic cephalgia (n = 11, idiopathic (Bell's facial nerve palsy (n = 7 and ischialgia due to discopathy (n = 2. GSN and DBP levels were measured by Western blot and ELISA, respectively. Results We found that the GSN concentration in the blood of the MS group (115 ± 78 μg/ml was significantly lower (p Conclusions The decrease of GSN concentration in blood and CSF of MS subjects suggests that this protein may be involved in chronic inflammation associated with neurodegeneration. Additionally, the results presented here suggest the possible utility of GSN evaluation for diagnostic purposes. Reversing plasma GSN deficiency might represent a new strategy in MS treatment.

  5. Multiple traumatisation as a risk factor of post-traumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Savjak Nadežda

    2003-01-01

    Full Text Available Paper presents a part of results obtained in 1998 within action study of the psychological effects of war traumatisation in Republika Srpska. Special attention is paid to the additional impact of multiple exposure to war sufferings regarding the degree of the traumatisation (the loss of loved ones, direct life threat, the participation in combats, and the testimony of the death of other people. 229 persons were assessed in 8 towns of Republika Srpska. The comparison of the results of refugees and domicile persons at the Reaction Index - Revised speaks in favour of their significantly higher vulnerability even after three years after the end of war. Total degree of the traumatisation, as well as the symptoms of intrusion, avoidance, and hyper-arousal are significantly more frequent. In 42.5% of refugees (in relation to 26.7% of domicile persons there is PTSP risk. The intensification of criteria proves that 17% of refugees are at high risk (in relation to 5.2% of the domiciled. It is obvious, that refuge presents traumatic event for many people, and not only chronic burden. The results suggest that the effect of direct jeopardy, combat stress, and the testimony of somebody else’s death are fading in time, but that the culmination of tangible, social, and human losses in refuge is serious risk factor for mental health.

  6. [Contribution of cognitive evoked potentials for detecting early cognitive disorders in multiple sclerosis].

    Science.gov (United States)

    Magnié, M N; Bensa, C; Laloux, L; Bertogliati, C; Faure, S; Lebrun, C

    2007-11-01

    In Multiple Sclerosis (MS), one of the most frequent neurological diseases in young adults, cognitive dysfunctions have been under considered whereas their evolution may produce a fronto-sous-cortical deterioration and more than half of the MS patients present such dysfunctions. Nevertheless sensory evoked-potentials are classically used in this disease, event-related potentials (ERP) are not included in the clinical exploration of MS. Two studies are presented aimed at further tracking the usefulness of ERP for detecting early cognitive dysfunctions in MS. All of the patients presented a relapsing remitting MS for less than 5 years with a moderate physical handicap and complained from their memory. They performed a neuropsychological set and ERP were elicited using the oddball paradigm in both modalities, visual and auditory. In the first study, 10 patients without cognitive dysfunction at the neuropsychological evaluation and 10 patients with an attention deficit participated with 10 age-matched controls. In the second study, 10 patients with memory impairment at the neuropsychological evaluation and 10 age-matched controls were included. Our data argue for an earlier modification of ERP parameters in the visual modality than in the auditory one, even before the modification of cognitive scores. In both studies, P300 parameters were correlated to neuropsychological performances (and especially to the attention examination in the first study and to memory tests in the second study) in both modalities. Taking into account the clinical usefulness of ERPs, it is nowadays important to include this electrophysiological method in evaluation and follow-up of MS, and not only using the auditory modality but also the visual presentation in order to detect earlier cognitive dysfunctions even before modification of neuropsychological performances.

  7. Possibilities of pharmacologic correction of cognitive disorders in conditions of experimental equivalent of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Nefyodov A.A.

    2015-06-01

    Full Text Available A comparative analysis of the impact of citicoline, ±-lipoic acid, nicergoline, donepezil and colloidal solution of nano-silver (CSNS on the processes of learning and consolidation of memorable track in the test of the conditional reaction of passive avoidance (CRPA in conditions of experimental allergic encephalomyelitis (EAE was conducted. Testing of passive defensive skill was performed on days 12 and 20 after the induction of EAE. To assess the impact of drugs on the inputted information processes the investigated substances were administered intragastrically (CSNS - intraperitoneally once daily in the definite dose from the second to the day 10 after the induction of EAE (latent phase of the disease, and assessing processes of conditional skill preserving, further administration of drugs by the day 20 of the experiment (average duration of EAE was used. A positive effect of citicoline, ±-lipoic acid, nicergoline and donepezil on the input information processes and the ability to prevent accelerated extinction of acquired contingent skill in the conditions of experimental pathology was established. Drugs statistically significantly increased duration of the latent period of CRPA in comparison with a group of active control by 49%, 43%, 39% and 34%, respectively. Here with preparations were characterized by a high coefficient of antiamnesic activity, by the end of the experiment it was recorded at the level of 95% (citicoline, 81% (±-lipoic acid, 76% (nicergoline and 53% (donepezil. It is shown that the ability to prevent development of cognitive impairment in conditions of experimental equivalent of multiple sclerosis decreases in the number of citicoline (500 mg/kg > ±-lipoic acid (50 mg/kg H nicergoline (10 mg/kg > donepezil (10 mg/kg.

  8. Karyotypic abnormalities and clinical aspects of patients with multiple myeloma and related paraproteinemic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Liang, W.; Hopper, J.E.; Rowley, J.D.

    1979-08-01

    Karyotypic abnormalities were detected in the malignant cells of 6 of 18 patients with multiple myeloma (MM). Six patients with benign monoclonal gammopathy, one with amyloidosis of immunoglobulin origin, and two with Waldenstroem's macroglobulinemia had normal karyotypes. All six MM patients with aneuploidy were in a group of 10 patients in an accelerated or relapse phase of their disease and four had high serum paraprotein levels when their abnormal karyotypes were detected. Five of the 6 MM patients with aneuploidy had received prior chemotherapy. Aneuploidy was not observed in 8 stable MM patients. Abnormalities of chromosome 14 were present in all 6 patients. A translocation between Nos. 11 and 14 was found in aneuploid cells of 2 patients who had plasma cell leukemia (PCL). A deletion of chromosome 6 was detected in 2 MM patients and a pericentric inversion of No. 6 was seen in the patient with PCL. Three of 4 MM patients had a nonrandom loss of one chromosome 8. Two other MM patients developed acute nonlymphocytic leukemia (ANLL) after the diagnosis of MM. Marrow cells of one patient showed a 5q- chromosome and a constitutional translocation involving Nos. 13 and 14 during the preleukemic stage; during the leukemic phase, the karyotype evolved to 50 chromosomes including extra chromosomes 1, 6, 8, 10, and 21 and a missing 7, in addition to the originally detected 5q- and the 13/14 translocation.The peripheral blood from the other patient was hypodiploid, with a missing chromosome 7 and a translocation between 3q and 9p. These patterns of chromosome change resemble those of ANLL rather than MM and are similar to the changes seen in ANLL after treated malignant lymphoma.

  9. A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder

    Science.gov (United States)

    Lam, Juleen; Sutton, Patrice; Kalkbrenner, Amy; Windham, Gayle; Halladay, Alycia; Koustas, Erica; Lawler, Cindy; Davidson, Lisette; Daniels, Natalyn; Newschaffer, Craig; Woodruff, Tracey

    2016-01-01

    Background Exposure to ambient air pollution is widespread and may be detrimental to human brain development and a potential risk factor for Autism Spectrum Disorder (ASD). We conducted a systematic review of the human evidence on the relationship between ASD and exposure to all airborne pollutants, including particulate matter air pollutants and others (e.g. pesticides and metals). Objective To answer the question: “is developmental exposure to air pollution associated with ASD?” Methods We conducted a comprehensive search of the literature, identified relevant studies using inclusion/exclusion criteria pre-specified in our protocol (registered in PROSPERO, CRD # 42015017890), evaluated the potential risk of bias for each included study and identified an appropriate subset of studies to combine in a meta-analysis. We then rated the overall quality and strength of the evidence collectively across all air pollutants. Results Of 1,158 total references identified, 23 human studies met our inclusion criteria (17 case-control, 4 ecological, 2 cohort). Risk of bias was generally low across studies for most domains; study limitations were related to potential confounding and accuracy of exposure assessment methods. We rated the quality of the body of evidence across all air pollutants as “moderate.” From our meta-analysis, we found statistically significant summary odds ratios (ORs) of 1.07 (95% CI: 1.06, 1.08) per 10-μg/m3 increase in PM10 exposure (n = 6 studies) and 2.32 (95% CI: 2.15, 2.51) per 10-μg/m3 increase in PM2.5 exposure (n = 3 studies). For pollutants not included in a meta-analysis, we collectively evaluated evidence from each study in rating the strength and quality of overall evidence considering factors such as inconsistency, imprecision, and evidence of dose-response. All included studies generally showed increased risk of ASD with increasing exposure to air pollution, although not consistently across all chemical components. Conclusion After

  10. Multiple comorbidities of 21 psychological disorders and relationships with psychosocial variables: a study of the online assessment and diagnostic system within a web-based population.

    Science.gov (United States)

    Al-Asadi, Ali M; Klein, Britt; Meyer, Denny

    2015-02-26

    While research in the area of e-mental health has received considerable attention over the last decade, there are still many areas that have not been addressed. One such area is the comorbidity of psychological disorders in a Web-based sample using online assessment and diagnostic tools, and the relationships between comorbidities and psychosocial variables. We aimed to identify comorbidities of psychological disorders of an online sample using an online diagnostic tool. Based on diagnoses made by an automated online assessment and diagnostic system administered to a large group of online participants, multiple comorbidities (co-occurrences) of 21 psychological disorders for males and females were identified. We examined the relationships between dyadic comorbidities of anxiety and depressive disorders and the psychosocial variables sex, age, suicidal ideation, social support, and quality of life. An online complex algorithm based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision, was used to assign primary and secondary diagnoses of 21 psychological disorders to 12,665 online participants. The frequency of co-occurrences of psychological disorders for males and females were calculated for all disorders. A series of hierarchical loglinear analyses were performed to examine the relationships between the dyadic comorbidities of depression and various anxiety disorders and the variables suicidal ideation, social support, quality of life, sex, and age. A 21-by-21 frequency of co-occurrences of psychological disorders matrix revealed the presence of multiple significant dyadic comorbidities for males and females. Also, for those with some of the dyadic depression and the anxiety disorders, the odds for having suicidal ideation, reporting inadequate social support, and poorer quality of life increased for those with two-disorder comorbidity than for those with only one of the same two disorders. Comorbidities of

  11. Multiple Comorbidities of 21 Psychological Disorders and Relationships With Psychosocial Variables: A Study of the Online Assessment and Diagnostic System Within a Web-Based Population

    Science.gov (United States)

    Klein, Britt; Meyer, Denny

    2015-01-01

    Background While research in the area of e-mental health has received considerable attention over the last decade, there are still many areas that have not been addressed. One such area is the comorbidity of psychological disorders in a Web-based sample using online assessment and diagnostic tools, and the relationships between comorbidities and psychosocial variables. Objective We aimed to identify comorbidities of psychological disorders of an online sample using an online diagnostic tool. Based on diagnoses made by an automated online assessment and diagnostic system administered to a large group of online participants, multiple comorbidities (co-occurrences) of 21 psychological disorders for males and females were identified. We examined the relationships between dyadic comorbidities of anxiety and depressive disorders and the psychosocial variables sex, age, suicidal ideation, social support, and quality of life. Methods An online complex algorithm based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision, was used to assign primary and secondary diagnoses of 21 psychological disorders to 12,665 online participants. The frequency of co-occurrences of psychological disorders for males and females were calculated for all disorders. A series of hierarchical loglinear analyses were performed to examine the relationships between the dyadic comorbidities of depression and various anxiety disorders and the variables suicidal ideation, social support, quality of life, sex, and age. Results A 21-by-21 frequency of co-occurrences of psychological disorders matrix revealed the presence of multiple significant dyadic comorbidities for males and females. Also, for those with some of the dyadic depression and the anxiety disorders, the odds for having suicidal ideation, reporting inadequate social support, and poorer quality of life increased for those with two-disorder comorbidity than for those with only one of the same

  12. Autoimmune lymphoproliferative syndrome in a patient with a new minimal deletion in the death domain of the FAS gene

    NARCIS (Netherlands)

    Gualco, Gabrieta; van den Berg, Anke; Koopmans, Sicco; Bacchi, Livia M.; Carneiro, Siderley S.; Ruiz, Everaldo; Vecchi, Ana Paula; Chan, John K. C.

    2008-01-01

    We present a case of autoimmune lymphoproliferative syndrome (ALPS) caused by a previously undescribed minimal deletion in the death domain of the FAS gene. ALPS is an uncommon disease associated with an impaired Fas-mediated apoptosis. The patient presented with a history of splenomegaly since 4 mo

  13. Extreme lymphoproliferative disease and fatal autoimmune thrombocytopenia in FasL and TRAIL double-deficient mice.

    Science.gov (United States)

    Sedger, Lisa M; Katewa, Arna; Pettersen, Ann K; Osvath, Sarah R; Farrell, Geoff C; Stewart, Graeme J; Bendall, Linda J; Alexander, Stephen I

    2010-04-22

    To delineate the relative roles of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand in lymphocyte biology and lymphoproliferative disease, we generated mice defective in both molecules. B6.GT mice develop severe polyclonal lymphoproliferative disease because of accumulating CD3(+)CD4(-)CD8(-)B220(+) T cells, CD4(+) and CD8(+) T cells, and follicular B cells, and mice die prematurely from extreme lymphocytosis, thrombocytopenia, and hemorrhage. Accumulating lymphocytes resembled antigen-experienced lymphocytes, consistent with the maximal resistance of B6.GT CD4(+) and CD8(+) T cell to activation-induced cell death. More specifically, we show that TRAIL contributes to Fas ligand-mediated activation-induced cell death and controls lymphocyte apoptosis in the presence of interferon-gamma once antigen stimulation is removed. Furthermore, dysregulated lymphocyte homeostasis results in the production of anti-DNA and rheumatoid factor autoantibodies, as well as antiplatelet IgM and IgG causing thrombocytopenia. Thus, B6.GT mice reveal new roles for TRAIL in lymphocyte homeostasis and autoimmune lymphoproliferative syndromes and are a model of spontaneous idiopathic thrombocytopenia purpura secondary to lymphoproliferative disease.

  14. The role of noradrenergic nerves in the development of the lymphoproliferative disease in fas-deficient, lpr/lpr mice

    NARCIS (Netherlands)

    del Rey, A; Roggero, E; Kabiersch, A; Schafer, M; Besedovsky, HO

    2006-01-01

    Lp/lpr mice develop a lymphoproliferative, autoimmune, lupus-like disease. These mice lack functional Fas (CD95) expression and are resistant to Fas ligand (CD 178)-mediated apoptosis, a critical mechanism for the maintenance of peripheral tolerance. In this study, we show that noradrenaline (NA), t

  15. Posterior reversible encephalopathy syndrome in a child with autoimmune lymphoproliferative syndrome: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Vaishnavi Chandramohan

    2012-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is characterized by headache, nausea, vomiting, seizures and visual disturbances. PRES has been usually associated with hypertension, chronic renal disease, malignancy and chemotherapeutic agents. We report the association of PRES with Autoimmune lymphoproliferative syndrome, which to our best knowledge has not been reported before.

  16. Family history of education predicts eating disorders across multiple generations among 2 million Swedish males and females.

    Directory of Open Access Journals (Sweden)

    Anna Goodman

    Full Text Available To investigate which facets of parent and grandparent socio-economic position (SEP are associated with eating disorders (ED, and how this varies by ED subtype and over time.Total-population cohort study of 1,040,165 females and 1,098,188 males born 1973-1998 in Sweden, and followed for inpatient or outpatient ED diagnoses until 2010. Proportional hazards models estimated associations with parental education, income and social class, and with grandparental education and income.15,747 females and 1051 males in our sample received an ED diagnosis, with rates increasing in both sexes over time. ED incidence in females was independently predicted by greater educational level among the father, mother and maternal grandparents, but parent social class and parental income showed little or no independent effect. The associations with education were equally strong for anorexia nervosa, bulimia nervosa and ED not-otherwise-specified, and had increased over time. Among males, an apparently similar pattern was seen with respect to anorexia nervosa, but non-anorexia ED showed no association with parental education and an inverse association with parental income.Family history of education predicts ED in gender- and disorder-specific ways, and in females the effect is observed across multiple generations. Particularly given that these effects may have grown stronger in more recent cohorts, these findings highlight the need for further research to clarify the underlying mechanisms and identify promising targets for prevention. Speculatively, one such mechanism may involve greater internal and external demands for academic success in highly educated families.

  17. 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.

    Science.gov (United States)

    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.

  18. Impact of childhood exposure to psychological trauma on the risk of psychiatric disorders and somatic discomfort: single vs. multiple types of psychological trauma.

    Science.gov (United States)

    Park, Subin; Hong, Jin Pyo; Bae, Jae Nam; Cho, Seong-Jin; Lee, Dong-Woo; Lee, Jun-Young; Chang, Sung Man; Jeon, Hong Jin; Hahm, Bong-Jin; Lee, Young Moon; Seong, Sujeong; Cho, Maeng Je

    2014-11-30

    We examined whether childhood exposure to multiple types of potentially traumatic events (PTEs) relative to a single type of PTE is associated with a higher prevalence of psychiatric disorders and greater somatic discomfort in Korean adults. The Composite International Diagnostic Interview 2.1 (K-CIDI 2.1) was administered to 6027 subjects aged 18-74 years. Subjects who experienced a traumatic event before the age of 18 years, the childhood trauma exposure group, were compared with controls without childhood exposure to PTEs. In the childhood trauma exposure group, subjects who experienced only a single type of PTE and subjects who experienced two or more types of PTEs were compared further. Childhood exposure to PTEs was linked to a wide range of psychiatric comorbidities, with a higher risk for exposure to multiple types of PTEs than for exposure to a single type of PTE. Obsessive-compulsive disorder, generalized anxiety disorder, and somatoform disorder were significantly associated with exposure to multiple types of PTEs but not with exposure to a single type of PTE. Exposure to multiple types of PTEs was associated with reports of marked fatigue and pain. Future research should examine the psychiatric sequelae associated with various types of childhood PTEs. Copyright © 2014. Published by Elsevier Ireland Ltd.

  19. The Diagnostic Drawing Series and the Tree Rating Scale: An Isomorphic Representation of Multiple Personality Disorder, Major Depression, and Schizophrenic Populations.

    Science.gov (United States)

    Morris, Maureen Batza

    1995-01-01

    The tree drawings of 80 subjects, who were diagnosed with either multiple personality disorder, schizophrenia, or major depression, and a control group, were rated. Patterns were examined and graphs were used to depict results. Certain features were found to distinguish each category. The descriptive statistical findings were both consistent and…

  20. Predicting Social and Communicative Ability in School-Age Children with Autism Spectrum Disorder: A Pilot Study of the Social Attribution Task, Multiple Choice

    Science.gov (United States)

    Burger-Caplan, Rebecca; Saulnier, Celine; Jones, Warren; Klin, Ami

    2016-01-01

    The Social Attribution Task, Multiple Choice is introduced as a measure of implicit social cognitive ability in children, addressing a key challenge in quantification of social cognitive function in autism spectrum disorder, whereby individuals can often be successful in explicit social scenarios, despite marked social adaptive deficits. The…

  1. The Diagnostic Drawing Series and the Tree Rating Scale: An Isomorphic Representation of Multiple Personality Disorder, Major Depression, and Schizophrenic Populations.

    Science.gov (United States)

    Morris, Maureen Batza

    1995-01-01

    The tree drawings of 80 subjects, who were diagnosed with either multiple personality disorder, schizophrenia, or major depression, and a control group, were rated. Patterns were examined and graphs were used to depict results. Certain features were found to distinguish each category. The descriptive statistical findings were both consistent and…

  2. Patients with schizophrenia or schizoaffective disorder who receive multiple electroconvulsive therapy sessions: characteristics, indications, and results

    Directory of Open Access Journals (Sweden)

    Iancu I

    2015-03-01

    Full Text Available Iulian Iancu,* Nimrod Pick,* Orit Seener-Lorsh, Pinhas Dannon Be’er Ya’akov Mental Health Center, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel *These authors share first authorship of this paper Background: While electroconvulsive therapy (ECT has been used for many years, there is insufficient research regarding the indications for continuation/maintenance (C/M-ECT, its safety and efficacy, and the characteristics of patients with schizophrenia or schizoaffective disorder who receive multiple ECT sessions. The aims of this study were to characterize a series of patients who received 30 ECT sessions or more, to describe treatment regimens in actual practice, and to examine the results of C/M-ECT in terms of safety and efficacy, especially the effect on aggression and functioning.Methods: We performed a retrospective chart review of 20 consecutive patients (mean age 64.6 years with schizophrenia (n=16 or schizoaffective disorder (n=4 who received at least 30 ECT sessions at our ECT unit, and also interviewed the treating physician and filled out the Clinical Global Impression-Severity, Global Assessment of Functioning, and the Staff Observation Aggression Scale-Revised.Results: Patients received a mean of 91.3 ECT sessions at a mean interval of 2.6 weeks. All had been hospitalized for most or all of the previous 3 years. There were no major adverse effects, and cognitive side effects were relatively minimal (cognitive deficit present for several hours after treatment. We found that ECT significantly reduced scores on the Staff Observation Aggression Scale-Revised subscales for verbal aggression and self-harm, and improved Global Assessment of Functioning scores. There were reductions in total aggression scores, subscale scores for harm to objects and to others, and Clinical Global Impression-Severity scores, these were not statistically significant.Conclusion: C/M-ECT is safe and effective for

  3. Collaborative Care for patients with severe borderline and NOS personality disorders: A comparative multiple case study on processes and outcomes

    Directory of Open Access Journals (Sweden)

    Koekkoek Bauke

    2011-06-01

    Full Text Available Abstract Background Structured psychotherapy is recommended as the preferred treatment of personality disorders. A substantial group of patients, however, has no access to these therapies or does not benefit. For those patients who have no (longer access to psychotherapy a Collaborative Care Program (CCP is developed. Collaborative Care originated in somatic health care to increase shared decision making and to enhance self management skills of chronic patients. Nurses have a prominent position in CCP's as they are responsible for optimal continuity and coordination of care. The aim of the CCP is to improve quality of life and self management skills, and reduce destructive behaviour and other manifestations of the personality disorder. Methods/design Quantitative and qualitative data are combined in a comparative multiple case study. This makes it possible to test the feasibility of the CCP, and also provides insight into the preliminary outcomes of CCP. Two treatment conditions will be compared, one in which the CCP is provided, the other in which Care as Usual is offered. In both conditions 16 patients will be included. The perspectives of patients, their informal carers and nurses are integrated in this study. Data (questionnaires, documents, and interviews will be collected among these three groups of participants. The process of treatment and care within both research conditions is described with qualitative research methods. Additional quantitative data provide insight in the preliminary results of the CCP compared to CAU. With a stepped analysis plan the 'black box' of the application of the program will be revealed in order to understand which characteristics and influencing factors are indicative for positive or negative outcomes. Discussion The present study is, as to the best of our knowledge, the first to examine Collaborative Care for patients with severe personality disorders receiving outpatient mental health care. With the chosen

  4. The potential use of adult stem cells for the treatment of multiple sclerosis and other neurodegenerative disorders.

    Science.gov (United States)

    Slavin, Shimon; Kurkalli, Basan G S; Karussis, Dimitrios

    2008-11-01

    No specific treatment exists for patients with multiple sclerosis (MS) who fail to respond to conventional immunosuppressive and immunomodulating modalities. Furthermore, no method is available for regeneration of existing defect in the central nervous system (CNS). The ultimate goals of MS treatment, similarly to other autoimmune diseases, are twofold: first, to eliminate self-reactive lymphocytes and to prevent de novo development of self-reactivity by induction of self-tolerance. Second, attempting regeneration and repair of existing damage. In the case of MS, there is a need to stop the ongoing process of inflammation against the CNS by self-reactive lymphocytes thus facilitating spontaneous re-myelinization while in parallel attempt to recover existing neurological deficits caused by the autoimmune process resulting in demyelinization. Cell therapy stands out as the most rationale approach for neurological regeneration. In the absence of clinically applicable approaches involving the use of embryonic stem cells, we are investigating the feasibility and efficacy of enriched autologous mesenchymal stromal cells (MSC) injected intrathecally and intravenously to induce in situ immunomodulation and neuroprotection and possibly facilitate repair of the CNS in patients with MS and other neurodegenerative disorders. Our preclinical results suggest that bone marrow cells may provide a source of stem cells with a potential for migration into inflamed CNS and differentiate into cells expressing neuronal and glial cell markers. Based on the preclinical data, we are currently evaluating the safety of a similar therapeutic approach in a small group of patients with MS and other neurodegenerative diseases.

  5. Prevalence and significant determinants of post-traumatic stress disorder in a large sample of patients with multiple sclerosis.

    Science.gov (United States)

    Ostacoli, Luca; Carletto, Sara; Borghi, Martina; Cavallo, Marco; Rocci, Emanuela; Zuffranieri, Marco; Malucchi, Simona; Bertolotto, Antonio; Zennaro, Alessandro; Furlan, Pier Maria; Picci, Rocco Luigi

    2013-06-01

    Chronic and life-threatening neurodegenerative diseases may be associated with post-traumatic stress disorder (PTSD). Therefore, the current study was an investigation of the prevalence of PTSD in multiple sclerosis (MS) patients, and identification of significant determinants of PTSD. Two hundred thirty-two MS patients were consecutively recruited and screened for the presence of PTSD with the Impact of Event Scale-Revised, corroborated by the Structured Clinical Interview for DSM-IV. Furthermore, participants were administered the Hospital Anxiety and Depression Scale and the Fatigue Severity Scale. Twelve patients (12/232, i.e. 5.17 %) were diagnosed as suffering from PTSD. Levels of education, anxiety and depression were significant determinants of the presence of PTSD. The role played by the levels of education, anxiety and depression in determining the presence of PTSD has been discussed. Further research on the psychological features of neurodegenerative diseases is urgently needed in order to plan appropriate treatments and improve patients' quality of life.

  6. Increases in multiple psychiatric disorders in parents and grandparents of patients with bipolar disorder from the USA compared with The Netherlands and Germany

    NARCIS (Netherlands)

    Post, Robert M.; Leverich, Gabriele S.; Kupka, Ralph; Keck, Paul E.; McElroy, Susan L.; Altshuler, Lori L.; Frye, Mark A.; Rowe, Michael; Grunze, Heinz; Suppes, Trisha; Nolen, Willem A.

    2015-01-01

    ObjectiveWe previously found that compared with Europe more parents of the USA patients were positive for a mood disorder, and that this was associated with early onset bipolar disorder. Here we examine family history of psychiatric illness in more detail across several generations.MethodsA total of

  7. Trisomy 12 is seen within a specific subtype of B-cell chronic lymphoproliferative disease affecting the peripheral blood/bone marrow and co-segregates with elevated expression of CD11a.

    Science.gov (United States)

    Su'ut, L; O'Connor, S J; Richards, S J; Jones, R A; Roberts, B E; Davies, F E; Fegan, C D; Jack, A S; Morgan, G J

    1998-04-01

    In order to delineate the specific morphological and immunophenotypic features of B-cell lymphoproliferative disorders associated with trisomy 12, 172 sequential unselected cases of CD19+CD5+ B-cell disorders, primarily affecting the peripheral blood and bone marrow, were studied. Trisomy 12 was found in 24 cases (13.9%), with all cases morphologically classified as either CLL-PL or CLL-mixed by FAB criteria. Trisomy 12 was not found in any cases of typical CLL. Trisomy 12 cases demonstrated a significant higher expression of CD11a (P<0.0001) and CD20 (P<0.0006) when compared to cases with the equivalent morphology and immunophenotype, but without the chromosomal abnormality. Trisomy 12 cases also demonstrated a higher frequency of FMC7, CD38 expression and moderate to strong surface immunoglobulin staining. However, no correlation was detected between the percentages of trisomy 12 cells and cells expressing CD11a, CD38, FMC7 or sIg mean fluorescent intensity. Cells from trisomy 12 positive cases were sorted according to their CD11a expression using fluorescent activated cell sorting. There was a significant increase in the percentage of trisomy 12 cells within the CD11a+ sorted fraction compared to the unsorted population (P < 0.05), implying that trisomy 12 is associated with increased expression of CD11a. With the highly specific morphological and immunophenotypic features demonstrated by trisomy 12 cases in this study, it is highly likely that these cases constitute a specific group of B-cell lymphoproliferative disorders.

  8. [Monoclonal gammopathy of undetermined significance and asymptomatic multiple myelom in the year 2014 ].

    Science.gov (United States)

    Adam, Zdeněk; Krejčí, Marta; Pour, Luděk; Sevčíková, Eva; Křivanová, Andrea; Rehák, Zdeněk; Koukalová, Renata; Cermáková, Zdeňka; Vaníček, Jíří; Sevčíková, Sabina

    2014-10-01

    Presence of monoclonal immunoglobulin in serum or urine is a relatively common event affecting about 3.2 % of people over 50. Isolated increase of only one type of free light chain, either κ or λ, is detected in 0.7-0.8 % of people over 50. Most people with monoclonal immunoglobulin meet the criteria of the so-called "mono-clonal gammopathy of undetermined significance (MGUS)". MGUS is defined by concentration of monoclonal immunoglobulin in serum < 30 g/l, number of plasma cells in the bone marrow < 10 % and the absence of symptoms of multiple myeloma and other lymphoproliferative diseases. A proportion of people with MGUS gradually progresses from asymptomatic into symptomatic myeloma or other malignant lymphoproliferative disease requiring treatment. Therefore, MGUS is considered to be one of the most common premalignant conditions with an average risk of transformation into malignant disease of 1 % per year. Monoclonal gammopathy of IgG and IgA subtype can develop into multiple myeloma. Light chain monoclonal gammopathy can develop not only into light chain multiple myeloma but also into AL-amyloidosis and light chain deposition disease (amorphous deposits of light chains damaging organs). IgM monoclonal gammopathy may develop into Waldenstrom macroglobulinemia or other lymphoproliferative disorder, or into rare IgM subtype of multiple myeloma. Unfortunately, people with MGUS are threatened by more than an increased risk of transformation into multiple myeloma or other severe hematologic disease. Pre-malignant clone of plasma cells in the bone marrow causes changes in the bone marrow that directly affect the person. For people with MGUS, there is an increased incidence of osteoporosis and increased fracture risk when compared to the general population. People with MGUS also have an increased risk of bacterial infections and thromboembolic complications compared with the same age population without MGUS. Clonal plasma cells, which are the basis of MGUS, may in

  9. Dominant inhibition of Fas ligand-mediated apoptosis due to a heterozygous mutation associated with autoimmune lymphoproliferative syndrome (ALPS Type Ib

    Directory of Open Access Journals (Sweden)

    McDonald Jay M

    2007-07-01

    Full Text Available Abstract Background: Autoimmune lymphoproliferative syndrome (ALPS is a disorder of lymphocyte homeostasis and immunological tolerance due primarily to genetic defects in Fas (CD95/APO-1; TNFRSF6, a cell surface receptor that regulates apoptosis and its signaling apparatus. Methods: Fas ligand gene mutations from ALPS patients were identified through cDNA and genomic DNA sequencing. Molecular and biochemical assessment of these mutant Fas ligand proteins were carried out by expressing the mutant FasL cDNA in mammalian cells and analysis its effects on Fas-mediated programmed cell death. Results: We found an ALPS patient that harbored a heterozygous A530G mutation in the FasL gene that replaced Arg with Gly at position 156 in the protein's extracellular Fas-binding region. This produced a dominant-interfering FasL protein that bound to the wild-type FasL protein and prevented it from effectively inducing apoptosis. Conclusion: Our data explain how a naturally occurring heterozygous human FasL mutation can dominantly interfere with normal FasL apoptotic function and lead to an ALPS phenotype, designated Type Ib.

  10. HLA B44 is associated with decreased severity of autoimmune lymphoproliferative syndrome in patients with CD95 defects (ALPS type Ia).

    Science.gov (United States)

    Vacek, Marla M; Schäffer, Alejandro A; Davis, Joie; Fischer, Roxanne E; Dale, Janet K; Adams, Sharon; Straus, Stephen E; Puck, Jennifer M

    2006-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis characterized by non-malignant lymphadenopathy and splenomegaly, expansion of T cells without either CD4 or CD8 surface markers, and increased incidence of autoimmune diseases and lymphoma. Most patients with ALPS have dominant, heterozygous mutations in tumor necrosis factor receptor superfamily member 6 (TNFRSF6), which encodes CD95, also known as Fas, a mediator of apoptosis. Penetrance and range of disease manifestations in ALPS are highly variable, even among family members who share the same dominant TNFRSF6 mutation. To evaluate HLA as a candidate modifier locus, we typed HLA A, B (including subtypes), and DQB alleles in 356 individuals from 63 unrelated families with defined TNFRSF6 mutations associated with ALPS. We also developed a quantitative severity score and performed statistical analysis. Among the healthier, mutation-bearing individuals, transmission of HLA B44 was significantly overrepresented (nominal PALPS. The B44 allele may exert a protective role in ALPS.

  11. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network.

    Science.gov (United States)

    van de Donk, Niels W C J; Palumbo, Antonio; Johnsen, Hans Erik; Engelhardt, Monika; Gay, Francesca; Gregersen, Henrik; Hajek, Roman; Kleber, Martina; Ludwig, Heinz; Morgan, Gareth; Musto, Pellegrino; Plesner, Torben; Sezer, Orhan; Terpos, Evangelos; Waage, Anders; Zweegman, Sonja; Einsele, Hermann; Sonneveld, Pieter; Lokhorst, Henk M

    2014-06-01

    Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance. Copyright© Ferrata Storti Foundation.

  12. Chronic lymphoproliferative diseases: survival in cohort study of 310 patients (single-center study results and literature data

    Directory of Open Access Journals (Sweden)

    V. P. Pop

    2014-01-01

    Full Text Available Introduction. Chronic lymphoproliferative disease (CLPD are common hematologic malignancies, accompanied by highly variable clinical course, different prognosis and understudied survival as one of the main criteria for long-term treatment efficacy, especially outside of clinical trials.Materials and methods. Patients with CLPD (n = 310 treated in hematology center of Burdenko Main Military Clinical Hospital from June 2003 to September 2014 are included in the study. The diagnosis of specific nosology verified in accordance with national and international recommendations. Analysis of study outcomes was based on overall survival (OS using the Kaplan–Meier method.Results and discussion. Most patients (mainly with non-Hodgkin»s lymphoma (NHL – 75 %, or multiple myeloma (MM – 80.6 % had advanced disease (III–IV, and 20.3 % admitted to the hospital in poor general condition (ECOG somatic status – 3–4. A significant proportion of patients (38.3 % with NHL and Hodgkin lymphoma (HL had a large tumor masses. Median of OS in patients with CLPD was 81.1 months. 5-year survival of total patients from time of diagnosis was 62 %, 10-year survival rate – 37 %. Patients with MM have shortest median of OS – 39 months, while patients with chronic lymphocytic leukemia (CLL have the longest – 117.8 months. Median OS for NHL patients was 68.1 months, for HL patients – 99.3 months. When comparing survival for two time intervals (2003–2009 and 2009–2014, a tendency to increasethe survival rate for certain groups of patients with CLPD was revealed, that could be due to target therapy and new therapeutic approaches.Conclusion. New drug efficacy for certain diseases has led to renewed interest in the results of CLPD therapy. In our study, most CLPD patients have long-term OS, but the subsequent therapy lines influence on OS requires further study. These results will contribute to new developments in the organization and planning of

  13. Chronic lymphoproliferative diseases: survival in cohort study of 310 patients (single-center study results and literature data

    Directory of Open Access Journals (Sweden)

    V. P. Pop

    2015-01-01

    Full Text Available Introduction. Chronic lymphoproliferative disease (CLPD are common hematologic malignancies, accompanied by highly variable clinical course, different prognosis and understudied survival as one of the main criteria for long-term treatment efficacy, especially outside of clinical trials.Materials and methods. Patients with CLPD (n = 310 treated in hematology center of Burdenko Main Military Clinical Hospital from June 2003 to September 2014 are included in the study. The diagnosis of specific nosology verified in accordance with national and international recommendations. Analysis of study outcomes was based on overall survival (OS using the Kaplan–Meier method.Results and discussion. Most patients (mainly with non-Hodgkin»s lymphoma (NHL – 75 %, or multiple myeloma (MM – 80.6 % had advanced disease (III–IV, and 20.3 % admitted to the hospital in poor general condition (ECOG somatic status – 3–4. A significant proportion of patients (38.3 % with NHL and Hodgkin lymphoma (HL had a large tumor masses. Median of OS in patients with CLPD was 81.1 months. 5-year survival of total patients from time of diagnosis was 62 %, 10-year survival rate – 37 %. Patients with MM have shortest median of OS – 39 months, while patients with chronic lymphocytic leukemia (CLL have the longest – 117.8 months. Median OS for NHL patients was 68.1 months, for HL patients – 99.3 months. When comparing survival for two time intervals (2003–2009 and 2009–2014, a tendency to increasethe survival rate for certain groups of patients with CLPD was revealed, that could be due to target therapy and new therapeutic approaches.Conclusion. New drug efficacy for certain diseases has led to renewed interest in the results of CLPD therapy. In our study, most CLPD patients have long-term OS, but the subsequent therapy lines influence on OS requires further study. These results will contribute to new developments in the organization and planning of

  14. Responses to panic induction procedures in subjects with multiple chemical sensitivity/idiopathic environmental intolerance: understanding the relationship with panic disorder.

    Science.gov (United States)

    Tarlo, Susan M; Poonai, Naveen; Binkley, Karen; Antony, Martin M; Swinson, Richard P

    2002-08-01

    Idiopathic environmental intolerance (IEI), also known as multiple chemical sensitivity, is a clinical description for a cluster of symptoms of unknown etiology that have been attributed by patients to multiple environmental exposures when other medical explanations have been excluded. Because allergy has not been clearly demonstrated and current toxicological paradigms for exposure-symptom relationships do not readily accommodate IEI, psychogenic theories have been the focus of a number of investigations. A significantly higher lifetime prevalence of major depression, mood disorders, anxiety disorders, and somatization disorder has been reported among patients with environmental illness compared with that in controls. Symptoms often include anxiety, lightheadedness, impaired mentation, poor coordination, breathlessness (without wheezing), tremor, and abdominal discomfort. Responses to intravenous sodium lactate challenge or single-breath inhalation of 35% carbon dioxide versus a similar breath inhalation of clean air have shown a greater frequency of panic responses in subjects with IEI than in control subjects, although such responses did not occur in all subjects. Preliminary genetic findings suggest an increased frequency of a common genotype with panic disorder patients. The panic responses in a significant proportion of IEI patients opens a therapeutic window of opportunity. Patients in whom panic responses may at least be a contributing factor to their symptoms might be responsive to intervention with psychotherapy to enable their desensitization or deconditioning of responses to odors and other triggers, and/or may be helped by anxiolytic medications, relaxation training, and counseling for stress management.

  15. Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders

    NARCIS (Netherlands)

    van Pelt, E. Danielle; Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.

    2014-01-01

    Background Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. Objective To evaluate the

  16. Subthreshold Conditions as Precursors for Full Syndrome Disorders: A 15-Year Longitudinal Study of Multiple Diagnostic Classes

    Science.gov (United States)

    Shankman, Stewart A.; Lewinsohn, Peter M.; Klein, Daniel N.; Small, Jason W.; Seeley, John R.; Altman, Sarah E.

    2009-01-01

    Background: There has been increasing interest in the distinction between subthreshold and full syndrome disorders and specifically whether subthreshold conditions escalate or predict the onset of full syndrome disorders over time. Most of these studies, however, examined whether a single subthreshold condition escalates into the full syndrome…

  17. Reliability and Diagnostic Efficiency of the Diagnostic Inventory for Disharmony (DID) in Youths with Pervasive Developmental Disorder and Multiple Complex Developmental Disorder

    Science.gov (United States)

    Xavier, Jean; Vannetzel, Leonard; Viaux, Sylvie; Leroy, Arthur; Plaza, Monique; Tordjman, Sylvie; Mille, Christian; Bursztejn, Claude; Cohen, David; Guile, Jean-Marc

    2011-01-01

    The Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) category is a psychopathological entity few have described and is poorly, and mainly negatively, defined by autism exclusion. In order to limit PDD-NOS heterogeneity, alternative clinical constructs have been developed. This study explored the reliability and the diagnostic…

  18. DIAGNOSING LYMPHOPROLIFERATIVE DISEASE VIRUS IN LIVE WILD TURKEYS (MELEAGRIS GALLOPAVO) USING WHOLE BLOOD.

    Science.gov (United States)

    Alger, Katrina; Bunting, Elizabeth; Schuler, Krysten; Jagne, Jarra; Whipps, Christopher M

    2015-12-01

    Lymphoproliferative disease virus (LPDV) is a retrovirus that infects wild and domestic turkeys ( Meleagris gallopavo ). The first cases of LPDV in the United States were diagnosed in 2009, and subsequent surveillance has revealed the virus to be widespread in wild turkey populations throughout the eastern half of the country. More research is needed to determine whether LPDV is having a negative effect on turkey populations, but progress has been impeded by the lack of a simple method for diagnosing the virus in living birds. Infected animals may appear asymptomatic, and diagnostics currently rely on tissue or bone marrow, which can be difficult to obtain. This study investigated the reliability of polymerase chain reaction (PCR) to detect LPDV in whole blood, compared with previous methods using buffy coat (concentrated white blood cells) and bone marrow. Paired samples of whole blood and buffy coat were collected from 137 live turkeys and paired samples of whole blood and bone marrow were collected from 32 turkeys postmortem. Compared with buffy coat, whole blood had 97% sensitivity and 100% specificity. When compared with bone marrow, whole blood had 100% sensitivity and 89% specificity. Both comparisons had a high degree of agreement using Cohen's kappa statistic. Based on these results, PCR of whole blood provides detection of LPDV in living birds that is on par with both buffy coat and bone marrow.

  19. Verotoxin targets lymphoma infiltrates of patients with post-transplant lymphoproliferative disease.

    Science.gov (United States)

    Arbus, G S; Grisaru, S; Segal, O; Dosch, M; Pop, M; Lala, P; Nutikka, A; Lingwood, C A

    2000-10-01

    Post-transplant lymphoproliferative disease (PTLD) is an invasive, EBV expressing B lymphoma and a major cause of morbidity and mortality following organ transplantation. Presently there is limited therapy available; rather the patient often loses the allograft or succumbs to the malignancy. CD77 (or globotriaosyl ceramide -Gb(3)) is a germinal center B cell marker [Gregory et al. Int J Cancer 1998;42:213-20; Gregory et al., J Immunol 1987;139:313-8; Mangeney et al. Eur J Immunol 1991;21:1131-40], expressed on most EBV infected B cells and is the receptor for the E. coli derived verotoxin (VT) [Lingwood CA. Advances in Lipid Research 1993;25:189-212]. We present the basis of a possible novel approach to PTLD therapy utilizing the specific targeting of VT to the infiltrating lymphoma cells. Biopsies of adenoid, kidney or liver tissue of four PTLD patients were stained with verotoxin to determine expression of CD77. VT is a potent inducer of necrosis/apoptosis of receptor positive cells. In each PTLD case, the infiltrating EBV positive B lymphoma cells were strongly and selectively stained with VT, identifying CD77 as a new marker for these cells. For such individuals, VT might provide the basis of an approach to control their malignancy.

  20. LYMPHO-PROLIFERATIVE RESPONSES TO VARIOUS FASCIOLA HEPATICA WORM'S ANTIGENS: AN IN VITRO STUDY.

    Science.gov (United States)

    Sharaf, Osama F; Amir, Elamir M; Hawash, Yousry A

    2016-04-01

    Fascioliasis is an important zoonotic disease with approximately 2-4 million people infected worldwide and a further 180 million at risk of infection. F. hepatica can survive within the bile ducts for many years through its ability to suppress the host immunity with Fasciola cathepsin L1 cysteine protease and Glutathione S transferase playing an important role. The aim of the present study is to investigate the in vitro lympho-proliferative responses of hepatic hilar lymphocytes (HLN) of infected sheep in response to different F. hepatica antigens. The suppressive effects of Fasciola excretory/secretory (ES) and tegument (TEG) and their fractions were also investigated. Our results showed that both ES and TEG had significant suppressive effects on lympho-proliferation, up to 74% and 92%, respectively. When these antigens were fractionated, fraction 3 (MW of >10000-30000) of both ES (64%) and TEG (59%) in addition to fraction 4 (MW of ≤ 10000) of TEG (38%) inherited the suppressive effects. Identification of the potential molecule(s) with such suppressive effects on lymphocytes in TEG fraction 4 could reveal vaccine candidates.

  1. Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation.

    Science.gov (United States)

    Magerus-Chatinet, Aude; Neven, Bénédicte; Stolzenberg, Marie-Claude; Daussy, Cécile; Arkwright, Peter D; Lanzarotti, Nina; Schaffner, Catherine; Cluet-Dennetiere, Sophie; Haerynck, Filomeen; Michel, Gérard; Bole-Feysot, Christine; Zarhrate, Mohammed; Radford-Weiss, Isabelle; Romana, Serge P; Picard, Capucine; Fischer, Alain; Rieux-Laucat, Frédéric

    2011-01-01

    Autoimmune diseases develop in approximately 5% of humans. They can arise when self-tolerance checkpoints of the immune system are bypassed as a consequence of inherited mutations of key genes involved in lymphocyte activation, survival, or death. For example, autoimmune lymphoproliferative syndrome (ALPS) results from defects in self-tolerance checkpoints as a consequence of mutations in the death receptor-encoding gene TNF receptor superfamily, member 6 (TNFRSF6; also known as FAS). However, some mutation carriers remain asymptomatic throughout life. We have now demonstrated in 7 ALPS patients that the disease develops as a consequence of an inherited TNFRSF6 heterozygous mutation combined with a somatic genetic event in the second TNFRSF6 allele. Analysis of the patients' CD4(-)CD8(-) (double negative) T cells--accumulation of which is a hallmark of ALPS--revealed that in these cells, 3 patients had somatic mutations in their second TNFRSF6 allele, while 4 patients had loss of heterozygosity by telomeric uniparental disomy of chromosome 10. This observation provides the molecular bases of a nonmalignant autoimmune disease development in humans and may shed light on the mechanism underlying the occurrence of other autoimmune diseases.

  2. An Appropriate Modulation of Lymphoproliferative Response and Cytokine Release as Possible Contributors to Longevity

    Science.gov (United States)

    Martínez de Toda, Irene; Vida, Carmen; De la Fuente, Mónica

    2017-01-01

    The decrease in the proliferative response of lymphocytes is one of the most evident among the age-related changes of the immune system. This has been linked to a higher risk of mortality in both humans and experimental animals. However, long-lived individuals, in spite of optimally maintaining most of the functions of the immune system, also seem to show an impaired proliferative response. Thus, it was hypothesized that these individuals may have distinct evolution times in this proliferation and a different modulatory capacity through their cytokine release profiles. An individualized longitudinal study was performed on female ICR-CD1 mice, starting at the adult age (40 weeks old), analyzing the proliferation of peritoneal leukocytes at different ages in both basal conditions and in the presence of the mitogen Concanavalin A, for 4, 24 and 48 h of culture. The cytokine secretions (IL-2, IL-17, IL-1β, IL-6, TNF-α and IL-10) in the same cultures were also studied. Long-lived mice show a high proliferative capacity after short incubation times and, despite experiencing a functional decline when they are old, are able to compensate this decrease with an appropriate modulation of the lymphoproliferative response and cytokine release. This could explain their elevated resistance to infections and high longevity. PMID:28737707

  3. PROBLEM OF FORMATION OF EMOTIONAL REACTION IN PRE-SCHOOL CHILDREN WITH MULTIPLE DEVELOPMENTAL DISORDERS IN SUBJECT-COMMUNICATIVE ACTIVITY IN THE CONDITIONS OF KINDERGARTEN

    Directory of Open Access Journals (Sweden)

    Ольга Валентиновна Шохова

    2013-11-01

    Full Text Available The article is devoted to the problem of emotional response in children with developmental disorders in subject-communicative activity . The characteristic of the particularities of emotional reaction in children with divelopmental disorders is given. The author proves that it is necessary to develop emotional response as the base for further social adaptation of children with multiple disorders in development; mechanisms of formation of emotional reaction in communicative activity are described: contents, methods used for multiple diorders. Experimental data has proved the effectiveness of pedagogical thechnology on forming of emotional reaction in subject-communicative activity. Corrective and development work used in this technology is based on principles of integrity, complexness; the interralated series of thematical studies is organized intended for develoment of motor, sensor, communicative and emotional sphere in different activities of children. All this facilitate gradual interiorization of emotional reactions, their automatization in communicative activity.DOI: http://dx.doi.org/10.12731/2218-7405-2013-10-7

  4. Collaborative Care for patients with severe borderline and NOS personality disorders: A comparative multiple case study on processes and outcomes

    NARCIS (Netherlands)

    dr Barbara Stringer; Ad Kerkhof; Aartjan Beekman; prof Berno van Meijel

    2011-01-01

    Background: Structured psychotherapy is recommended as the preferred treatment of personality disorders. A substantial group of patients, however, has no access to these therapies or does not benefit. For those patients who have no (longer) access to psychotherapy a Collaborative Care Program (CCP)

  5. Behavioral interventions in Attention-Deficit/ Hyperactivity Disorder: a meta-analysis of randomized controlled trials across multiple outcome domains

    NARCIS (Netherlands)

    D. Daley; S. van der Oord; M. Ferrin; M. Danckaerts; M. Doepfner; S. Cortese; E.J.S. Sonuga-Barke

    2014-01-01

    OBJECTIVE: Behavioral interventions are recommended as attention-deficit/hyperactivity disorder (ADHD) treatments. However, a recent meta-analysis found no effects on core ADHD symptoms when raters were probably blind to treatment allocation. The present analysis is extended to a broader range of ch

  6. HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2.

    Science.gov (United States)

    De Re, Valli; De Zorzi, Mariangela; Caggiari, Laura; Lauletta, Gianfranco; Tornesello, Maria Lina; Fognani, Elisa; Miorin, Marta; Racanelli, Vito; Quartuccio, Luca; Gragnani, Laura; Russi, Sabino; Pavone, Fabio; Ghersetti, Michela; Costa, Elena Garlatti; Casarin, Pietro; Bomben, Riccardo; Mazzaro, Cesare; Basaglia, Giancarlo; Berretta, Massimiliano; Vaccher, Emanuela; Izzo, Francesco; Buonaguro, Franco Maria; De Vita, Salvatore; Zignego, Anna Linda; De Paoli, Paolo; Dolcetti, Riccardo

    2016-06-21

    To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression.

  7. Single versus multiple impulse control disorders in Parkinson's disease: an ¹¹C-raclopride positron emission tomography study of reward cue-evoked striatal dopamine release.

    Science.gov (United States)

    Wu, Kit; Politis, Marios; O'Sullivan, Sean S; Lawrence, Andrew D; Warsi, Sarah; Bose, Subrata; Lees, Andrew J; Piccini, Paola

    2015-06-01

    Impulse control disorders (ICDs) are reported in Parkinson's disease (PD) in association with dopaminergic treatment. Approximately 25 % of patients with ICDs have multiple co-occurring ICDs (i.e. more than one diagnosed ICD). The extent to which dopaminergic neurotransmission in PD patients with multiple ICDs differs from those with only one diagnosed ICD is unknown. The aims of this study are: (1) to investigate dopamine neurotransmission in PD patients diagnosed with multiple ICDs, single ICDs and non-ICD controls in response to reward-related visual cues using positron emission tomography with (11)C-raclopride. (2) to compare clinical features of the above three groups. PD individuals with mulitple ICDs (n = 10), single ICD (n = 7) and no ICDs (n = 9) were recruited and underwent two positron emission tomography (PET) scans with (11)C-raclopride: one where they viewed neutral visual cues and the other where they viewed a range of visual cues related to different rewards. Individuals with both multiple ICDs and single ICDs showed significantly greater ventral striatal dopamine release compared to non-ICD PD individuals in response to reward cues, but the two ICD groups did not differ from each other in the extent of dopamine release. Subjects with multiple ICDs were, however, significantly more depressed, and had higher levels of impulsive sensation-seeking compared to subjects with single ICDs and without ICDs. This is the first study to compare dopamine neurotransmission using PET neuroimaging in PD subjects with multiple vs. single ICDs. Our results suggest that striatal dopamine neurotransmission is not directly related to the co-occurrence of ICDs in PD, potentially implicating non-dopaminergic mechanisms linked to depression; and suggest that physicians should be vigilant in managing depression in PD patients with ICDs.

  8. Renal complications in multiple myeloma and related disorders: Survivorship care plan of the IMF Nurse Leadership Board

    Science.gov (United States)

    Faiman, Beth; Tariman, Joseph D.; Mangan, Patricia A.; Spong, Jacy

    2012-01-01

    Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease, and which, if not reversed, will adversely effect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis due to light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma may also result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore identification of patients at risk for kidney damage is essential. The International Myeloma Foundation’s Nurse Leadership Board have developed these practice recommendations for screening for renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD and dialysis, and reducing and managing renal complications in patients with multiple myeloma. PMID:21816711

  9. Renal complications in multiple myeloma and related disorders: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

    Science.gov (United States)

    Faiman, Beth M; Mangan, Patricia; Spong, Jacy; Tariman, Joseph D

    2011-08-01

    Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease and, if not reversed, will adversely affect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis because of light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma also may result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore, identification of patients at risk for kidney damage is essential. The International Myeloma Foundation's Nurse Leadership Board has developed practice recommendations for screening renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD, and enacting dialysis to reduce and manage renal complications in patients with multiple myeloma.

  10. Therapeutic Horseback Riding Outcomes of Parent-Identified Goals for Children with Autism Spectrum Disorder: An ABA' Multiple Case Design Examining Dosing and Generalization to the Home and Community

    Science.gov (United States)

    Holm, Margo B.; Baird, Joanne M.; Kim, Young Joo; Rajora, Kuwar B.; D'Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy

    2014-01-01

    We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6-8 years…

  11. Multiple lattice instabilities resolved by magnetic-field and disorder sensitivities in MgV2O4

    Science.gov (United States)

    Watanabe, Tadataka; Ishikawa, Takashi; Hara, Shigeo; Islam, A. T. M. Nazmul; Wheeler, Elisa M.; Lake, Bella

    2014-09-01

    Ultrasound velocity measurements of the orbitally degenerate frustrated spinel MgV2O4 are performed in a high-purity single crystal which exhibits successive structural and antiferromagnetic phase transitions, and in the disorder-introduced single crystal which exhibits spin-glass-like behavior. The measurements reveal that two types of unusual temperature dependence of the elastic moduli coexist in the cubic paramagnetic phase, which are resolved by magnetic-field and disorder sensitivities: huge Curie-type softening with decreasing temperature (convex temperature dependence), and concave temperature dependence with a characteristic minimum. These elastic anomalies suggest the coupling of the lattice to coexisting orbital fluctuations and spin-cluster excitations.

  12. Peptide Regulation of Cofilin Activity in the CNS: A Novel Therapeutic Approach for Treatment of Multiple Neurological Disorders.

    Science.gov (United States)

    Shaw, Alisa E; Bamburg, James R

    2017-02-19

    Cofilin is a ubiquitous protein which cooperates with many other actin-binding proteins in regulating actin dynamics. Cofilin has essential functions in nervous system development including neuritogenesis, neurite elongation, growth cone pathfinding, dendritic spine formation, and the regulation of neurotransmission and spine function, components of synaptic plasticity essential for learning and memory. Cofilin's phosphoregulation is a downstream target of many transmembrane signaling processes, and its misregulation in neurons has been linked in rodent models to many different neurodegenerative and neurological disorders including Alzheimer disease (AD), aggression due to neonatal isolation, autism, manic/bipolar disorder, and sleep deprivation. Cognitive and behavioral deficits of these rodent models have been largely abrogated by modulation of cofilin activity using viral-mediated, genetic, and/or small molecule or peptide therapeutic approaches. Neuropathic pain in rats from sciatic nerve compression has also been reduced by modulating the cofilin pathway within neurons of the dorsal root ganglia. Neuroinflammation, which occurs following cerebral ischemia/reperfusion, but which also accompanies many other neurodegenerative syndromes, is markedly reduced by peptides targeting specific chemokine receptors, which also modulate cofilin activity. Thus, peptide therapeutics offer potential for cost-effective treatment of a wide variety of neurological disorders. Here we discuss some recent results from rodent models using therapeutic peptides with a surprising ability to cross the rodent blood brain barrier and alter cofilin activity in brain. We also offer suggestions as to how neuronal-specific cofilin regulation might be achieved.

  13. A Fashi Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation

    Science.gov (United States)

    Menezes, Soraya Maria; Leal, Fabio E.; Dierckx, Tim; Khouri, Ricardo; Decanine, Daniele; Silva-Santos, Gilvaneia; Schnitman, Saul V.; Kruschewsky, Ramon; López, Giovanni; Alvarez, Carolina; Talledo, Michael; Gotuzzo, Eduardo; Nixon, Douglas F.; Vercauteren, Jurgen; Brassat, David; Liblau, Roland; Vandamme, Anne Mieke; Galvão-Castro, Bernardo; Van Weyenbergh, Johan

    2017-01-01

    Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fashi T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation, and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC), and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fashi cells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation upon in vitro culture, but not to proviral load. This Fashi phenotype is HAM/TSP-specific, since both ex vivo and in vitro Fas expression was increased as compared to multiple sclerosis (MS), another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signaling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e., blocking vs. triggering Fas receptor in vitro with antagonist and agonist-, anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis, indicating

  14. "Nothing like Pretend": Difference, Disorder, and Dystopia in the Multiple World Spaces of Philip Pullman's "His Dark Materials"

    Science.gov (United States)

    Cantrell, Sarah K.

    2010-01-01

    This article examines the multiple worlds in Philip Pullman's "His Dark Materials" trilogy in light Pierre Bourdieu's "space of possibles" and the combination of chance and choice that impact Lyra and Will's decisions. Rather than viewing chance or destiny as disempowering, this article considers how the protagonists' choices also encourage…

  15. Genome-wide scan in Portuguese Island families implicates multiple loci in bipolar disorder: fine mapping adds support on chromosomes 6 and 11.

    Science.gov (United States)

    Pato, Carlos N; Pato, M T; Kirby, A; Petryshen, T L; Medeiros, H; Carvalho, C; Macedo, A; Dourado, A; Coelho, I; Valente, J; Soares, M J; Ferreira, C P; Lei, M; Verner, A; Hudson, T J; Morley, C P; Kennedy, J L; Azevedo, M H; Daly, M J; Sklar, P

    2004-05-15

    As part of an extensive study in the Portuguese Island population of families with multiple patients suffering from bipolar disorder and schizophrenia, we performed an initial genome-wide scan of 16 extended families with bipolar disorder that identified three regions on chromosomes 2, 11, and 19 with genome-wide suggestive linkage and several other regions, including chromosome 6q, also approached suggestive levels of significance. Dick et al. [2003: Am J Hum Genet 73:107-114] recently reported in a study of 250 families with bipolar disorder a maxLOD score of 3.61 near marker D6S1021 on chromosome 6q. This study replicates this finding having detected a peak NPL = 2.02 (P = 0.025) with the same marker D6S1021(104.7 Mb). Higher-density mapping provided additional support for loci on chromosome 6 including marker D6S1021 with an NPL = 2.59 (P = 0.0068) and peaking at marker D6S1639 (125 Mb) with an NPL = 3.06 (P = 0.0019). A similar pattern was detected with higher-density mapping of chromosome 11 with an NPL = 3.15 (P = 0.0014) at marker D11S1883 (63.1 Mb). Simulations at the density of our fine mapping data indicate that less than 1 scan out of 10 would find two such scores genome-wide in the same scan by chance. Our findings provide additional support for a susceptibility locus for bipolar disorder on 6q, as well as, suggesting the importance of denser scans. Published 2004 Wiley-Liss, Inc.

  16. Epstein-Barr Virus-Negative Post-Transplant Lymphoproliferative Diseases: Three Distinct Cases from a Single Center

    Directory of Open Access Journals (Sweden)

    Şule Mine Bakanay

    2014-03-01

    Full Text Available Three cases of Epstein-Barr virus (EBV-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Manbok, E-mail: manbok66@dankook.ac.kr [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Rahman, Masmudur M. [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Cogle, Christopher R. [Department of Hematology/Oncology, University of Florida, Gainesville, FL 32610 (United States); McFadden, Grant [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States)

    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. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.

  18. Epstein-barr virus-negative post-transplant lymphoproliferative diseases: three distinct cases from a single center.

    Science.gov (United States)

    Bakanay, Sule Mine; Kaygusuz, Gülşah; Topçuoğlu, Pervin; Sengül, Sule; Tunçalı, Timur; Keven, Kenan; Kuzu, Işınsu; Uysal, Akın; Arat, Mutlu

    2014-03-01

    Three cases of Epstein-Barr virus (EBV)-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

  19. Non-malignant T-cells lacking multiple pan-T markers can be found in lymph nodes.

    Science.gov (United States)

    Wang, Wei; Gao, Li; Gong, Ming; Tang, Yin; Li, Yan; Zhang, Wen-Tao; Huang, Fan-Zhou; Zhang, Chun-Xia; Chen, Yan-Rong; Gao, Ya-Yue; Li, Zhen-Ling; Ma, Yi-Gai

    2018-01-01

    In order to observe and ascertain the properties of a sub-group of T cells in the lymph node (LN) from seven patients who did not suffer from T cell lymphoproliferative disorders (T-LPDs), the expression levels of several pan-T markers were evaluated by multiparameter flow cytometry (FC) and the clonality of these T-cells was evaluated by both FC analysis and PCR assessment. It turned out that multiple pan-T-cell markers such as CD2, CD5 and CD7 were found to be lost in these T cells. The majority of them were positive for TCRαβ, only a minority of them being positive for TCRγδ. A subset of these T-cells were positive for CD4 or CD8 or dual-negative for CD4 and CD8. Oligoclonality was detected in one case by FC, while clonal TCR rearrangement was detected in three cases. Absence of multiple pan-T-cell markers could be found in benign T cells in LNs.

  20. Annual Research Review: The neurobehavioral development of multiple memory systems: implications for childhood and adolescent psychiatric disorders

    OpenAIRE

    Goodman, Jarid; Marsh, Rachel; Peterson, Bradley S.; Packard, Mark G.

    2013-01-01

    Extensive evidence indicates that mammalian memory is organized into multiple brains systems, including a “cognitive” memory system that depends upon the hippocampus and a stimulus-response “habit” memory system that depends upon the dorsolateral striatum. Dorsal striatal-dependent habit memory may in part influence the development and expression of some human psychopathologies, particularly those characterized by strong habit-like behavioral features. The present review considers this hypoth...

  1. Intricate Crystal Structure of Dihydrolipoamide Dehydrogenase (E3) with its Binding Protein: Multiple Copies, Dynamic and Static Disorders

    Science.gov (United States)

    Makal, A.; Hong, Y. S.; Potter, R.; Vettaikkorumakankauv, A. K.; Korotchkina, L. G.; Patel, M. S.; Ciszak, E.

    2004-01-01

    Human E3 and binding protein E3BP are two components of the pyruvate dehydrogenase complex. Crystallization of E3 with 221-amino acid fragment of E3BP (E3BPdd) led to crystals that diffracted to a resolution of 2.6 Angstroms. Structure determination involved molecular replacement using a dimer of E3 homolog as a search model and de novo building of the E3BPdd peptide. Solution was achieved by inclusion of one E3 dimer at a time, followed by refinement until five E3 dimers were located. This complete content of E3 provided electron density maps suitable for tracing nine peptide chains of E3BPdd, eight of them being identified with partial occupancies. Final content of the asymmetric unit consists of five E3 dimers, each binding one E3BPdd molecule. In four of these molecular complexes, E3BPdd is in static disorder resulting in E3BPdd binding to either one or the other monomer of the E3 dimer. However, E3BPdd of the fifth E3 dimer forms specific contacts that lock it at one monomer. In addition to this static disorder, E3BPdd reveals high mobility in the limited space of the crystal lattice. Support from NIH and NASA.

  2. Hepatosplenic gamma-delta T-cell lymphoma as a late-onset posttransplant lymphoproliferative disorder in renal transplant recipients.

    Science.gov (United States)

    Wu, H; Wasik, M A; Przybylski, G; Finan, J; Haynes, B; Moore, H; Leonard, D G; Montone, K T; Naji, A; Nowell, P C; Kamoun, M; Tomaszewski, J E; Salhany, K E

    2000-04-01

    We report 2 cases of renal transplant recipients in whom hepatosplenic gamma-delta T-cell lymphoma (gamma-delta HSTCL) developed 5 and 10 years after transplantation. Both patients had marked hepatosplenomegaly, B symptoms (weight loss, fever, and night sweats), and abnormal peripheral blood findings, including anemia in both, thrombocytopenia and leukoerythroblastic changes in 1, and leukocytosis in the other. Markedly atypical lymphoid infiltrate of intermediate to large cells was observed in the spleen, liver, and bone marrow. The malignant cells showed typical immunophenotype of gamma-delta T cells (CD2+, CD3+, CD4-, CD8-, CD7+, gamma-delta T-cell receptor-positive, and alpha-beta T-cell receptor-negative) with clonal T-cell receptor gene rearrangement and were of the V-delta-1 subset. In addition, the cells contained a cytolytic granule-associated protein, TIA-1, and Fas ligand, indicating cytotoxic T-cell differentiation. The malignant T cells in both cases were of host tissue origin. Both cases were negative for Epstein-Barr virus genome using Southern blot analysis. The patients did not respond to reduction of immunosuppression. Despite initial response to chemotherapy, both patients died within 6 months of diagnosis. Our findings indicate that gamma-delta HSTCL can occur as a late complication in transplant recipients.

  3. Immune ThrombocytoPenia (ITP) secondary to Chronic Lymphoproliferative Disorders (LPDs) | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available ome complicanza della malattia linfoproliferativa (linfoma o leucemia linfatica c...do la classificazione WHO del 2008: piccolo linfoma linfocitico/leucemia linfatica cronica, linfoma follicol...are, linfoma della zona marginale, linfoma a cellule del mantello, linfoma linfoplasmacellulare, leucemia a

  4. Fatal EBV-related post-transplant lymphoproliferative disorder (LPD) after matched related donor nonmyeloablative peripheral blood progenitor cell transplant.

    Science.gov (United States)

    Zamkoff, K W; Bergman, S; Beaty, M W; Buss, D H; Pettenati, M J; Hurd, D D

    2003-02-01

    A 39-year-old male underwent a nonmyeloablative stem cell transplant (NMAPBPCT) from his HLA-matched sister for recurrent anaplastic large cell lymphoma in CR-2, receiving fludarabine, cyclophosphamide, and rabbit antithymocyte globulin for the preparative therapy. The patient was readmitted on day+33 for persistent culture-negative fevers. He rapidly developed marked elevations of alkaline phosphatase and bilirubin. Liver biopsy showed a periportal infiltrate of large immunoblastic appearing cells. The tumor cells did not stain for CD3/CD20/CD30 and alk protein, but did stain for CD79a/LCA and CD43. In situ hybridization for Epstein-Barr virus (EBV) RNA (EBER 1) was strongly positive in the periportal infiltrating lymphocytes. Fluorescence in situ hybridization (FISH) studies revealed female (XX) cells in the tumor cells and male (XY) in the surrounding hepatic parenchymal cells. The patient developed severe lactic acidosis, oliguric renal failure and expired on day+44. Both donor and patient had positive IgG serologies for EBV VCA and EBNA pretransplant. The donor also had a positive IgM titer for EBV VCA in the pretransplant specimen. The LPD may have been related to the intense immunosuppression of the preparative therapy and the presence of recent EBV infection in the donor.

  5. Multiparametric analyses of human PBMCs loaded ex vivo with a candidate idiotype vaccine for HCV-related lymphoproliferative disorders.

    Directory of Open Access Journals (Sweden)

    Annacarmen Petrizzo

    Full Text Available Hepatitis C virus (HCV has been identified as one of the major risk factors for type II mixed cryoglobulinemia (MC, during the clinical evolution of chronic hepatitis, which may lead to development of B cell non-Hodgkin's lymphoma (NHL. We have previously shown that the candidate idiotype vaccine, based on the IGKV3-20 light chain protein, is able to induce activation and maturation of circulating antigen presenting cells (APCs in both HCV-positive and HCV-negative healthy control subjects, with production of Th2-type cytokines. Here, the effect of the recombinant IGKV3-20 protein on human peripheral blood mononuclear cells (PBMCs from HCV-positive subjects, with known blood levels of cryoglobulins, is shown via gene expression profiling analysis combined to multiparameter flow cytometry and multiplex analyses of cytokines.

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

    OpenAIRE

    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.; Mark R Pittelkow; Witzig, Thomas E.; Ansell, Stephen M.

    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 su...

  7. Cold antibody autoimmune hemolytic anemia and lymphoproliferative disorders: a retrospective study of 20 patients including clinical, hematological, and molecular findings.

    Science.gov (United States)

    Arthold, Cathrin; Skrabs, Cathrin; Mitterbauer-Hohendanner, Gerlinde; Thalhammer, Renate; Simonitsch-Klupp, Ingrid; Panzer, Simon; Valent, Peter; Lechner, Klaus; Jäger, Ulrich; Sillaber, Christian

    2014-06-01

    A total of 20 patients with cold antibody hemolytic anemia were evaluated in a retrospective study of them, 15 had a monoclonal gammopathy of unknown significance (MGUS): 14 with MGUS of immunoglobulin M (IgM) subtype and 1 with immunoglobulin G subtype. One patient had smoldering Waldenström's macroglobulinemia, but four patients had no monoclonal protein and no evidence of lymphoma. However, in three of these patients, we were able to demonstrate a (mono-)clonal rearrangement of their immunoglobulin heavy and/or light chains. Of the 20 patients, 5 had IgHV34 nucleotide sequence indicating that the antibody was directed against the "I" antigen. Two patients exhibited a progressive increase of IgM over time, however without increasing hemolytic activity. Moreover, in two patients with long-term follow-up, we were able to correlate recurrent hemolytic activity with low environmental temperatures. Among four patients treated with rituximab, all four responded to treatment. However, treatment effect was only transient in all of them.

  8. Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: A surrogate marker for NK-cell clonality

    NARCIS (Netherlands)

    P. Bárcena (Paloma); M. Jara-Acevedo (M.); M.D. Tabernero; A. López (Antonio); M.-L. Sánchez (M.); A.C. García-Montero (Andrés); N. Muñoz-García (Noemí); M.B. Vidriales (M.); A. Paiva (Artur); Q. Lecrevisse (Quentin); M. Lima (Margarida); A.W. Langerak (Ton); S. Böttcher (Stephan); J.J.M. van Dongen (Jacques); A. Orfao (Alberto); J. Almeida (Julia)

    2015-01-01

    textabstractCurrently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for

  9. Multiple System Atrophy (MSA)

    Science.gov (United States)

    Diseases and Conditions Multiple system atrophy (MSA) By Mayo Clinic Staff Multiple system atrophy (MSA) is a rare neurological disorder that impairs your body's involuntary (autonomic) functions, including blood ...

  10. Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients

    NARCIS (Netherlands)

    Stevens, SJC; Verschuuren, EAM; Pronk, [No Value; van der Bij, W; Harmsen, MC; The, TH; Meijer, CJLM; van den Brule, AJC; Middeldorp, JM

    2001-01-01

    Posttransplant lymphoproliferative disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)-associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function, The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectiv

  11. Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease

    NARCIS (Netherlands)

    Verschuuren, E; van der Bij, W; de Boer, W; Timens, W; Middeldorp, J; The, TH

    2003-01-01

    The Epstein-Barr virus (EBV)-specific antibody response was studied in lung transplant patients to assess their value in the diagnosis and prognosis of post-transplant lymphoproliferative disease. Recently developed synthetic peptides representing Epstein-Barr nuclear antigen-1 (EBNA-1), diffuse ear

  12. Soluble CD40 ligand contributes to blood-brain barrier breakdown and central nervous system inflammation in multiple sclerosis and neuromyelitis optica spectrum disorder.

    Science.gov (United States)

    Masuda, Hiroki; Mori, Masahiro; Uchida, Tomohiko; Uzawa, Akiyuki; Ohtani, Ryohei; Kuwabara, Satoshi

    2017-04-15

    Soluble CD40 ligand (sCD40L) is reported to disrupt the blood-brain barrier (BBB). Cerebrospinal fluid (CSF) and serum sCD40L levels were measured in 29 multiple sclerosis (MS), 29 neuromyelitis optica spectrum disorder (NMOSD), and 27 disease control (DC) patients. In MS, serum sCD40L levels were higher than in DCs and positively correlated with the CSF/serum albumin ratio (Qalb). In NMOSD, CSF sCD40L levels were significantly increased compared to DCs, and were correlated to Qalb, CSF cell counts, protein concentrations, and interleukin-6 levels. sCD40L could be involved in BBB disruption in MS, whereas it may contribute to CNS inflammation in NMOSD. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Treating Post-traumatic Stress Disorder in patients with Multiple Sclerosis: a randomized controlled trial comparing the efficacy of Eye Movement Desensitization and Reprocessing and Relaxation Therapy.

    Directory of Open Access Journals (Sweden)

    Sara eCarletto

    2016-04-01

    Full Text Available Objective: Multiple Sclerosis (MS is a demyelinating autoimmune disease that imposes a significant emotional burden with heavy psychosocial consequences. Several studies have investigated the association between MS and mental disorders such as depression and anxiety, and recently researchers have focused also on Post-traumatic Stress Disorder (PTSD. This is the first study that investigates the usefulness of proposing a treatment for PTSD to patients with MS. Methods: A randomized controlled trial with patients with MS diagnosed with PTSD comparing Eye Movement Desensitization and Reprocessing (EMDR; n = 20 and Relaxation Therapy (RT; n = 22. The primary outcome measure was the proportion of participants that no longer meet PTSD diagnosis as measured with Clinician Administered PTSD Scale six-months after the treatment.Results: The majority of patients were able to overcome their PTSD diagnosis after only 10 therapy sessions. EMDR treatment appears to be more effective than RT in reducing the proportion of patients with MS suffering from PTSD. Both treatments are effective in reducing PTSD severity, anxiety symptoms and to improve Quality of Life (QoL. Conclusions: Although our results can only be considered preliminary, this study suggests that it is essential that PTSD symptoms are detected and that brief and cost-effective interventions to reduce PTSD and associated psychological symptoms are offered to patients, in order to help them to reduce the psychological burden associated with their neurological condition.Trail registration: NCT01743664, https://clinicaltrials.gov/ct2/show/NCT01743664

  14. InMS: Chronic insomnia disorder in multiple sclerosis - a Portuguese multicentre study on prevalence, subtypes, associated factors and impact on quality of life.

    Science.gov (United States)

    Viana, Pedro; Rodrigues, Elisabete; Fernandes, Carina; Matas, Andreia; Barreto, Rui; Mendonça, Marcelo; Peralta, Rita; Geraldes, Ruth

    2015-09-01

    Sleep may be disrupted in Multiple Sclerosis (MS), but the prevalence of chronic insomnia disorder (CID) using standard diagnostic criteria is unknown. To determine the prevalence of CID in an MS population, the frequency of CID subtypes, associated factors and impact on quality of life (QoL). Multicentre, hospital-based cross-sectional study. An adapted version of the Brief Insomnia Questionnaire was applied to a consecutively recruited MS population. The influence of demographic, MS-related features, fatigue, medical and psychiatric comorbidities, nocturnal symptoms, other sleep disorders, dysfunctional beliefs about sleep in CID was evaluated. The relation between CID and QoL was analysed. Of 206 MS patients, 22.3% fulfilled criteria for CID, with initial insomnia in 11.7%, maintenance insomnia in 11.2% and terminal insomnia in 10.2% of patients. CID was more frequent in female patients, those with nocturnal symptoms, medical comorbidities, higher levels of anxiety, depression and fatigue. Multivariable analysis identified female sex, medical comorbidities, anxiety and fatigue as independent factors for CID. CID patients had a significantly lower self-reported QoL. CID is prevalent in MS patients and associated with psychiatric and medical comorbidities, as well as fatigue. It has a negative impact on QoL. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Affective disorders and Health-Related Quality of Life (HRQoL) in adolescents and young adults with Multiple Sclerosis (MS): the moderating role of resilience.

    Science.gov (United States)

    Rainone, Nunzia; Chiodi, Alessandro; Lanzillo, Roberta; Magri, Valeria; Napolitano, Anna; Morra, Vincenzo Brescia; Valerio, Paolo; Freda, Maria Francesca

    2017-03-01

    To investigate the moderating role of resilience in the relationship between affective disorders and Health-Related Quality of Life (HRQoL) for adolescents and young adults with multiple sclerosis (MS). A quantitative methodology was adopted. Fifty-three adolescents and young adults were interviewed to assess resilience as a personality trait (Ego-Resiliency Scale) and resilience as an interactive competence (CYRM-28), Health-Related Quality of Life (PedsQL 4.0), depression and anxiety (BDI-II and STAI-Y). Affective disorders, both depression (β = -.38, p resilience competencies using Individual (β = .22, p resilience competence using individual resources on the relationship between the Depression Cognitive Factor and Emotional Functioning. Data show that in step 2 of the regression analysis, we obtained a variation of β = -.45 (p resilience was significant regarding the increase in R(2) (p Resilience competence using individual resources moderates the relationship between the Depression Cognitive Factor and Emotional Functioning in adolescents with MS. Our study suggests that to improve well-being for adolescents with MS resilience could play a key role.

  16. Are there any associations between single and/or multiple social roles and self-rated physical health, psychiatric disorder and long-term sickness absence in women?

    Directory of Open Access Journals (Sweden)

    Carin Staland Nyman

    2012-03-01

    Full Text Available

    Abstract:
    Background: the relationship between single and/or multiple social roles that women hold (occupa- tional, partner, and parent and health and sickness absence is an important public health issue. Few studies on the social roles held by women have been performed in the Swedish context of gender equality. The aim of this study was to analyse associations between occupational, partner and parent roles (and combinations of these roles and their relation to self-rated physical health, psychiatric disorders and long-term sickness absence in a population based sample of women in Sweden.
    Methods: women born in 1935, 1945, 1955, 1965, 1970 or 1975 (n=600 were interviewed at baseline and five years later. cross-sectional data were analysed with multivariate logistic regression analysis adjusted for age, socio-economic position, alcohol dependence and abuse.
    Results: an occupational role was associated with lower odds for poor self-rated physical health, 0.28 (0.10-0.82, and sickness absence, 0.25 (0.10-0.86. a partner role was associated with lower odds for psy- chiatric disorder, 0.58 (0.35-0.98 while a parental role (children < 14 years was associated with higher odds for sickness absence, 4.17 (1.86-9.38. The combination of holding an occupational and partner role was associated with lower odds for health outcomes compared with having three roles. Conclusion: holding an occupational and partner role was related to lower odds for poor self-rated physical health, psychiatric disorder and long-term sickness absence, while having a parental role was adversely related to sickness absence. results are important in the light of discussions on reconciliation of work and family, and are of interest in countries with high or increasing female labour force participation.

  17. Mosaicism for genome-wide paternal uniparental disomy with features of multiple imprinting disorders: diagnostic and management issues.

    Science.gov (United States)

    Inbar-Feigenberg, Michal; Choufani, Sanaa; Cytrynbaum, Cheryl; Chen, Yi-An; Steele, Leslie; Shuman, Cheryl; Ray, Peter N; Weksberg, Rosanna

    2013-01-01

    Mosaicism for genome-wide paternal uniparental disomy (UPD) has been reported in only seven live born individuals to date. Clinical presentation includes manifestations of multiple paternal UPD syndromes with high variability, likely due to the variable levels of mosaicism in different somatic tissues. We report an eighth case in a female patient with mosaicism for genome-wide paternal UPD which highlights the complex clinical presentation. Our patient had features of Beckwith-Wiedemann syndrome (BWS), Angelman syndrome, and congenital hyperinsulinism. The clinical findings included prematurity, organomegaly, hemihyperplasia, developmental delay, benign tumors, and cystic lesions. The diagnosis in our patient was established utilizing microarray-based genome-wide DNA methylation analysis performed on leukocyte DNA. Targeted multiplex ligation-dependent probe amplification (MLPA) analysis of chromosome regions 11p15 and 15q13 confirmed mosaicism for paternal UPD at these genomic regions. This case represents the first report of microarray-based genome-wide DNA methylation analysis in the diagnosis of genome-wide paternal UPD. The application of microarray-based genome-wide DNA methylation analysis on selected individuals with complex clinical presentations could be a valuable diagnostic tool to improve the detection rate of mosaic genome-wide paternal UPD. This approach, which screens many loci simultaneously, is more cost-effective and less labor-intensive than performing multiple targeted DNA methylation-based assays. Identification of individuals with mosaicism for genome-wide paternal UPD is an important goal as it confers a low recurrence risk for the family and identifies individuals who require surveillance due to increased tumor risk.

  18. Anchoring Intrinsically Disordered Proteins to Multiple Targets: Lessons from N-Terminus of the p53 Protein

    Directory of Open Access Journals (Sweden)

    Yongqi Huang

    2011-02-01

    Full Text Available Anchor residues, which are deeply buried upon binding, play an important role in protein–protein interactions by providing recognition specificity and facilitating the binding kinetics. Up to now, studies on anchor residues have been focused mainly on ordered proteins. In this study, we investigated anchor residues in intrinsically disordered proteins (IDPs which are flexible in the free state. We identified the anchor residues of the N-terminus of the p53 protein (Glu17–Asn29, abbreviated as p53N which are involved in binding with two different targets (MDM2 and Taz2, and analyzed their side chain conformations in the unbound states. The anchor residues in the unbound p53N were found to frequently sample conformations similar to those observed in the bound complexes (i.e., Phe19, Trp23, and Leu26 in the p53N-MDM2 complex, and Leu22 in the p53N-Taz2 complex. We argue that the bound-like conformations of the anchor residues in the unbound state are important for controlling the specific interactions between IDPs and their targets. Further, we propose a mechanism to account for the binding promiscuity of IDPs in terms of anchor residues and molecular recognition features (MoRFs.

  19. Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Teuscher NS

    2015-05-01

    Full Text Available Nathan S Teuscher,1 Akwete Adjei,2 Robert L Findling,3,4 Laurence L Greenhill,5 Robert J Kupper,2 Sharon Wigal6 1PK/PD Associates, Trophy Club, TX, 2Rhodes Pharmaceuticals L.P., Coventry, RI, 3Department of Psychiatric Services and Research, Kennedy Krieger Institute, Baltimore, MD, 4Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, 5Department of Psychiatry, Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY, 6AVIDA Inc., Newport Beach, CA, USA Abstract: A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR has been evaluated in pharmacokinetic studies in healthy adults and in Phase III efficacy/safety studies in children and adolescents with attention deficit hyperactivity disorder (ADHD. Using available data in healthy adults, a two-input, one-compartment, first-order elimination population pharmacokinetic model was developed using nonlinear mixed-effect modeling. The model was then extended to pediatric subjects, and was found to adequately describe plasma concentration–time data for this population. A pharmacokinetic/pharmacodynamic model was also developed using change from baseline in the ADHD Rating Scale (ADHD-RS-IV total scores from a pediatric Phase III trial and simulated plasma concentration–time data. During simulations for each MPH-MLR dose level (10–80 mg, increased body weight resulted in decreased maximum concentration. Additionally, as maximum concentration increased, ADHD-RS-IV total score improved (decreased. Knowledge of the relationship between dose, body weight, and clinical response following the administration of MPH-MLR in children and adolescents may be useful for clinicians selecting initial dosing of MPH-MLR. Additional study is needed to confirm these results. Keywords: population pharmacokinetics, Aptensio XR™, MPH-MLR, methylphenidate

  20. Comparison Study of Polysomnographic Features in Multiple System Atrophy-cerebellar Types Combined with and without Rapid Eye Movement Sleep Behavior Disorder

    Institute of Scientific and Technical Information of China (English)

    Yan Ding; Yue-Qing Hu; Shu-Qin Zhan; Cun-Jiang Li; Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Background:The brain stem is found to be impaired in multiple system atrophy-cerebellar types (MSA-C).Rapid eye movement (REM) sleep behavior disorder (RBD) is reported as a marker of progressive brain stem dysfunction.Few systematic studies about the sleep disturbances in MSA-C patients combined with or without RBD were reported.This study aimed to explore the polysomnographic (PSG) features of sleep disturbances between MSA-C patients with and without RBD.Methods:Totally,46 MSA-C patients (23 with RBD,and 23 without RBD) were enrolled in this study.All patients underwent a structured interview for their demographic data,history of sleep pattern,and movement disorders;and then,overnight video-PSG was performed in each patient.All the records were evaluated by specialists at the Sleep Medicine Clinic for RBD and the Movement Disorder Clinic for MSA-C.The Student's t-test,Mann-Whitney U-test for continuous variables,and the Chi-square test for categorical variables were used in this study.Results:MSA-C patients with RBD had younger visiting age (52.6 ± 7.4 vs.56.7 ± 6.0 years,P =0.046) and shorter duration of the disease (12.0 [12.0,24.0] vs.24.0 [14.0,36.0] months,P =0.009) than MSA-C patients without RBD.MSA-C with RBD had shorter REM sleep latency (111.7 ± 48.2 vs.157.0 ± 68.8 min,P =0.042),higher percentage of REM sleep (14.9% ±4.0% vs.10.0% ± 3.2%,P =0.019),and lower Stage Ⅰ (9.5% ±7.2% vs.15.9% ±8.0%,P =0.027) than MSA-C without RBD.Moreover,MSA-C patients with RBD had more decreased sleep efficiency (52.4% ±12.6% vs.65.8% ±15.9%,P =0.029) than that without RBD.Conclusions:In addition to the RBD,MSA-C patients with RBD had other more severe sleep disturbances than those without RBD.The sleep disorders of MSA patients might be associated with the progress of the disease.

  1. Comparison Study of Polysomnographic Features in Multiple System Atrophy-cerebellar Types Combined with and without Rapid Eye Movement Sleep Behavior Disorder

    Science.gov (United States)

    Ding, Yan; Hu, Yue-Qing; Zhan, Shu-Qin; Li, Cun-Jiang; Wang, Hong-Xing; Wang, Yu-Ping

    2016-01-01

    Background: The brain stem is found to be impaired in multiple system atrophy-cerebellar types (MSA-C). Rapid eye movement (REM) sleep behavior disorder (RBD) is reported as a marker of progressive brain stem dysfunction. Few systematic studies about the sleep disturbances in MSA-C patients combined with or without RBD were reported. This study aimed to explore the polysomnographic (PSG) features of sleep disturbances between MSA-C patients with and without RBD. Methods: Totally, 46 MSA-C patients (23 with RBD, and 23 without RBD) were enrolled in this study. All patients underwent a structured interview for their demographic data, history of sleep pattern, and movement disorders; and then, overnight video-PSG was performed in each patient. All the records were evaluated by specialists at the Sleep Medicine Clinic for RBD and the Movement Disorder Clinic for MSA-C. The Student's t-test, Mann-Whitney U-test for continuous variables, and the Chi-square test for categorical variables were used in this study. Results: MSA-C patients with RBD had younger visiting age (52.6 ± 7.4 vs. 56.7 ± 6.0 years, P = 0.046) and shorter duration of the disease (12.0 [12.0, 24.0] vs. 24.0 [14.0, 36.0] months, P = 0.009) than MSA-C patients without RBD. MSA-C with RBD had shorter REM sleep latency (111.7 ± 48.2 vs. 157.0 ± 68.8 min, P = 0.042), higher percentage of REM sleep (14.9% ±4.0% vs. 10.0% ± 3.2%, P = 0.019), and lower Stage I (9.5% ±7.2% vs. 15.9% ±8.0%, P = 0.027) than MSA-C without RBD. Moreover, MSA-C patients with RBD had more decreased sleep efficiency (52.4% ±12.6% vs. 65.8% ±15.9%, P = 0.029) than that without RBD. Conclusions: In addition to the RBD, MSA-C patients with RBD had other more severe sleep disturbances than those without RBD. The sleep disorders of MSA patients might be associated with the progress of the disease. PMID:27625088

  2. Clinico-MRI study of hemispheric disorder in long-term follow-up cases of multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Konagaya, Masaaki; Miwa, Shigeru; Matsuoka, Yukihiko [Suzuka National Hospital, Mie (Japan); Konagaya, Yoko

    1998-12-01

    Twelve cases of multiple system atrophy (MSA) were studied for clinical and MRI findings of the cerebral hemispheric involvement. The subjects consisted of five olivopontocerebellar atrophy (OPCA) type and seven striatonigral degeneration (SND) type. The age at onset was 56.7{+-}8.0 (M{+-}SD) years, duration of illness at the first MRI study 3.2{+-}1.1 years, duration of illness at the last study 8.1{+-}2.2 years, and the following up duration 4.9{+-}2.0 years. The grasping phenomenon was observed in 70% of the cases examined, snout reflex in 80%, slowness of verbal response in 88%, and decrease of spontaneous speech in 100%. Three cases finally fell into the state of mutism. Three out of ten cases were categorized as dementia by HDS-R (Hasegawa Dementia Scale-Revised) test. Besides the progression of the pontocerebellar atrophy and putaminal changes, MRI study revealed progressive frontal lobe atrophy in most cases. At six years after the onset, SND type showed significantly higher incidence of conspicuous frontal lobe atrophy and dilatation of the Sylvian fissure than OPCA type. Cerebral ventricular dilatation was common feature, and atrophy of the temporal and occipital lobes were observed in several cases. We indicated the possible involvement of the cerebral hemisphere, especially the frontal lobe, and higher nervous function in MSA. (author)

  3. [X-linked lymphoproliferative syndrome type 1 complicated with secondary hemophagocytic lymphohistiocytosis and ileal perforation: case report and literature review].

    Science.gov (United States)

    Xiao, L; Guan, X M; Meng, Y; Zhao, X D; Xian, Y; An, Y F; Yu, J

    2016-04-01

    To analyze and summarize the clinical characteristics, laboratory tests and treatment of X-linked lymphoproliferative syndrome type 1 (XLP-1). A retrospective study was done in 2012 on an XLP-1 patient to collect the data on clinical manifestation, laboratory examination, gene and protein expression, complications and prognosis. Literatures were reviewed in Pubmed with the key word"X-linked lymphoproliferative syndrome". The patient with persistent high fever, jaundice, abdominal distension, hepatosplenomegaly and lymphadenectasis, rash and suspicious positive family history; the patient eventually died of hemophagocytic lymphohistiocytosis (HLH), with intestinal perforation, intestinal infection and bleeding after being infected with EB virus. This patient with SH2D1A gene exon 1 large fragment of the coding region of the nucleotide deletion and insertion mutations causing missense mutations (p.Leu25Lys) and nonsense mutations (stop codon TAG was inserted after missense mutation so that the protein encoded by the early termination of the 25 amino acids), which led to SAP protein missing. The expression of SAP in his mother was also partly missing. Retrieval of reports on XLP-1 was conducted through literature search (included totally 157 cases) at home and abroad, positive family history accounted for 60.6%(40/66); lymphoma incidence accounted for 49.7%(72/145); low gamma globulin occurred in 24.8%(39/157) of cases; secondary HLH ratio accounted for 43.3%(68/157); XLP-1 in patients with hemorrhagic enteritis and gastritis was low, accounted for only 2.6%(3/116). XLP-1 patients occasionally develop necrotic enteritis complicated with ileal perforation.XLP-1 with large fragment deletion of SH2D1A gene might be associated with serious gastrointestinal manifestations.

  4. Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder.

    Science.gov (United States)

    Sarachana, Tewarit; Hu, Valerie W

    2013-05-22

    We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as in the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans. Here we identify transcriptional targets of RORA in human neuronal cells on a genome-wide level using chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then validated by an independent ChIP followed by quantitative PCR analysis. To further demonstrate that reduced RORA expression results in reduced transcription of RORA targets, we determined the expression levels of the selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression. The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 2,764 genomic locations corresponding to promoter regions of 2,544 genes across the human genome. Gene ontology analysis of this dataset of genes that are potentially directly regulated by RORA1 reveals statistically significant enrichment in biological functions negatively impacted in individuals with ASD, including neuronal differentiation, adhesion and survival, synaptogenesis, synaptic transmission and plasticity, and axonogenesis, as well as higher level functions such as

  5. Barriers to effective diagnosis and management of a bleeding patient with undiagnosed bleeding disorder across multiple specialties: results of a quantitative case-based survey

    Directory of Open Access Journals (Sweden)

    Reding MT

    2012-10-01

    Full Text Available Mark T Reding,1 David L Cooper21Center for Bleeding and Clotting Disorders, University of Minnesota Medical Center, Minneapolis, MN, 2Medical Affairs, Novo Nordisk Inc, Princeton, NJ, USABackground: Bleeding symptoms commonly seen by multiple physician specialties may belie undiagnosed congenital or acquired bleeding disorders. Acquired hemophilia is a potentially life-threatening cause of unexplained acute bleeding manifested by an abnormal activated partial thromboplastin time (aPTT that does not correct with 1:1 mixing with normal plasma.Methods: Practicing physicians (hematology/oncology, emergency medicine, geriatrics, internal medicine, rheumatology, obstetrics and gynecology, critical care medicine, and general surgery completed an online survey based on a hypothetical case scenario.Results: Excluding surgeons and obstetrician/gynecologist respondents, 302 physicians (about 50 per specialty were presented with an older adult woman complaining of recurrent epistaxis. Nearly 90% ordered a complete blood count and coagulation studies (aPTT, prothrombin time [PT]/international normalized ratio [INR]. Despite a prolonged aPTT of 42 seconds, <50% of nonhematologists would repeat the aPTT, and <45% would consult a hematologist; emergency medicine physicians were least likely (10% and rheumatologists were most likely (43% to consult. After presentation weeks later with bruising and abdominal/back pain, ≥90% of physicians within each specialty ordered a complete blood count or PT/INR/aPTT. Despite an aPTT of 63 seconds, the majority did not repeat the aPTT. At this point, approximately 75% of internal medicine and geriatric physicians indicated they would consult a hematologist, versus 47% in emergency medicine and 50% in critical care. All participants preferred abdominal computed tomography (80%–84%. After 12 hours of additional observation, 73% to 94% of respondents consulted a hematologist. Complete blood count revealed anemia and an a

  6. Magnetic Acupressure in Reducing Pain in Cancer Patients Undergoing Bone Marrow Aspiration and Biopsy

    Science.gov (United States)

    2010-04-09

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  7. Music in Reducing Anxiety and Pain in Adult Patients Undergoing Bone Marrow Biopsy for Hematologic Cancers or Other Diseases

    Science.gov (United States)

    2017-01-18

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Psychosocial Effects of Cancer and Its Treatment

  8. Methadone, Morphine, or Oxycodone in Treating Pain in Patients With Cancer

    Science.gov (United States)

    2012-11-09

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  9. Donor Natural Killer Cells After Donor Stem Cell Transplant in Treating Patients With Advanced Cancer

    Science.gov (United States)

    2013-02-18

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Adult Solid Tumor, Protocol Specific

  10. High-Density Single-Layer Coating of Gold Nanoparticles onto Multiple Substrates by Using an Intrinsically Disordered Protein of α-Synuclein for Nanoapplications.

    Science.gov (United States)

    Bhak, Ghibom; Lee, Junghee; Kim, Chang-Hyun; Chung, Dong Young; Kang, Jin Hyoun; Oh, Soojung; Lee, Jungsup; Kang, Jin Soo; Yoo, Ji Mun; Yang, Jee Eun; Rhoo, Kun Yil; Park, Sunghak; Lee, Somin; Nam, Ki Tae; Jeon, Noo Li; Jang, Jyongsik; Hong, Byung Hee; Sung, Yung-Eun; Yoon, Myung-Han; Paik, Seung R

    2017-03-15

    Functional graffiti of nanoparticles onto target surface is an important issue in the development of nanodevices. A general strategy has been introduced here to decorate chemically diverse substrates with gold nanoparticles (AuNPs) in the form of a close-packed single layer by using an omni-adhesive protein of α-synuclein (αS) as conjugated with the particles. Since the adsorption was highly sensitive to pH, the amino acid sequence of αS exposed from the conjugates and its conformationally disordered state capable of exhibiting structural plasticity are considered to be responsible for the single-layer coating over diverse surfaces. Merited by the simple solution-based adsorption procedure, the particles have been imprinted to various geometric shapes in 2-D and physically inaccessible surfaces of 3-D objects. The αS-encapsulated AuNPs to form a high-density single-layer coat has been employed in the development of nonvolatile memory, fule-cell, solar-cell, and cell-culture platform, where the outlying αS has played versatile roles such as a dielectric layer for charge retention, a sacrificial layer to expose AuNPs for chemical catalysis, a reaction center for silicification, and biointerface for cell attachment, respectively. Multiple utilizations of the αS-based hybrid NPs, therefore, could offer great versatility to fabricate a variety of NP-integrated advanced materials which would serve as an indispensable component for widespread applications of high-performance nanodevices.

  11. What is a Visual Object? Evidence from the Reduced Interference of Grouping in Multiple Object Tracking for Children with Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Lee de-Wit

    2012-05-01

    Full Text Available Objects offer a critical unit with which we can organise our experience of the world. However, whilst their influence on perception and cognition may be fundamental, understanding how objects are constructed from sensory input remains a key challenge for vision research and psychology in general. A potential window into the means by which objects are constructed in the visual system is offered by the influence that they have on the allocation of attention. In Multiple Object Tracking (MOT, for example, attention is automatically allocated to whole objects, even when this interferes with the tracking of the parts of these objects. In this study we demonstrate that this default tendency to track whole objects is reduced in children with Autisim Spectrum Disorders (ASD. This result both validates the use of MOT as a window into how objects are generated in the visual system and highlights how the reduced bias towards more global processing in ASD could influence further stages of cognition by altering the way in which attention selects information for further processing.

  12. Cytokines and HCV-Related Disorders

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2012-01-01

    However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN-gamma-inducible CXC chemokine ligand (CXCL-9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases—mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes—are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-alpha may result in viral clearance during persistent infection and reverts this process.

  13. Multiple structural states exist throughout the helical nucleation sequence of the intrinsically disordered protein stathmin, as reported by electron paramagnetic resonance spectroscopy.

    Science.gov (United States)

    Chui, Ashley J; López, Carlos J; Brooks, Evan K; Chua, Katherina C; Doupey, Tonia G; Foltz, Gretchen N; Kamel, Joseph G; Larrosa, Estefania; Sadiki, Amissi; Bridges, Michael D

    2015-03-10

    The intrinsically disordered protein (IDP) stathmin plays an important regulatory role in cytoskeletal maintenance through its helical binding to tubulin and microtubules. However, it lacks a stable fold in the absence of its binding partner. Although stathmin has been a focus of research over the past two decades, the solution-phase conformational dynamics of this IDP are poorly understood. It has been reported that stathmin is purely monomeric in solution and that it bears a short helical region of persistent foldedness, which may act to nucleate helical folding in the C-terminal direction. Here we report a comprehensive study of the structural equilibria local to this region in stathmin that contradicts these two claims. Using the technique of electron paramagnetic resonance (EPR) spectroscopy on spin-labeled stathmin mutants in the solution-phase and when immobilized on Sepharose solid support, we show that all sites in the helical nucleation region of stathmin exhibit multiple spectral components that correspond to dynamic states of differing mobilities and stabilities. Importantly, a state with relatively low mobility dominates each spectrum with an average population greater than 50%, which we suggest corresponds to an oligomerized state of the protein. This is in contrast to a less populated, more mobile state, which likely represents a helically folded monomeric state of stathmin, and a highly mobile state, which we propose is the random coil conformer of the protein. Our interpretation of the EPR data is confirmed by further characterization of the protein using the techniques of native and SDS PAGE, gel filtration chromatography, and multiangle and dynamic light scattering, all of which show the presence of oligomeric stathmin in solution. Collectively, these data suggest that stathmin exists in a diverse equilibrium of states throughout the purported helical nucleation region and that this IDP exhibits a propensity toward oligomerization.

  14. Development of multiple myeloma in a patient with chronic hepatitis C: A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Peter Laszlo Lakatos; Sandor Fekete; Margit Horanyi; Simon Fischer; Margit E Abonyi

    2006-01-01

    An association between chronic hepatitis C virus (HCV)infection and essential mixed cryoglobulinaemia and nonHodgkin lymphoma (NHL) has been suggested. However,a causative role of HCV in these conditions has not been established. The authors report a case of a 50 year-old woman with chronic hepatitis C (CHC) who has been followed up since 1998 due to a high viral load, genotype 1b and moderately elevated liver function tests (LFTs).Laboratory data and liver biopsy revealed moderate activity (grade: 5/18, stage: 1/6). In April 1999, one-year interferon therapy was started. HCV-RNA became negative with normalization of LFTs. However, the patient relapsed during treatment. In September 2002, the patient was admitted for chronic back pain. A CT examination demonstrated degenerative changes. In March 2003,multiple myeloma was diagnosed (IgG-kappa, bone marrow biopsy: 50% plasma cell infiltration). MRI revealed a compression fracture of the 5th lumbar vertebral body and an abdominal mass in the right lower quadrant, infiltrating the canalis spinalis. Treatment with vincristine,adriamycin and dexamethasone (VAD) was started and bisphosphonate was administered regularly. In January 2004, after six cycles of VAD therapy, the multiple myeloma regressed. Thalidomide, as a second line treatment of refractory multiple myeloma (MM) was initiated,and followed by peginterferon-α2b and ribavirin against the HCV infection in June. In June 2005, LFTs returned to normal, while HCV-RNA was negative, demonstrating an end of treatment response. Although a pathogenic role of HCV infection in malignant lymphoproliferative disorders has not been established, NHL and possibly MM may develop in CHC patients, supporting a role of a complex follow-up in these patients.

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

    Science.gov (United States)

    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.

  16. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract after treatment with adalimumab in resistant Crohn's colitis.

    Science.gov (United States)

    Edison, Natalia; Belhanes-Peled, Hila; Eitan, Yuval; Guthmann, Yifat; Yeremenko, Yelena; Raffeld, Mark; Elmalah, Irit; Trougouboff, Philippe

    2016-11-01

    We report a case of intestinal indolent T-cell lymphoproliferative disease (TCLPD) occurring after the initiation of tumor necrosis factor-α (TNF-α) inhibitor therapy for resistant Crohn's disease. A prominent T-cell infiltrate positive for CD8, TIA-1, and T-cell receptor-βF1 was associated with the foci of active inflammation. T-cell receptor gene clonality studies (BIOMED-2) demonstrated monoclonality. After the TNF-α inhibitor treatment was withdrawn, the T-cell infiltrates regressed, but 2 years later, the same monoclonal T-cell infiltrate reappeared at the only site of active inflammation. To the best of our knowledge, this report is the first to show a link between active inflammation and the TCLPD. In addition, it suggests a possible influence of the TNF-α inhibitor treatment on the evolution of the TCLPD. A high degree of suspicion is required in the presence of any unusual lymphoid infiltrate in inflammatory bowel disease to avoid overlooking an indolent TCLPD or misdiagnose an aggressive lymphoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease.

    Science.gov (United States)

    Rivat, Christine; Booth, Claire; Alonso-Ferrero, Maria; Blundell, Michael; Sebire, Neil J; Thrasher, Adrian J; Gaspar, H Bobby

    2013-02-14

    X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SLAM-associated protein (SAP) and leads to abnormalities of NKT-cell development, NK-cell cytotoxicity, and T-dependent humoral function. Curative treatment is limited to allogeneic hematopoietic stem cell (HSC) transplantation. We tested whether HSC gene therapy could correct the multilineage defects seen in SAP(-/-) mice. SAP(-/-) murine HSCs were transduced with lentiviral vectors containing either SAP or reporter gene before transplantation into irradiated recipients. NKT-cell development was significantly higher and NK-cell cytotoxicity restored to wild-type levels in mice receiving the SAP vector in comparison to control mice. Baseline immunoglobulin levels were significantly increased and T-dependent humoral responses to NP-CGG, including germinal center formation, were restored in SAP-transduced mice.We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP(-/-) mice providing proof of concept for gene therapy in XLP1.

  18. 多系统萎缩患者的主客观睡眠障碍%Subjective and objective features of sleep disorders in multiple system atrophy

    Institute of Scientific and Technical Information of China (English)

    赵馨; 张玉虎; 冯淑君; 聂坤; 王丽敏; 张又文; 谢泗芬; 李彦; 周晓红

    2016-01-01

    目的 研究多系统萎缩(MSA)患者的主客观睡眠障碍.方法 选取2013年6月至2015年8月广东省人民医院神经内科住院的MSA患者30例,对照组25例,采用非运动症状量表睡眠分项、匹兹堡睡眠质量指数(PSQI)及帕金森病睡眠量表-2(PDSS-2)评价其主观睡眠障碍,同时行多导睡眠图(PSG)评价其客观睡眠障碍.结果 30例MSA患者中有29例(96.7%)至少存在1项睡眠障碍主诉.MSA组的PSQI总分(分)、PDSS-2总分(分)较对照组显著增高(PSQI:9.37±4.60和5.36±2.86,t=-3.934,P<0.01;PDSS-2:15.60±10.02和5.48±2.74,t=-5.300,P <0.01),MSA组睡眠量表的部分因子分与增龄、运动症状相关.PSG示MSA组患者总睡眠时间减少,睡眠效率减低,各期睡眠比例未见差异;确诊快速动眼睡眠行为障碍(RBD)者24例(80.0%),其中仅2例表现为暴力动作;MSA组周期性肢体运动(PLMS)指数增高.以帕金森症候群为主的MSA (MSA-P)组PDSS-2总分较以共济失调为主的MSA (MSA-C)组增高(17.79±10.01和6.83±2.40,t=4.834,P<0.01).结论 MSA患者存在多种睡眠障碍;其睡眠结构改变以睡眠时长减少、睡眠效率减低为主,各期睡眠比例变化不明显;RBD发生率高而症状轻;PLMS在MSA患者多见且程度较重;MSA-P患者的睡眠主观体验与运动症状相关,且较MSA-C患者更差.%Objective To investigate the subjective and objective sleep disorders in patients with multiple system atrophy (MSA).Methods Thirty MSA patients and 25 age-and-sex matched controls were enrolled.Sleep disorders were assessed by Pittsburgh Sleep Quality Index (PSQI),Parkinson's Disease Sleep Scale-2 (PDSS-2),and polysomnography (PSG).Results Twenty-nine (96.7%) patients complained of sleep disorders.The PSQI and PDSS-2 scores were significantly higher in MSA group than those in control group (PSQI:9.37 ±4.60 vs 5.36 ±2.86,t =-3.934,P <0.01 ;PDSS-2:15.60 ± 10.02 vs 5.48 ±2.74,t =-5.300,P < 0.01).Some parameters of sleep scales were

  19. Molecular analysis of immunoglobulin genes in multiple myeloma.

    Science.gov (United States)

    Kosmas, C; Stamatopoulos, K; Stavroyianni, N; Belessi, C; Viniou, N; Yataganas, X

    1999-04-01

    The study of immunoglobulin genes in multiple myeloma over the last five years has provided important information regarding biology, ontogenetic location, disease evolution, pathogenic consequences and tumor-specific therapeutic intervention with idiotypic vaccination. Detailed analysis of V(H) genes has revealed clonal relationship between switch variants expressed by the bone marrow plasma cell and myeloma progenitors in the marrow and peripheral blood. V(H) gene usage is biased against V4-34 (encoding antibodies with cold agglutinin specificity; anti-l/i) explaining the absence of autoimmune phenomena in myeloma compared to other B-cell lymphoproliferative disorders. V(H) genes accumulate somatic hypermutations following a distribution compatible with antigen selection, but with no intraclonal heterogeneity. V(L) genes indicate a bias in usage of VkappaI family members and somatic hypermutation, in line with antigen selection, of the expressed Vkappa genes is higher than any other B-cell lymphoid disorder. A complementary imprint of antigen selection as evidenced by somatic hypermutation of either the V(H) or V(L) clonogenic genes has been observed. The absence of ongoing somatic mutations in either V(H) or V(L) genes gives rise to the notion that the cell of origin in myeloma is a post-germinal center memory B-cell. Clinical application of sensitive PCR methods in order to detect clonal immunoglobulin gene rearrangements has made relevant the monitoring and follow-up of minimal residual disease in stem cell autografts and after myeloablative therapy. The fact that surface immunoglobulin V(H) and V(L) sequences constitute unique tumor-specific antigenic determinants has stimulated investigators to devise strategies aiming to generate active specific immunity against the idiotype of malignant B-cells in myeloma by constructing vaccines based on expressed single-chain Fv fragments, DNA plasmids carrying V(H)+V(L) clonogenic genes for naked DNA vaccination, or

  20. Quantum Interference of Multiple Beams Induced by Multiple Scattering

    DEFF Research Database (Denmark)

    Ott, Johan Raunkjær; Mortensen, N. Asger; Lodahl, Peter

    2011-01-01

    We report on quantum interference induced by the transmission of quantized light through a multiple-scattering medium. We show that entangled states can be created by multiple-scattering and that quantum interference survives disorder averaging.......We report on quantum interference induced by the transmission of quantized light through a multiple-scattering medium. We show that entangled states can be created by multiple-scattering and that quantum interference survives disorder averaging....

  1. Dissociative Identity Disorder

    Science.gov (United States)

    Schmidt, Tom

    2007-01-01

    Few psychological disorders in the Diagnostic Statistical Manual have generated as much controversy as Dissociative Identity Disorder (DID). For the past 35 years diagnoses of DID, previously referred to as Multiple Personality Disorder (MPD), have increased exponentially, causing various psychological researchers and clinicians to question the…

  2. Current Status of Older and New Purine Nucleoside Analogues in the Treatment of Lymphoproliferative Diseases

    Directory of Open Access Journals (Sweden)

    Pawel Robak

    2009-03-01

    Full Text Available For the past few years more and more new cytotoxic agents active in the treatment of hematological malignancies have been synthesized and become available for either in vitro studies or clinical trials. Among them the class of antineoplastic drugs belonging to the purine nucleoside analogues group (PNAs plays an important role. Three of them: pentostatin (DCF, cladribine (2-CdA and fludarabine (FA were approved by Food and Drug Administration (FDA for the treatment of hematological malignancies. Recently three novel PNAs: clofarabine (CAFdA, nelarabine (ara-G and forodesine (immucillin H, BCX-1777 have been synthesized and introduced into preclinical studies and clinical trials. These agents seem to be useful mainly for the treatment of human T-cell proliferative disorders and they are currently undergoing clinical trials in lymphoid malignancies. However, there are also several studies suggesting the role of these drugs in B-cell malignancies. This review will summarize current knowledge concerning the mechanism of action, pharmacologic properties, clinical activity and toxicity of PNAs accepted for use in clinical practice, as well as new agents available for clinical trials.

  3. Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging.

    Science.gov (United States)

    Wester, Hans Jürgen; Keller, Ulrich; Schottelius, Margret; Beer, Ambros; Philipp-Abbrederis, Kathrin; Hoffmann, Frauke; Šimeček, 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 [(68)Ga]Pentixafor in mice bearing human lymphoma xenografts as an exemplary CXCR4-expressing tumor entity, we report on the first clinical applications of [(68)Ga]Pentixafor-Positron Emission Tomography as a powerful method for CXCR4 imaging in cancer patients. [(68)Ga]Pentixafor binds with high affinity and selectivity to human CXCR4 and exhibits a favorable dosimetry. [(68)Ga]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.

  4. Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients.

    Science.gov (United States)

    Morra, M; Simarro-Grande, M; Martin, M; Chen, A S; Lanyi, A; Silander, O; Calpe, S; Davis, J; Pawson, T; Eck, M J; Sumegi, J; Engel, P; Li, S C; Terhorst, C

    2001-09-28

    X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency characterized by extreme susceptibility to Epstein-Barr virus. The XLP disease gene product SH2D1A (SAP) interacts via its SH2 domain with a motif (TIYXXV) present in the cytoplasmic tail of the cell-surface receptors CD150/SLAM, CD84, CD229/Ly-9, and CD244/2B4. Characteristically, the SH2D1A three-pronged interaction with Tyr(281) of CD150 can occur in absence of phosphorylation. Here we analyze the effect of SH2D1A protein missense mutations identified in 10 XLP families. Two sets of mutants were found: (i) mutants with a marked decreased protein half-life (e.g. Y7C, S28R, Q99P, P101L, V102G, and X129R) and (ii) mutants with structural changes that differently affect the interaction with the four receptors. In the second group, mutations that disrupt the interaction between the SH2D1A hydrophobic cleft and Val +3 of its binding motif (e.g. T68I) and mutations that interfere with the SH2D1A phosphotyrosine-binding pocket (e.g. C42W) abrogated SH2D1A binding to all four receptors. Surprisingly, a mutation in SH2D1A able to interfere with Thr -2 of the CD150 binding motif (mutant T53I) severely impaired non-phosphotyrosine interactions while preserving unaffected the binding of SH2D1A to phosphorylated CD150. Mutant T53I, however, did not bind to CD229 and CD224, suggesting that SH2D1A controls several critical signaling pathways in T and natural killer cells. Because no correlation is present between identified types of mutations and XLP patient clinical presentation, additional unidentified genetic or environmental factors must play a strong role in XLP disease manifestations.

  5. P-glycoprotein is expressed and causes resistance to chemotherapy in EBV-positive T-cell lymphoproliferative diseases.

    Science.gov (United States)

    Yoshimori, Mayumi; Takada, Honami; Imadome, Ken-Ichi; Kurata, Morito; Yamamoto, Kouhei; Koyama, Takatoshi; Shimizu, Norio; Fujiwara, Shigeyoshi; Miura, Osamu; Arai, Ayako

    2015-10-01

    Epstein-Barr virus-positive T-cell lymphoproliferative diseases (EBV-T-LPDs) are rare lymphomas with poor prognosis. Although chemotherapeutic strategies such as CHOP have been often selected, they have exhibited only limited efficacy. To clarify the mechanism of chemoresistance, we examined P-glycoprotein (P-gp) expression. P-gp acts as an energy-dependent efflux pump that excretes drugs from the cytoplasm, resulting in low-intracellular drug concentrations and poor sensitivity to chemotherapy. We examined P-gp expression in EBV-positive cells by immunohistochemistry staining in three patients of EBV-T-LPDs and the expression was detected in all patients. We also examined mdr1 mRNA expression by reverse-transcriptase polymerase-chain reaction (RT-PCR) in EBV-positive tumor cells from these patients and additional three patients. The expression was detected in all examined patients. In five EBV-T-LPDs patients, P-gp function was detected by Rhodamine-123 efflux assay in these cells. The efflux was inhibited by treatment with a P-gp inhibitor, cyclosporine A (CsA). We also examined and detected P-gp expression in EBV-positive T-cell lines SNT8 and SNT16 established from EBV-T-LPDs patients, by RT-PCR and western blotting. The function was also detected by Rhodamine-123 efflux in these cell lines. Inhibition and knock down of P-gp by CsA and siRNA, respectively, enhanced etoposide- and doxorubicin-induced cell death in the EBV-positive T-cell lines. Finally, we infected the T-cell line MOLT4 with EBV, and found that mdr1 mRNA expression and Rhodamine 123 efflux were upregulated after infection. These results indicated that enhanced P-gp expression contributed to the chemoresistance of EBV-T-LPDs.

  6. NFkB is activated by multiple mechanisms in hairy cell leukemia.

    Science.gov (United States)

    Nagel, Stefan; Ehrentraut, Stefan; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G; MacLeod, Roderick A F

    2015-07-01

    Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder of unclear pathogenesis. Recent studies have identified BRAF(V600E) mutations in most HCL patients, highlighting this abnormality as a molecular hallmark for this disease. Cell lines originating from HCL patients lack BRAF mutations but retain the typical piliferous morphology and the distinctive HCL immunophenotype, thus, constituting suitable tools for identifying alternative tumor genes and leukemic mechanisms in this malignancy. To this end, we integrated genomic and transcriptional profiling of the HCL cell line MLMA. The expression levels of genomically targeted genes were compared to four HCL control cell lines, thus, identifying 91 chromosomally deregulated genes. Gene set enrichment analysis of these indicted apoptosis, proliferation, and DNA damage response as altered processes. Accordingly, prominent target genes overexpressed in this cell line include ATM, BRAF, CDK6, CUTL1/CUX1, H2AFX, and REL. Treatment of MLMA with selective pharmacological inhibitors and specific siRNA-mediated gene knockdowns highlighted a central role for NFkB in their deregulation in HCL. Moreover, relevant expression profiling data from HCL and ABC-DLBCL cell lines display elevated NFkB-pathway activity when compared to GC-DLBCL equivalents. Finally, analysis of HCL patient samples in silico collectively supported the clinical significance of NFkB activation in this disease. In conclusion, we identified deregulated genes and multiple mechanisms underlying aberrantly activated NFkB-pathway in HCL. Therefore, NFkB may represent a B-cell specific hallmark of HCL and a promising novel therapeutic target, most notably in patients lacking BRAF mutations in this entity including variant HCL.

  7. Genetics Home Reference: multiple system atrophy

    Science.gov (United States)

    ... Home Health Conditions multiple system atrophy multiple system atrophy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Multiple system atrophy is a progressive brain disorder that affects movement ...

  8. A Fas(hi) Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation.

    Science.gov (United States)

    Menezes, Soraya Maria; Leal, Fabio E; Dierckx, Tim; Khouri, Ricardo; Decanine, Daniele; Silva-Santos, Gilvaneia; Schnitman, Saul V; Kruschewsky, Ramon; López, Giovanni; Alvarez, Carolina; Talledo, Michael; Gotuzzo, Eduardo; Nixon, Douglas F; Vercauteren, Jurgen; Brassat, David; Liblau, Roland; Vandamme, Anne Mieke; Galvão-Castro, Bernardo; Van Weyenbergh, Johan

    2017-01-01

    Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fas(hi) T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation, and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC), and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fas(hi) cells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation upon in vitro culture, but not to proviral load. This Fas(hi) phenotype is HAM/TSP-specific, since both ex vivo and in vitro Fas expression was increased as compared to multiple sclerosis (MS), another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signaling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e., blocking vs. triggering Fas receptor in vitro with antagonist and agonist-, anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis

  9. PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative response in the CD19+ B cell compartment

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Alok R. [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Peirce, Susan K. [Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (United States); Joshi, Shweta [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Durden, Donald L., E-mail: ddurden@ucsd.edu [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Division of Pediatric Hematology-Oncology, UCSD Rady Children' s Hospital, La Jolla, CA (United States)

    2014-09-10

    -3 kinase inhibitors reverse the lymphoproliferative phenotype in vivo. - Highlights: • First genetic evidence that PTEN controls LPS/TLR4 signaling in B lymphocytes. • Evidence that PTEN regulates LPS induced lymphoproliferation in vivo. • PI-3 kinase inhibitors block LPS induced lymphoproliferation in vivo.

  10. The Single and Combined Effects of Multiple Intensities of Behavior Modification and Methylphenidate for Children with Attention Deficit Hyperactivity Disorder in a Classroom Setting

    Science.gov (United States)

    Fabiano, Gregory A.; Pelham, William E., Jr.; Gnagy, Elizabeth M.; Burrows-MacLean, Lisa; Coles, Erika K.; Chacko, Anil; Wymbs, Brian T.; Walker, Kathryn S.; Arnold, Fran; Garefino, Allison; Keenan, Jenna K.; Onyango, Adia N.; Hoffman, Martin T.; Massetti, Greta M.; Robb, Jessica A.

    2007-01-01

    Currently behavior modification, stimulant medication, and combined treatments are supported as evidence-based interventions for attention deficit hyperactivity disorder in classroom settings. However, there has been little study of the relative effects of these two modalities and their combination in classrooms. Using a within-subject design, the…

  11. The Single and Combined Effects of Multiple Intensities of Behavior Modification and Methylphenidate for Children with Attention Deficit Hyperactivity Disorder in a Classroom Setting

    Science.gov (United States)

    Fabiano, Gregory A.; Pelham, William E., Jr.; Gnagy, Elizabeth M.; Burrows-MacLean, Lisa; Coles, Erika K.; Chacko, Anil; Wymbs, Brian T.; Walker, Kathryn S.; Arnold, Fran; Garefino, Allison; Keenan, Jenna K.; Onyango, Adia N.; Hoffman, Martin T.; Massetti, Greta M.; Robb, Jessica A.

    2007-01-01

    Currently behavior modification, stimulant medication, and combined treatments are supported as evidence-based interventions for attention deficit hyperactivity disorder in classroom settings. However, there has been little study of the relative effects of these two modalities and their combination in classrooms. Using a within-subject design, the…

  12. Integrating Case Topics in Medical School Curriculum to Enhance Multiple Skill Learning: Using Fetal Alcohol Spectrum Disorders as an Exemplary Case

    Science.gov (United States)

    Paley, Blair; O'Connor, Mary J.; Baillie, Susan J.; Guiton, Gretchen; Stuber, Margaret L.

    2009-01-01

    Objectives: This article describes the use of fetal alcohol spectrum disorders (FASDs) as a theme to connect the learning of basic neurosciences with clinical applications across the age span within a systems-based, integrated curricular structure that emphasizes problem-based learning. Methods: In collaboration with the Centers for Disease…

  13. Adducts of hexamethylenetetramine with ferrocenecarboxylic acid and ferrocene-1,1'-dicarboxylic acid: multiple disorder in space groups Fmm2 and Cmcm.

    Science.gov (United States)

    Zakaria, Choudhury M; Ferguson, George; Lough, Alan J; Glidewell, Christopher

    2003-07-01

    Hexamethylenetetramine, C(6)H(12)N(4), and ferrocenecarboxylic acid, C(11)H(10)FeO(2), form a 1:2 adduct, (I), which is a salt, viz. hexamethylenetetraminium(2+) bis(ferrocenecarboxylate), (C(6)H(14)N(4))[Fe(C(5)H(5))(C(6)H(4)O(2))](2). The dication in (I) is disordered with two orientations at a site of mm2 symmetry in space group Fmm2, while the anion lies across a mirror plane with its unsubstituted cyclopentadienyl ring disordered over two sets of sites. With ferrocene-1,1'-dicarboxylic acid, C(12)H(10)FeO(4), hexamethylenetetramine forms a 1:1 adduct, (II), in which both components are neutral, viz. hexamethylenetetramine-ferrocene-1,1'-dicarboxylic acid (1/1), [Fe(C(6)H(5)O(2))(2)].C(6)H(12)N(4). The amine component in (II) is disordered with two orientations at a site of mm2 symmetry in space group Cmcm, while the acid component is disordered with two orientations at a site of 2/m symmetry. The components in (I) are linked into a finite three-ion aggregate by a single N-H.O hydrogen bond, while the components of (II) are linked into continuous chains by a single O-H.N hydrogen bond.

  14. Schema therapy as treatment for adults with autism spectrum disorder and comorbid personality disorder : Protocol of a multiple-baseline case series study testing cognitive-behavioral and experiential interventions

    NARCIS (Netherlands)

    Vuijk, R.; Arntz, A.

    Background To our knowledge treatment of personality disorder (PD) comorbidity in adults with ASD is understudied and is still in its infancy. This study investigates the effectiveness of schema therapy for PD-psychopathology in adult patients with both ASD and PD. Methods/design Twelve adult

  15. Multiple Pregnancy

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Multiple Pregnancy Home For Patients Search FAQs Multiple Pregnancy Page ... Multiple Pregnancy FAQ188, July 2015 PDF Format Multiple Pregnancy Pregnancy How does multiple pregnancy occur? What are ...

  16. Tongue Disorders

    Science.gov (United States)

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  17. Mental Disorders

    Science.gov (United States)

    Mental disorders include a wide range of problems, including Anxiety disorders, including panic disorder, obsessive-compulsive disorder, post- ... disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history may play a ...

  18. Multiple sclerosis; Multiple Sklerose

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P. [Universitaet des Saarlandes, Abteilung fuer Diagnostische und Interventionelle Neuroradiologie, Radiologische Klinik, Homburg/Saar (Germany); Shariat, K. [Universitaet des Saarlandes, Klinik fuer Neurochirurgie, Homburg/Saar (Germany); Kostopoulos, P. [Universitaet des Saarlandes, Klinik fuer Neurologie, Homburg/Saar (Germany)

    2008-06-15

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [German] Die Multiple Sklerose (MS) ist die haeufigste chronisch-entzuendliche Erkrankung des Myelins mit eingesprengten Laesionen im Bereich der weissen Substanz des zentralen Nervensystems. Die Magnetresonanztomographie (MRT) hat bei der Diagnosestellung und Verlaufskontrolle eine Schluesselrolle. Dieser Artikel befasst sich mit Hauptcharakteristika der MR-Bildbebung. (orig.)

  19. Analyzing subcomponents of affective dysregulation in borderline personality disorder in comparison to other clinical groups using multiple e-diary datasets.

    Science.gov (United States)

    Santangelo, P S; Limberger, M F; Stiglmayr, C; Houben, M; Coosemans, J; Verleysen, G; Kuppens, P; Tuerlinckx, F; Vanpaemel, W; Ebner-Priemer, U W

    2016-01-01

    Affective dysregulation is widely regarded as being the core problem in patients with borderline personality disorder (BPD). Moreover, BPD is the disorder mainly associated with affective dysregulation. However, the empirical confirmation of the specificity of affective dysregulation for BPD is still pending. We used a validated approach from basic affective science that allows for simultaneously analyzing three interdependent components of affective dysregulation that are disturbed in patients with BPD: homebase, variability, and attractor strength (return to baseline). We applied two types of multilevel models on two e-diary datasets to investigate group differences regarding three subcomponents between BPD patients (n = 43; n = 51) and patients with posttraumatic stress disorder (PTSD; n = 28) and those with bulimia nervosa (BN; n = 20) as clinical control groups in dataset 1, and patients with panic disorder (PD; n = 26) and those with major depression (MD; n = 25) as clinical control groups in dataset 2. In addition, healthy controls (n = 28; n = 40) were included in the analyses. In both studies, e-diaries were used to repeatedly collect data about affective experiences during participants' daily lives. In study 1 a high-frequency sampling strategy with assessments in 15 min-intervals over 24 h was applied, whereas the assessments occurred every waking hour over 48 h in study 2. The local ethics committees approved both studies, and all participants provided written informed consent. In contradiction to our hypotheses, BPD patients did not consistently show altered affective dysregulation compared to the clinical patient groups. The only differences in affective dynamics in BPD patients emerged with regard to one of three subcomponents, affective homebase. However, these results were not even consistent. Conversely, comparing the patients to healthy controls revealed a pattern of more negative affective homebases, higher

  20. Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell--depleted SCT

    NARCIS (Netherlands)

    van Esser, J W; van der Holt, B; Meijer, E; Niesters, H G; Trenschel, R; Thijsen, S F; van Loon, A M; Frassoni, F; Bacigalupo, A; Schaefer, U W; Osterhaus, A D; Gratama, J W; Löwenberg, B; Verdonck, L F; Cornelissen, J J

    2001-01-01

    Reactivation of the Epstein-Barr virus (EBV) after allogeneic stem cell transplantation (allo-SCT) may evoke a protective cellular immune response or may be complicated by the development of EBV-lymphoproliferative disease (EBV-LPD). So far, very little is known about the incidence, recurrence, and