Sample records for thrombocytopenic purpura targeting

  1. Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

    ClinicalTrials.gov

    2015-02-09

    Thrombotic Thrombocytopenic Purpura; Congenital Thrombotic Thrombocytopenic Purpura; Familial Thrombotic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura, Congenital; Upshaw-Schulman Syndrome

  2. Idiopathic thrombocytopenic purpura.

    PubMed

    Kayal, L; Jayachandran, S; Singh, Khushboo

    2014-07-01

    Idiopathic thrombocytopenic purpura (ITP) is defined as a hematologic disorder, characterized by isolated thrombocytopenia without a clinically apparent cause. The major causes of accelerated platelet consumption include immune thrombocytopenia, decreased bone marrow production, and increased splenic sequestration. The clinical presentation may be acute with severe bleeding, or insidious with slow development with mild or no symptoms. The initial laboratory tests useful at the first visit to predict future diagnosis were erythrocyte count, leukocyte count, anti-glycoprotein IIb/IIIa antibodies, reticulated platelets, plasma thrombopoietin level. Treatment should be restricted to those patients with moderate or severe thrombocytopenia who are bleeding or at risk of bleeding. We present a case report on ITP with clinical presentation, diagnosis and management. PMID:25191085

  3. Idiopathic thrombocytopenic purpura

    PubMed Central

    Kayal, L.; Jayachandran, S.; Singh, Khushboo

    2014-01-01

    Idiopathic thrombocytopenic purpura (ITP) is defined as a hematologic disorder, characterized by isolated thrombocytopenia without a clinically apparent cause. The major causes of accelerated platelet consumption include immune thrombocytopenia, decreased bone marrow production, and increased splenic sequestration. The clinical presentation may be acute with severe bleeding, or insidious with slow development with mild or no symptoms. The initial laboratory tests useful at the first visit to predict future diagnosis were erythrocyte count, leukocyte count, anti-glycoprotein IIb/IIIa antibodies, reticulated platelets, plasma thrombopoietin level. Treatment should be restricted to those patients with moderate or severe thrombocytopenia who are bleeding or at risk of bleeding. We present a case report on ITP with clinical presentation, diagnosis and management. PMID:25191085

  4. [Idiopathic thrombocytopenic purpura].

    PubMed

    Fujimura, Kingo

    2013-08-01

    In many extragastric manifestations with Helicobacter pylori (HP) infection, the most convincing evidences were observed in idiopathic thrombocytopenic purpura (ITP). The prevalence of HP infection in ITP was not different to general population. The high association of HP infection in ITP was reported in Italy and Japan but low in USA and UK. After eradication therapy, platelet counts response was found in over 50% of ITP cases in Japan and Italy, and about 40% in other countries. The platelet counts response following eradication was maintain for long time with drug free and the relapse case was rare. The platelet elevation reaction by eradication was not influenced by previous treatment, sex and age, but the disease duration as ITP and the platelet count before eradication were controversial factors. The main side effects of eradication were diarrhea, vomiting and skin rash. Based on these evidences, ITP guideline in Japan (2012) recommended that eradication therapy was the first choice treatment for HP positive ITP cases. PMID:23967676

  5. Management of adult idiopathic thrombocytopenic purpura.

    PubMed

    Nakhoul, Ibrahim N; Kozuch, Peter; Varma, Mala

    2006-02-01

    Idiopathic thrombocytopenic purpura (ITP) is defined as isolated thrombocytopenia without a clinically apparent cause. It is categorized as acute, chronic, and refractory. Its clinical presentation ranges from acute to insidious and the bleeding may vary from minimal to severe. The target platelet count with therapy is more than 30,000/microL in sedentary individuals. Since studies regarding therapies for ITP have been mostly uncontrolled case series, the treatment recommendations are largely derived from expert opinion. This review paper summarizes the data on available therapies for adult acute and chronic/refractory ITP. The therapies include splenectomy, steroids, intravenous immunoglobulin, anti-Rh(D), monoclonal antibodies, danazol, chemotherapy, plasma exchange, and others. PMID:16728922

  6. Treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Fontana, S; Kremer Hovinga, J A; Lämmle, B; Mansouri Taleghani, B

    2006-05-01

    Thrombotic thrombocytopenic purpura (TTP), characterized by thrombocytopenia and microangiopathic haemolytic anaemia, was almost universally fatal until the introduction of plasma exchange (PE) therapy in the 1970s. Based on clinical studies, daily PE has become the first-choice therapy since 1991. Recent findings may explain its effectiveness, which may include, in particular, the removal of anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor multimers and/or supply of ADAMTS13 in acquired idiopathic or congenital TTP. Based on currently available data, the favoured PE regimen is daily PE [involving replacement of 1-1.5 times the patient's plasma volume with fresh-frozen plasma (FFP)] until remission. Adverse events of treatment are mainly related to central venous catheters. The potential reduction of plasma related side-effects, such as transfusion-related acute lung injury (TRALI) or febrile transfusion reactions by use of solvent-detergent treated (S/D) plasma instead of FFP is not established by controlled clinical studies. Uncontrolled clinical observations and the hypothesis of an autoimmune process in a significant part of the patients with acquired idiopathic TTP suggest a beneficial effect of adjunctive therapy with corticosteroids. Other immunosuppressive treatments are not tested in controlled trials and should be reserved for refractory or relapsing disease. There is no convincing evidence for the use of antiplatelet agents. Supportive treatment with transfusion of red blood cells or platelets has to be evaluated on a clinical basis, but the transfusion trigger for platelets should be very restrictive. Further controlled, prospective studies should consider the different pathophysiological features of thrombotic microangiopathies, address the prognostic significance of ADAMTS13 and explore alternative exchange fluids to FFP, the role of immunosuppressive therapies and of new plasma saving approaches as recombinant ADAMTS13 and protein A immunoadsorption. PMID:16635066

  7. AMEGAKARYOCYTIC THROMBOCYTOPENIC PURPURA : A FIFTEEN YEAR EXPERIENCE

    Microsoft Academic Search

    B. Shafayan; A. Khodabandeh; M. Keyhani; M. Bakhshi

    Amegakaryocytic thrombocytopenia, a rare variation of bone marrow aplasia, has been described in association with viral infection, vaccination, alcoholism and drug-toxicity. In the present study, we presented 20 cases of amegakaryocytic thrombocytopenic purpura in a cohort of Iranian patients presented to hematology clinics of two university hospitals with mucocutaneous bleeding. Complete blood counts, reticulocyte counts and repeated bone marrow aspiration\\/biopsy

  8. Candida albicans-Induced Chronic Thrombocytopenic Purpura

    Microsoft Academic Search

    Khaldoon M. Alawneh

    2011-01-01

    We present 2 patients with chronic immune thrombocytopenic purpura (ITP) secondary to Candida albicans infection. Neither patient responded to standard ITP therapy including splenectomy. Appropriate antifungal treatment of the C. albicans infection was followed by sustained improvement in platelet count in both patients. To our knowledge, this is the first report of ITP in association with C. albicans infection.

  9. Candida albicans-induced chronic thrombocytopenic purpura.

    PubMed

    Ayesh Haj Yousef, Mahmoud H; Alawneh, Khaldoon M

    2011-01-01

    We present 2 patients with chronic immune thrombocytopenic purpura (ITP) secondary to Candida albicans infection. Neither patient responded to standard ITP therapy including splenectomy. Appropriate antifungal treatment of the C. albicans infection was followed by sustained improvement in platelet count in both patients. To our knowledge, this is the first report of ITP in association with C. albicans infection. PMID:21860227

  10. Postoperative thrombotic thrombocytopenic purpura after aortofemoral bypass

    PubMed Central

    Mainali, Naba R.; Aryal, Madan R.; Badal, Madan; Bhatt, Vijaya R.; Alweis, Richard

    2013-01-01

    Thrombotic thrombocytopenic purpura (TTP) is uncommon in the postoperative setting, even more so after vascular surgery. We present a case of thrombocytopenia after aortofemoral bypass, which highlights the importance of a high index of suspicion for postoperative TTP to avoid life-threatening consequences. PMID:23882385

  11. [Pregnancy and labor in idiopathic thrombocytopenic purpura].

    PubMed

    Tampakoudis, P; Billi, H; Tantanassis, T; Kalachanis, I; Garipidou, B; Sinakos, Z; Mantalenakis, S

    1995-10-01

    Clinical data from eight pregnant women with idiopathic thrombocytopenic purpura (ITP) were retrospectively analyses. The mean age of the women was 28.2 years. Five women underwent splenectomy during childhood. The lowest maternal platelet count observed ranged from 8000 to 88000/mm3. Genital bleeding occurred in only one case. Treatment was based on administration of corticosteroids with or without human-pooled immunoglobulins. Caesarian section was performed in all cases. Six newborns were healthy and had a successful subsequent course. Two infants died, one in utero because of abruptio placentae and the other one 1 month post partum because of a cerebral haematoma. After a mean follow-up of eighteen months, thrombocytopenia is still present in two women, despite the continuous treatment. In conclusion, ITP rather rarely coincides with pregnancy. Treatment is usually successful for the mother but the risk for the fetus remains considerably high. PMID:8543133

  12. Management of immune thrombocytopenic purpura in pregnancy.

    PubMed

    Sukenik-Halevy, R; Ellis, M H; Fejgin, M D

    2008-03-01

    Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a low platelet count and mucocutaneous bleeding. Pregnancy does not increase the incidence of ITP nor does it exacerbate a preexisting disease. Although pregnant women with ITP may experience several maternal and fetal complications, in most cases even with a very low platelet count, there is neither maternal nor fetal morbidity or mortality. Corticosteroids are the first line of therapy in pregnant women; intravenous immune globulin is commonly used in steroid resistant patients. Other treatments such as intravenously administered anti-D (Rhogam) and splenectomy during pregnancy have been reported. Antiplatelet IgG antibodies can cross the placenta and can induce fetal thrombocytopenia. In most women there is no indication to assess fetal platelet counts during the pregnancy. The mode of delivery is determined by obstetrical considerations. PMID:18279544

  13. Management of thrombotic thrombocytopenic purpura: current perspectives

    PubMed Central

    Blombery, Piers; Scully, Marie

    2014-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy which causes significant morbidity and mortality unless promptly recognized and treated. The underlying pathogenesis of TTP is a severe deficiency in ADAMTS13 activity, a metalloprotease that cleaves ultralarge von Willebrand factor multimers. This deficiency is either autoantibody mediated (acquired TTP) or due to deleterious mutations in the gene encoding ADAMTS13 (congenital TTP). The elucidation of this disease mechanism has reinforced the rationale and place of current therapies (eg, plasma exchange) as well as providing a basis for the prospective evaluation of immunotherapy with rituximab in addition to classic immunosuppression (eg, corticosteroid) in autoantibody-mediated TTP. This review discusses the current evidence base for therapeutic interventions in acquired and congenital TTP as well as providing a practical approach to the other aspects of investigation and management for which a firm evidence base is lacking. Novel agents that are currently being evaluated in prospective trials and future directions of therapy are also discussed which are expected to make an important contribution to improving outcomes in patients with TTP. PMID:24523598

  14. How I treat refractory thrombotic thrombocytopenic purpura.

    PubMed

    Sayani, Farzana A; Abrams, Charles S

    2015-06-18

    Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) without an obvious cause, and may include fever, mild renal failure, and neurologic deficits. It is characterized by a deficiency of the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13), resulting in formation of microthrombi in the high sheer environment of the microvasculature. This causes microvascular occlusion, MAHA, and organ ischemia. Diagnosis is based on the presence of clinical symptoms, laboratory aberrations consistent with MAHA, decreased ADAMTS13 activity, and possibly presence of anti-ADAMTS13 autoantibodies. Upfront treatment of acute TTP includes plasma exchange and corticosteroids. A significant number of patients are refractory to this treatment and will require further interventions. There are limited data and consensus on the management of the refractory TTP patient. Management involves simultaneously ruling out other causes of thrombocytopenia and MAHA, while also considering other treatments. In this article, we describe our management of the patient with refractory TTP, and discuss use of rituximab, increased plasma exchange, splenectomy, and immunosuppressive options, including cyclophosphamide, vincristine, and cyclosporine. We also review recent evidence for the potential roles of bortezomib and N-acetylcysteine, and explore new therapeutic approaches, including recombinant ADAMTS13 and anti-VWF therapy. PMID:25784681

  15. Treatment of immune thrombocytopenic purpura in adults.

    PubMed

    Bussel, James

    2006-07-01

    Idiopathic thrombocytopenic purpura (ITP) is a hematologic disorder characterized by the destruction of antibody-coated platelets in the reticuloendothelial system. Whereas 70% to 80% of children experience the acute form of the disease and recover within a few weeks or months after diagnosis, most adults have persistent disease and will require therapy. Principles of management are largely predicated on the extent of thrombocytopenia and symptoms of disease. Minimizing the toxicity associated with treatment while achieving hemostatic platelet counts are essential goals of treatment. Although there are numerous therapeutic options, neither consensus among experts nor clear algorithms to treat this complex disease exist. This article will review appropriate treatment options available for adult patients with ITP prior to splenectomy, at splenectomy, and following splenectomy. In addition to conventional agents such as corticosteroids and intravenous immune globulin (IVIg), the role of newer therapies with diverse mechanisms of action, such as rituximab, anti-D, and thrombopoietin (TPO)-like agents, will be highlighted. When used as either monotherapy or in combination with conventional therapeutics, these treatments may offer a more tolerable side effect profile and improved clinical benefit compared to existing drugs. PMID:16815346

  16. Cytomegalovirus can make immune thrombocytopenic purpura refractory.

    PubMed

    DiMaggio, Dina; Anderson, Alan; Bussel, James B

    2009-06-01

    Immune thrombocytopenic purpura (ITP) is characterized by decreased platelet numbers secondary to platelet destruction and reduced platelet production. Even if the ITP persists, it typically responds to 'ITP-specific' therapies, such as intravenous immunoglobulin, steroids, intravenous anti-D, and splenectomy. Several reports, including our previous study, have implicated cytomegalovirus (CMV) in the pathogenesis of infrequent cases of ITP that were not severe in nature. A recent study from China suggested that CMV is the aetiology of some cases of acute ITP of childhood and may require different treatment. We report two adult and two paediatric patients with refractory, severe, symptomatic thrombocytopenia, who were diagnosed with ITP and found to have active CMV infection. Their presentations included fever, transaminitis, neutropenia, and atypical lymphocytosis, but in particular, treatment-refractory, severe ITP. Treatment with steroids appeared to worsen the CMV-ITP. All four cases showed improvement in platelet counts within two weeks of starting ganciclovir and cytogam and tapering steroids. Based on the four patients described here, we believe that, in certain cases, CMV infection will result in symptomatic, severe, refractory ITP, which may be indistinguishable from typical ITP. Eradication of CMV with antiviral therapy improved the ITP in these cases. PMID:19438507

  17. Treatment of acquired amegakaryocytic thrombocytopenic purpura with cyclophosphamide.

    PubMed

    el Saghir, N S; Geltman, R L

    1986-07-01

    A patient with severe amegakaryocytic thrombocytopenic purpura was treated with cyclophosphamide and had an excellent response after four weeks. His condition remained in complete remission for at least five months. Acquired amegakaryocytic thrombocytopenic purpura is a rare disorder with several possible causes. An intrinsic defect at the level of the megakaryocyte colony-forming units, or a circulating autoantibody directed against these colony-forming units has been suggested. This patient's response to cyclophosphamide supports the hypothesis of an immune mechanism in some of these cases, and it is recommended that immunosuppressive therapy be further evaluated. PMID:3728540

  18. Danazol in acquired amegakaryocytic thrombocytopenic purpura: a case report.

    PubMed

    Kayser, W; Euler, H H; Schmitz, N; Gassmann, W; Löffler, H; Asbeck, F

    1985-12-01

    Acquired amegakaryocytic thrombocytopenic purpura is a rare disease. Most reported patients did not respond to any therapeutical approach. Recently we observed a striking improvement of this disorder in a female patient shortly after therapy with danazol had been initiated. This observation and its possible implication for the treatment of amegakaryocytic thrombocytopenia are reported herein. PMID:3852685

  19. Danazol in acquired amegakaryocytic thrombocytopenic purpura: A case report

    Microsoft Academic Search

    W. Kayser; H. H. Euler; N. Schmitz; W. Gassmann; H. Löffler; F. Asbeck

    1985-01-01

    Acquired amegakaryocytic thrombocytopenic purpura is a rare disease. Most reported patients did not respond to any therapeutical approach. Recently we observed a striking improvement of this disorder in a female patient shortly after therapy with danazol had been initiated. This observation and its possible implication for the treatment of amegakaryocytic thrombocytopenia are reported herein.

  20. Pulmonary Endarterectomy in a Patient with Immune Thrombocytopenic Purpura

    PubMed Central

    Y?ld?zeli, Bedrettin; Yanarta?, Mehmed; Keskin, Sibel; Atagündüz, I??k; Alt?nay, Ece

    2015-01-01

    Immune thrombocytopenic purpura (ITP) patients are at high risk for bleeding complications regarding surgeries involving cardiopulmonary bypass. We report an ITP patient with chronic thromboembolic pulmonary hypertension who underwent uncomplicated pulmonary endarterectomy with receiving postoperative intravenous immunoglobulin (IVIG) therapy. The positive outcome of this case may suggest that pulmonary endarterectomy surgery is performed safely for ITP patients. PMID:26090264

  1. Laparoscopic versus open splenectomy for immune thrombocytopenic purpura

    Microsoft Academic Search

    Rubén R Lozano-Salazar; Miguel F Herrera; Florencia Vargas-Vorácková; Xavier López-Karpovitch

    1998-01-01

    Background: Laparoscopic splenectomy (LS) has been proposed as a substitute to open splenectomy (OS) in the treatment of immune thrombocytopenic purpura (ITP). The aim of this study was to compare two cohorts of patients with ITP who underwent OS or LS.Patients and Methods: From February 1990 to January 1997, 27 patients underwent OS and 22 LS. Perioperative characteristics, outcomes, and

  2. Acquired Amegakaryocytic Thrombocytopenic Purpura Associated with Immunoglobulin Deficiency

    Microsoft Academic Search

    Montserrat Rovira; Evarist Feliu; Lourdes Florensa; Soledad Woessner; Dolors Tassies; Emili Montserrat; Joan Llouis Vives-Corrons; Ciril Rozman

    1991-01-01

    Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a haematological disorder characterized by severe thrombocytopenia due to an immunologically induced absence of megakaryocytes in an otherwise normal-appearing bone marrow. A 57-year-old male with a 6-month history of rectal and cutaneous bleeding is reported. Platelet count was 10 × 109\\/l, while other haematological values were within the normal range, except for the presence

  3. Helicobacter pylori and Immune Thrombocytopenic Purpura: Unsolved Questions and Controversies

    Microsoft Academic Search

    Masataka Kuwana; Yasuo Ikeda

    2006-01-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. Recent accumulating\\u000a evidence indicates that eradication of Helicobacter pylori (H pylori) is effective in increasing platelet count in nearly half of ITP patients infected with this bacterium. The H pylori eradication therapy for adult ITP is becoming very popular in Japan and is now chosen as an initial

  4. Chronic autoimmune thrombocytopenic purpura. A 3-year study.

    PubMed

    Fotos, P G; Graham, W L; Bowers, D C; Perfetto, S P

    1983-06-01

    Idiopathic (autoimmune) thrombocytopenic purpura (ATP) is accepted to be a disorder resulting from accelerated platelet destruction attributed to an autoimmune process. The patient whose case is presented in this article was first seen by a dentist. The oral findings have been documented as the case was followed for 3 years through acute exacerbations, pregnancy, and delivery of an infant with thrombocytopenia. The patient was managed with intermittent steroid therapy and splenectomy. PMID:6576288

  5. Sea-Blue Histiocytes in Idiopathic Thrombocytopenic Purpura

    Microsoft Academic Search

    M. I. Quadri; S. Majumdar; Y. N. Mehra; G. Garewal; K. C. Das

    1980-01-01

    Sea-blue histiocytes are described in the bone marrow of a 15-year-old male patient suffering from idiopathic thrombocytopenic purpura. Cytochemically the storage material in these cells appeared to be glycophospholipid. Lipid analysis of blood leucocytes and nucleated cells of bone marrow showed a significant increase in the phospholipids, triglycerides and cholesterol as compared to age-matched controls. Serum lipid analysis showed a

  6. Thrombotic thrombocytopenic purpura in the first trimester of pregnancy

    PubMed Central

    Sikka, Pooja; Chopra, Seema; Aggarwal, Neelam; Suri, Vanita; Chandrasekaran, Abi

    2013-01-01

    Thrombotic thrombocytopenic purpura (TTP) occurs more commonly in women and so can be associated with pregnancy. The time during pregnancy with greatest risk for development of TTP is near term and during the post partum period. TTP occurring in early trimester is uncommon and is also associated with great maternal and fetal mortality. We report a successful outcome of pregnancy in a woman with TTP in early first trimester who was treated with therapeutic plasma exchange. PMID:23559773

  7. Genetics Home Reference: Thrombotic thrombocytopenic purpura

    MedlinePLUS

    ... purpura also results from a reduction in ADAMTS13 enzyme activity; however, people with the acquired form do not ... activity of the enzyme. A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. ...

  8. Immune Thrombocytopenic Purpura Presenting as Unprovoked Gingival Hemorrhage: a Case Report

    PubMed Central

    Bal, Mehmet V; Koyuncuoglu, Cenker Z; Saygun, I??l

    2014-01-01

    Immune thrombocytopenic purpura is an autoimmune disease characterized by auto-antibody induced platelet destruction and reduced platelet production, leading to low blood platelet count. In this case report, the clinical diagnose of a patient with immune thrombocytopenic purpura and spontaneous gingival hemorrhage by a dentist is presented. The patient did not have any systemic disease that would cause any spontaneous hemorrhage. The patient was referred to a hematologist urgently and her thrombocyte number was found to be 2000/?L. Other test results were in normal range and immune thrombocytopenic purpura diagnose was verified. Then hematological treatment was performed and patient’s health improved without further problems. Hematologic diseases like immune thrombocytopenic purpura, in some cases may appear firstly in the oral cavity and dentists must be conscious of unexplained gingival hemorrhage. In addition, the dental treatment of immune thrombocytopenic purpura patients must be planned with a hematologist. PMID:25317211

  9. Autoimmune Thrombocytopenic Purpura and Helicobacter pylori Infection

    Microsoft Academic Search

    Marc Michel; Mehdi Khellaf; Lionel Desforges; Ketty Lee; Annette Schaeffer; Bertrand Godeau; Philippe Bierling

    Background: The mechanisms triggering the produc- tion of platelet autoantibodies in autoimmune thrombo- cytopenic purpura (AITP) are poorly understood. Re- cently, marked improvements in platelet counts have been reported in patients with AITP and concurrent Helico- bacter pylori infection after eradication of H pylori by a standard antibiotic regimen. We looked for an associa- tion between H pylori infection and

  10. [Acquired amegakaryocytic thrombocytopenic purpura treated with intravenous immunoglobulins].

    PubMed

    El Omri, H; Skouri, H; Kraiem, I; Latiri, A; Khelif, A; Korbi, S; Ennabli, S

    2000-05-01

    Acquired amegakaryocytic thrombocytopenic purpura is a rare disorder characterized by severe thrombocytopenia due to the absence of bone marrow megakaryocytes. The pathogenic mechanisms of this disorder have not well defined; consequently, several empirical therapies are used. We reported the case of a 38-year-old mean who was hospitalized for serious bleeding syndrome. The platelet count was 10 yen10(9)/L. The bone marrow aspirate and biopsy showed the absence of megakaryocytes but otherwise normal granulocyte and erythroid precursors. No definable etiology has been found. After the unsuccessful use of prednisone, intravenous immunoglobulin therapy was started and resulted in favorable reponse. PMID:10896976

  11. Monoclonal antibodies in the treatment of immune thrombocytopenic purpura (ITP).

    PubMed

    Gómez-Almaguer, David

    2012-04-01

    Immune thrombocytopenic purpura is characterized by antibody-mediated destruction of platelets and suboptimal platelet production. Initially the treatment of ITP includes corticosteroids, IgG-anti-D, and intravenous immunoglobulins. Splenectomy and monoclonal antibodies are usually considered for refractory and chronic ITP patients. There are new data suggesting that early administration of rituximab is important, and this antibody has been used as first-line therapy in adults. In this concise review the role of rituximab and other monoclonal antibodies is analyzed. These agents have the capability of sparing splenectomy and possibly curing the disease in some patients. PMID:22507772

  12. Severe immune thrombocytopenic purpura treated with plasma exchange.

    PubMed

    Sigdel, M R; Shah, D S; Kafle, M P; Raut, K B

    2012-01-01

    Immune thrombocytopenic purpura (ITP) is a hematological disorder characterized by immunologically mediated destruction of platelets and absence of other causes of thrombocytopenia. Treatment is required when the low platelet count entails risk of serious bleeding. Steroid is the first line of management. Acute refractory ITP with very low platelet count is variably treated with high dose steroid, intravenous immunoglobulin (IVIg), anti D or emergency splenectomy. Here, we present a case of steroid resistant ITP with severe thrombocytopenia treated with plasma exchange and low dose IVIg who responded dramatically to the therapy with maintained platelet count till one month from the institution of therapy. PMID:22971870

  13. Malignant Hypertension and Thrombotic Thrombocytopenic Purpura: False Friends

    PubMed Central

    Abdalla, Hossam; Alfishawy, Mostafa; Babigumira, Michael; Bashir, Tayyaba

    2015-01-01

    Patient: Male, 63 Final Diagnosis: Thrombotic thrombocyopenic purpura Symptoms: — Medication: — Clinical Procedure: Plasmapharesis Specialty: Hematology Objective: Challenging differential diagnosis Background: Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder resulting in hemolysis of red blood cells, consumption of platelets, and occlusion of microvasculature. Malignant hypertension is the clinical syndrome of severe elevations in blood pressure and funduscopic hypertensive retinopathy, including bilateral flame-shaped hemorrhage and papilledema. Case Report: We describe the case of a 63-year-old man who presented with features of TTP and malignant hypertension treated with plasma exchange and developing end-stage renal disease. Conclusions: Given the diagnostic uncertainty at presentation, clinicians should quickly intervene to control hypertension and institute plasma exchange as needed. PMID:26083445

  14. The Role of Autoreactive T-cells in the Pathogenesis of Idiopathic Thrombocytopenic Purpura

    Microsoft Academic Search

    Masataka Kuwana; Yasuo Ikeda

    2005-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease mediated by antiplatelet autoantibodies.The major target\\u000a of these autoantibodies is a platelet membrane glycoprotein, GPIIb-IIIa, which is a receptor for fibrinogen and other ligands.\\u000a We recently identified CD4+ T-cells autoreactive to GPIIb-IIIa in ITP patients.These T-cells are considered pathogenic because\\u000a they help B-cells produce antibodies that bind to normal platelet surfaces. GPIIb-IIIa-reactive

  15. Initial management of adults with idiopathic (immune) thrombocytopenic purpura.

    PubMed

    George, J N

    2002-03-01

    Since idiopathic (immune) thrombocytopenic purpura (ITP) in adults is usually a chronic condition with few spontaneous remissions, the goal of treatment is not cure, but to maintain a hemostatically safe platelet level. The indication for treatment should be based not merely on platelet counts, but also clinical indices of bleeding. Although most patients show good initial response to prednisone, the side effects of steroids limit this treatment. Currently, long-term management usually involves splenectomy. Since splenectomy has surgical risks and may also predispose the patient to sepsis, a clinical trial using anti-D (WinRho-SDR) has been performed to determine whether this treatment can safely delay or avoid the need for surgery. The use of WinRho may also reveal the occurrence of spontaneous remissions, a previously unrecognized subgroup of adults with chronic ITP. PMID:11913992

  16. ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura.

    PubMed

    Zheng, X Long

    2015-01-01

    Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (>20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia. PMID:25587650

  17. Acquired amegakaryocytic thrombocytopenic purpura associated with immunoglobulin deficiency.

    PubMed

    Rovira, M; Feliu, E; Florensa, L; Woessner, S; Tassies, D; Montserrat, E; Vives-Corrons, J L; Rozman, C

    1991-01-01

    Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a haematological disorder characterized by severe thrombocytopenia due to an immunologically induced absence of megakaryocytes in an otherwise normal-appearing bone marrow. A 57-year-old male with a 6-month history of rectal and cutaneous bleeding is reported. Platelet count was 10 X 10(9)/l, while other haematological values were within the normal range, except for the presence of hypogammaglobulinaemia with decreased IgA and IgG. Both platelet median volume and half-life span were normal, and antiplatelet IgG determinations were negative. Bone marrow aspiration and biopsy showed no megakaryocytes, with a normal appearance of erythroblastic and granulopoietic series. An in vitro culture for megakaryocytic progenitor cells did not show any growth of megakaryocyte colonies. No inhibitory effect on the growth of normal marrow megakaryocytic colonies was observed when serum and lymphocytes of the patient were added. Following 4 weeks of prednisone therapy, the platelet count rose to 127 X 10(9)/l and the bone marrow aspirate showed some megakaryocytes. The possible pathogenetic mechanisms of this entity are discussed. PMID:2011928

  18. Acquired amegakaryocytic thrombocytopenic purpura with a Philadelphia chromosome.

    PubMed

    Xue, Y; Zhang, R; Guo, Y; Gu, J; Lin, B

    1993-08-01

    A 30-year-old Chinese man with acquired amegakaryocytic thrombocytopenic purpura (AATP) and a Ph chromosome is reported. At presentation, he had severe thrombocytopenia resulting in epistaxis, gingival bleeding, and ecchymoses, while other hematologic values were within the normal range. Bone marrow aspiration showed no megakaryocytes, with a normal appearance of erythroblastic and granulopoietic series. He failed to respond to prednisone treatment, and underwent a progress from isolated thrombocytopenia to full pancytopenia. At last he died of spontaneous intracranial hemorrhage. An in vitro culture for granulocyte-macrophage precursors showed very few colonies. Karyotypic analysis revealed a standard Ph chromosome translocation, t(9;22)(q34;q11), in the majority of bone marrow cells. Southern blot analysis using a 3' bcr-HE probe didn't detect a rearrangement within the bcr DNA sequence. This patient, in fact, was a myelodysplastic disorder, initially presenting as AATP. The diagnosis of chronic myelogenous leukemia was excluded on the basis of clinical and hematologic findings. The heterogeneity of Ph chromosome in myelodysplastic syndrome is discussed. PMID:8374901

  19. Gemcitabine-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

    PubMed

    Held-Warmkessel, Jeanne

    2014-09-01

    A patient being treated for metastatic adenocarcinoma of the pancreas presents to the clinic for a routine appointment. A complete blood count reveals hemoglobin of 6.5 g/dl and a platelet count of 30,000 K/mm3 thought to be from the last of many doses of gemcitabine. On assessment, the only complaint was fatigue with no evidence of bleeding or other abnormal physical findings other than pallor. Past medical history includes hypertension managed with three antihypertensive agents. Additional laboratory tests reveal elevated blood urea nitrogen (69 mg/dl), creatinine (2.76 mg/dl), and lactic dehydrogenase (LDH), was well as indirect bilirubin (2.1 mg/dl). The patient is admitted and transfused with packed red blood cells (pRBCs). The next day, the platelet count drops to 9,000 K/mm3 and the hemoglobin increases, appropriately, to 8.9 g/dl. Urinalysis is positive for hemoglobin (+ 3). The peripheral blood smear is positive for schistocytes (fragmented RBCs). A pheresis catheter is placed after the patient was evaluated by a hematologist and a nephrologist. A presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) with hemolytic uremic syndrome (HUS) was made. PMID:25158661

  20. Treatment options for chronic idiopathic (immune) thrombocytopenic purpura.

    PubMed

    George, J N

    2000-01-01

    The goal of treatment for idiopathic (immune) thrombocytopenic purpura (ITP) is to prevent serious bleeding. Traditionally, corticosteroids have been used as first-line therapy followed by splenectomy. Experience with splenectomy over 60 years shows that approximately two thirds of patients achieve normal platelet counts during the initial observation, but that thrombocytopenia often recurs with longer follow-up. We know that long-term use of corticosteroids can lead to significant morbidities; there is no consensus regarding the appropriate timing or indications for splenectomy. To address the Issue of appropriate use of splenectomy, we designed a multicenter clinical trial that will randomize patients to either standard care, involving prednisone followed by splenectomy, or to a novel regimen of limited prednisone treatment followed by WinRho SDF (Nabi, Boca Raton, FL) (anti-D) therapy to maintain the platelet count in a safe range for 1 year. Anti-D can be administered easily in an outpatient setting with few side effects and can provide predictable, transient increases in platelet count. The hypothesis is that prolonged maintenance therapy with a nontoxic regimen may increase the percentage of patients who will experience a spontaneous remission from thrombocytopenia, thereby avoiding an invasive and permanent surgical procedure, splenectomy, and its potentially life-threatening sequelae. PMID:10676922

  1. Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias

    SciTech Connect

    Sugiura, K.; Steiner, M.; Baldini, M.G.

    1980-10-01

    Platelet-associated immunoglobulin was measured by the use of fluorescent anti-1gG antibody. The method is simple, rapid, and sensitive and provides a precise quantitive assay of bound (direct) and free (indirect) 1gG with platelet specificity. We have evaluated this test in 30 normal volunteers and in 50 patients with immune and nonimmune, treated and untreated thrombocytopenias. All patients with immune thrombocytopenias (acute and chronic idiopathic thrombocytopenic purpura and systemic lupus erythematosus) having platelet counts < 100,000/..mu..l had elevated levels of platelet-bound 1gG and 86% had also positive results in the indirect assay. All patients with nonimmunological thrombocytopenias showed normal results in the direct and indirect assay of platelet-associated immunoglobulin. In patients studied repeatedly during the course of their illness, an inverse relation was found between platelet count and level of platelet-bound 1gG. Patients with systemic lupus erythematosus presented clear exceptions to this rule. Investigations of the absorbability of platelet autoantibodies and alloantibodies showed that this assay can readily differentiate between these two antibody species and can also identify specificities of alloantibodies.

  2. Recent advances in the treatment of childhood immune thrombocytopenic purpura.

    PubMed

    Tarantino, Michael

    2006-07-01

    Immune thrombocytopenic purpura (ITP), the most common bleeding disorder in childhood, is a benign condition that typically resolves within 6 months following diagnosis. While all would agree on drug treatment for children with severe hemorrhage, management strategies of the minimally symptomatic child with a very low platelet count can vary widely. The case for treatment is based primarily on the risk for the uncommon complication of intracranial hemorrhage or other serious bleeding. Numerous clinical studies clearly indicate that immune globulins (intravenous immune globulin [IVIg] or anti-D) and corticosteroid therapy (prednisone and megadose methylprednisolone) are effective in rapidly raising platelet counts. However, physicians must ultimately decide whether to use drug therapy for a patient with minimal symptoms and low platelet count or adopt an "observation-only" approach. With this background, three fundamental questions emerge when evaluating different clinical strategies and potential outcomes: (1) Which children with ITP need treatment? (2) Which pharmacologic agent best accomplishes the goals of drug treatment? (3) Can physicians better predict the outcome of treatments? PMID:16815345

  3. Rapid encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

    PubMed

    Golla, Sunitha; Horkan, Clare; Dogaru, Grigore; Teske, Thomas E; Christopher, Kenneth

    2008-01-01

    Rho (D) immune globulin intravenous (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura. Common side effects of IV RhIG include mild hemolysis, febrile reaction and headache. Significant hemolysis with renal impairment is infrequently noted. A single case of irreversible encephalopathy following IV RhIG has been reported. We report a second case of encephalopathy following an infusion of IV RhIG for treatment of idiopathic thrombocytopenic purpura. PMID:18957844

  4. A Case Associated with Comorbidities Among Cerebral Infarction, Idiopathic Thrombocytopenic Purpura, and Triple X Syndrome

    PubMed Central

    Kim, Hanjun; Hwang, Sang Sun; Uh, Young; Kim, Juwon; Yoon, Kap Jun; Lee, Ji-Yong

    2014-01-01

    A 46-year-old female presented to the emergency room due to the chief complaint of left-sided weakness. By imaging study, she was diagnosed with cerebral infarction. Thrombolytic and antiplatelet agents were not considered due to the “golden hour” for treatment having passed and a low platelet count. The peripheral blood smear, bone marrow biopsy, and aspirate findings were consistent with immune thrombocytopenic purpura. The chromosome analysis revealed the 47,XXX karyotype. To the best of our knowledge, this is the first case report associated with the comorbidities of cerebral infarction, idiopathic thrombocytopenic purpura, and triple X syndrome. PMID:25035678

  5. Antiphospholipid antibodies in adults with immune thrombocytopenic purpura.

    PubMed

    Pierrot-Deseilligny Despujol, Carole; Michel, Marc; Khellaf, Mehdi; Gouault, Michèle; Intrator, Liliane; Bierling, Philippe; Godeau, Bertrand

    2008-08-01

    To determine the clinical significance of antiphospholipid antibodies (aPL) in patients with immune thrombocytopenic purpura (ITP), anticardiolipin (aCL) (IgG and IgM) and lupus anticoagulant (LA) were sought at diagnosis in 215 ITP adults with platelets <50 x 10(9)/l. aPL (aCL and/or LA) were detected in 55 patients (26%): aCL alone in 39 (18%), aCL and LA in 15 (7%) and LA alone in one (0.5%). LA was significantly associated with high IgG-aCL levels (P = 0.001). Among age, sex, initial platelet count, bleeding score, acute or chronic ITP outcome, only younger age was significantly associated with LA-positivity (mean age 29 +/- 14 years vs. 45 +/- 20 years, P = 0.002). After a median follow-up of 31 months, 14/215 (7%) patients developed thrombosis (four arterial, 10 venous and/or pulmonary embolism); four of them (29%) had high aCL levels and LA. Multivariate analysis significantly associated thrombosis events only with age [hazard ratio (HR) = 1.6; 95% confidence interval (CI): 1.2-2.4], LA (HR: 9.9; 95% CI: 2.3-43.4) or high IgG-aCL level (HR: 7.5; 95% CI; 1.8-31.5). Although the thrombosis rate was low, the significant associations between thrombosis and LA or high aCL level suggest that aPL should be tested at ITP diagnosis. PMID:18510681

  6. Successful treatment with cyclosporin A in a child with acquired pure amegakaryocytic thrombocytopenic purpura.

    PubMed

    Peng, C T; Kao, L Y; Tsai, C H

    1994-11-01

    Idiopathic acquired pure amegakaryocytic thrombocytopenic purpura (APATP) in young patients (non-neonates) is a rare disorder with a variable clinical course. Cure is unusual. A 13.5-year-old boy with idiopathic APATP was treated with cyclosporin A. Apparently effective, the treatment resulted in the reappearance of marrow megakaryocytes and normalization of platelet count. PMID:7841744

  7. Acquired amegakaryocytic thrombocytopenic purpura: Review of a not very well-defined disorder

    Microsoft Academic Search

    Antonio G. Tristano

    2005-01-01

    Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a hematological disorder characterized by severe thrombocytopenia, probably due to an immunologically induced absence of megakaryocytes with a marked decrease or total absence of megakaryocytes in the bone marrow. AATP may be differentiated from other causes of peripheral destruction of platelets, such as immune thrombocytopenia (ITP). Currently, there are no standard treatments for AATP.

  8. A case of lupus cystitis with a history of idiopathic thrombocytopenic purpura

    Microsoft Academic Search

    Miwa Haranaka; Midori Kumagi; Ikuko Hino; Kaori Watanabe; Hiroshi Tatsukawa; Koji Ishii; Hironobu Yoshimatsu

    2004-01-01

    A 36-year-old Japanese woman who had been diagnosed as having systemic lupus erythematosus (SLE) at the age of 34 began to complain of severe bowel symptoms and developed severe hydroureteronephrosis. She had a history of idiopathic thrombocytopenic purpura. Biopsy specimens from her bladder showed interstitial cystitis. She was diagnosed as having lupus cystitis, and treated with intravenous methylprednisolone pulse therapy

  9. Idiopathic thrombocytopenic purpura of childhood: A problem-oriented review of the management

    Microsoft Academic Search

    Thomas Kühne

    2003-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an often, but not always, self-limited bleeding disorder of childhood of unknown etiology. Duration of more than 6 months defines the chronic form and this occurs in approximately 20% of children and is the common form of the disorder in adults. At initial diagnosis, neither the individual bleeding risk nor the form of the disease,

  10. Platelet and immune responses to oral cyclic dexamethasone therapy in childhood chronic immune thrombocytopenic purpura

    Microsoft Academic Search

    Thomas Kühne; John Freedman; John W. Semple; John Doyle; Sheila Butchart; Victor S. Blanchette

    1997-01-01

    Objective: To examine the effectiveness of cyclic oral high-dose (HD) dexamethasone therapy in pediatric patients with chronic immune thrombocytopenic purpura (ITP), which has been reported to cause complete remission in adults with chronic ITP.Study design: Eleven children with primary chronic ITP, with a median disease duration of 28 months (range, 6 to 120 months), were treated with cycles of HD

  11. Two cases of thrombohaemolytic thrombocytopenic purpura associated with changes in red cell morphology

    Microsoft Academic Search

    P. McCormack; D. J. OBrien; R. A. M. Oliver

    1963-01-01

    Two adult cases of thrombohaemolytic thrombocytopenic purpura are described. Both showed striking morphological changes in the red cells with increased saline osmotic fragility, in addition to thrombocytopenia and generalized hyaline thrombi affecting small blood vessels. These changes support the hypothesis that this is a triple auto-immune disorder affecting red cells, platelets, and small blood vessels.

  12. Successful management of thrombotic thrombocytopenic purpura in a Jehovah's Witness without plasma exchange.

    PubMed

    Chai, Wanxing; Chaudhry, Abrar; Rabinowitz, Arthur P

    2015-02-01

    Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency characterized by microangiopathic hemolytic anemia and thrombocytopenia. Plasma exchange is the standard treatment. Treating TTP without plasma exchange is a challenge. Due to religious beliefs, Jehovah's Witnesses do not accept transfusions of blood products. We report a case of successful treatment of TTP in a Jehovah's Witness using plasma exchange with albumin replacement. PMID:24782109

  13. Acquired amegakaryocytic thrombocytopenic purpura: a syndrome of diverse etiologies.

    PubMed

    Hoffman, R; Bruno, E; Elwell, J; Mazur, E; Gewirtz, A M; Dekker, P; Denes, A E

    1982-11-01

    The possible pathogenetic mechanisms responsible for the production of acquired amegakaryocytic thrombocytopenic purpura (AATP) were investigated in a group of patients with this disorder. Absence of megakaryocytes and small platelet glycoprotein-bearing mononuclear cells, as determined by immunochemical staining of patient marrows with an antisera to platelet glycoproteins, suggested that the defect in AATP occurs in an early progenitor cell of the megakaryocytic lineage. Using an in vitro clonal assay system for negakaryocytic progenitor cells or megakaryocyte colony-forming units (CFU-M), the proliferative capacity of AATP marrow cells was then assessed. Bone marrow cells from three of four patients formed virtually no megakaryocyte colonies, suggesting that in these individuals the AATP was due to an intrinsic defect in the CFU-M. Bone marrow cells from an additional patient, however, formed 12% of the normal numbers of colonies, providing evidence for at least partial integrity of the CFU-M compartment in this patient. Serum specimens from all six patients were screened for their capacity to alter in vitro megakaryocyte colony formation. Five of six sera enhanced colony formation in a stepwise fashion, demonstrating appropriately elevated levels of megakaryocyte colony-stimulating activity. The serum of the patient with partial integrity of the CFU-M compartment, however, stimulated colony formation only at low concentrations. At higher concentrations, this patient's serum actually inhibited the number of colonies cloned, suggesting the presence of a humoral inhibitor to CFU-M. Serum samples from all patients were further screened for such humoral inhibitors of megakaryocyte colony formation using a cytotoxicity assay. The patient whose serum was inhibitory to CFU-M at high concentrations was indeed found to have a complement-dependent serum IgG inhibitor that was cytotoxic to allogeneic and autologous marrow CFU-M but did not alter erythroid colony formation. These-studies suggest that AATP can be due to at least two mechanisms: either an intrinsic effect at the level of the CFU-M or a circulating cytotoxic autoantibody directed against the CFU-M. PMID:6982086

  14. HLA and HPA typing in idiopathic thrombocytopenic purpura patients treated with Kami-kihi-to.

    PubMed

    Matsuzaki, T; Nomura, S; Yamaoka, M; Ozaki, Y; Yoshimura, C; Xie, G L; Katsura, K; Kagawa, H; Ishida, T; Fukuhara, S

    1998-01-01

    We performed human leukocyte antigen (HLA) and human platelet antigen (HPA) in patients with Kami-kihi-to-responsive idiopathic thrombocytopenic purpura. The HLA-A2, A61 and Cw1 were significantly increased in responders compared with nonresponders, as were HLA DRB1 *0901, DRB1 *1502, and DPB1 *0501. In contrast, HLA DPB1 *0201 and DPB1 *0901 were significantly decreased in responders. The a/b genotype of HPA-2 and a/a genotype of HPA-3 were markedly increased in nonresponders, and anti-GPIb antibody was also increased. These results suggest that HLA, HPA, and anti-GP antibody studies may predict the response of idiopathic thrombocytopenic purpura to Kami-kihi-to. PMID:9799971

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

    PubMed

    Liebman, Howard A

    2009-01-01

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

  16. Danazol therapy in cyclic acquired amegakaryocytic thrombocytopenic purpura: a case report.

    PubMed

    Kashyap, R; Choudhry, V P; Pati, H P

    1999-03-01

    Cyclic acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disorder characterized by periodic fluctuations in the platelet counts due to a defect in the platelet production. We describe a 42-year-old female with cyclic AATP, in whom the cyclic fluctuations in the platelet counts ceased with danazol therapy. The pathogenesis of the disease and the possible mechanisms of danazol action have been reviewed. PMID:10072115

  17. Health-related quality of life outcomes for patients with immune thrombocytopenic purpura

    Microsoft Academic Search

    Robert J. Klaassen; Nancy L. Young

    2010-01-01

    Immune thrombocytopenic purpura (ITP) is a rare disease with infrequent serious bleeding making clinical trials difficult.\\u000a One solution to this problem is to use alternative outcome measures such as health-related quality of life (HRQL). This review\\u000a describes the various HRQL tools available to researchers including measures that are generic (applicable to many different\\u000a disease types) and disease-specific measures developed explicitly

  18. Immune Thrombocytopenic Purpura and Percutaneous Umbilical Blood Sampling: An Open Question

    Microsoft Academic Search

    Sara De Carolis; Giuseppe Noia; Marco De Santis; Carmen Trivellini; Carmen Mastromarino; Maria Pia De Carolis; Sergio Ferrazzani; Alessandro Caruso

    1993-01-01

    We performed a retrospective study of 26 pregnancies with chronic immune thrombocytopenic purpura (ITP) or incidental ITP. Thirteen pregnancies were followed without the use of percutaneous umbilical blood sampling (PUBS) and 13 were followed sampling PUBS at 36–40 weeks of gestation. The overall prevalence of neonatal thrombocytopenia was 27%: 50% in chronic ITP, 12.5% in incidental ITP. Symptomatic thrombocytopenia occurred

  19. Rapid irreversible encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

    PubMed

    Christopher, Kenneth; Horkan, Clare; Barb, Ilie T; Arbelaez, Christian; Hodgdon, Travis A; Yodice, Paul C

    2004-11-01

    Intravenous Rho (D) immune globulin (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura (ITP). Common side effects of IV RhIG include mild hemolysis, febrile reaction, and headache. Significant hemolysis with renal impairment following IV RhIG has been reported. We report a case of irreversible encephalopathy 48 hr following an infusion of IV RhIG for treatment of ITP. PMID:15495245

  20. A case of autoimmune pancreatitis with metachronous appearance of idiopathic thrombocytopenic purpura

    Microsoft Academic Search

    Hiroaki Sawai; Hiroyuki Matsubayashi; Masaki Tanaka; Yuichiro Yamaguchi; Hiroyuki Ono

    2010-01-01

    Autoimmune pancreatitis (AIP) is often associated with systemic disorders, but a case accompanied with idiopathic thrombocytopenic\\u000a purpura (ITP) is very rare. A 67-year-old man was referred to our institution with complaints of abdominal pain and jaundice.\\u000a Multiple images showed diffuse enlargement of the pancreas, narrowing of the main pancreatic duct, stenosis of the lower common\\u000a bile duct and thickness of

  1. The indirect platelet suspension immunofluorescence test in the detection of platelet antibodies in idiopathic thrombocytopenic purpura.

    PubMed

    Singhvi, A; Sudersanam, A; Rajaiah, M; Khanduri, U

    1991-10-01

    Among the various techniques developed for the detection of platelet antibodies, the platelet suspension immunofluorescence test has been reported to be simple, sensitive and reproducible, and therefore more clinically useful than other techniques available. An initial evaluation of the test was carried out for the detection of platelet autoantibodies in ten cases of idiopathic thrombocytopenic purpura. The indirect PSIFT was found to be positive in 60%. The technical aspects of the test and the problems encountered are discussed. PMID:1818026

  2. Cerebral venous thrombosis after immune thrombocytopenic purpura and anti-D immune globulin therapy.

    PubMed

    Kayyali, Husam R; Abdelmoity, Ahmed T; Morriss, M Craig; Graf, William D

    2008-03-01

    Cerebral venous thrombosis has multiple etiologies and a wide variety of clinical manifestations. This article reports on a young girl who developed cerebral venous thrombosis after intravenous anti-D immune globulin therapy for immune thrombocytopenic purpura. In this case, venous infarction was manifested by an unusual pattern of restricted diffusion limited to the corpus callosum. The cause of cerebral venous thrombosis in this patient may be related to both immune thrombocytopenia and immunoglobulin therapy. PMID:18184936

  3. Upshaw-Schulman Syndrome Revisited: A Concept of Congenital Thrombotic Thrombocytopenic Purpura

    Microsoft Academic Search

    S. Kinoshita; A. Yoshioka; Y. D. Park; H. Ishizashi; M. Konno; M. Funato; T. Matsui; K. Titani; H. Yagi; M. Matsumoto; Y. Fujimura

    2001-01-01

    Upshaw-Schulman syndrome (USS) is a congenital bleeding disorder characterized by repeated episodes of thrombocytopenia and\\u000a microangiopathic hemolytic anemia that respond to infusions of fresh frozen plasma. Inheritance of USS has been thought to\\u000a be autosomal recessive, because 2 siblings in the same family are often affected but their parents are asymptomatic. Recently,\\u000a chronic relapsing thrombotic thrombocytopenic purpura (CR-TTP), reported almost

  4. Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators.

    PubMed

    Pourrat, O; Coudroy, R; Pierre, F

    2015-06-01

    Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe consequences for maternal health, and this can be fatal when thrombotic thrombocytopenic purpura is misdiagnosed as severe HELLP syndrome. The aim of this paper is to propose relevant markers to differentiate pre-eclampsia complicated by severe HELLP syndrome from its imitators, even in the worrying situation of apparently indistinguishable conditions, and thereby assist clinical decision-making regarding whether or not to commence plasma exchange. Relevant identifiers to establish the most accurate diagnosis include the frequency of each disease and anamnestic data. Frank hemolysis, need for dialysis, neurological involvement and absence of disseminated intravascular coagulation are indicative of thrombotic microangiopathy. The definitive marker for thrombotic thrombocytopenic purpura is undetectable ADAMTS 13 activity. PMID:25879992

  5. Persistence of circulating ADAMTS13-specific immune complexes in patients with acquired thrombotic thrombocytopenic purpura

    PubMed Central

    Ferrari, Silvia; Palavra, Kristina; Gruber, Bernadette; Kremer Hovinga, Johanna A.; Knöbl, Paul; Caron, Claudine; Cromwell, Caroline; Aledort, Louis; Plaimauer, Barbara; Turecek, Peter L.; Rottensteiner, Hanspeter; Scheiflinger, Friedrich

    2014-01-01

    Anti-ADAMTS13 autoantibodies are the main cause of acquired thrombotic thrombocytopenic purpura. Binding of these antibodies to ADAMTS13 eventually results in the formation of antigen-antibody immune complexes. Circulating ADAMTS13-specific immune complexes have been described in patients with acquired thrombotic thrombocytopenic purpura, although the prevalence and persistence of these immune complexes over time have hitherto remained elusive. Here, we analyzed a large cohort of patients with acquired thrombotic thrombocytopenic purpura for the presence of free and complexed anti-ADAMTS13 antibodies. In the acute phase (n=68), 100% of patients had free IgG antibodies and 97% had ADAMTS13-specific immune complexes. In remission (n=28), 75% of patients had free antibodies (mainly IgG) and 93% had ADAMTS13-specific immune complexes. Free antibodies were mainly of subclasses IgG1 and IgG4, whereas IgG4 was by far the most prevalent in ADAMTS13-specific immune complexes. Comparison of ADAMTS13 inhibitor and anti-ADAMTS13 IgG (total and subclasses) antibody titers in acute phase and in remission samples showed a statistically significant decrease in all parameters in remission. Although non-significant, a trend towards reduced or undetectable titers in remission was also observed for ADAMTS13-specific immune complexes of subclasses IgG1, IgG2 and IgG3. No such trend was discernible for IgG4; IgG4 immune complexes persisted over years, even in patients who had been treated with rituximab and who showed no features suggesting relapse. PMID:24241492

  6. A Postoperative Thrombotic Thrombocytopenic Purpura in a Cardiac Surgery Patient: A Case Report

    PubMed Central

    Choi, Eun Jin

    2013-01-01

    Although thrombotic thrombocytopenic purpura (TTP) is a rare disease, when it develops in a post-cardiac surgery patient, it may have a fatal outcome. Since the frequency of early-onset thrombocytopenia in post-cardiac surgery patients is high, platelet concentrates are commonly transfused during postoperative management. However, when TTP is the likely diagnosis, platelet transfusion is not recommended. We experienced a postoperative TTP in a cardiac surgery patient and discovered the importance of identifying the etiology of postoperative thrombocytopenia. Here, we report the case with a brief review of the literature. PMID:23772412

  7. Acquired amegakaryocytic thrombocytopenic purpura: review of a not very well-defined disorder.

    PubMed

    Tristano, Antonio G

    2005-11-01

    Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a hematological disorder characterized by severe thrombocytopenia, probably due to an immunologically induced absence of megakaryocytes with a marked decrease or total absence of megakaryocytes in the bone marrow. AATP may be differentiated from other causes of peripheral destruction of platelets, such as immune thrombocytopenia (ITP). Currently, there are no standard treatments for AATP. However, immunosuppressive therapy including steroids, androgens, anti-thymocyte globulin (ATG), cyclophosphamide, cyclosporine A, immunoglobulins, splenectomy, and allogenic bone marrow transplantation (BMT) have all been utilized with varying degrees of success. However, a positive response in patients with AATP using steroids alone has rarely been reported in the literature. PMID:16275539

  8. Management of myocardial infarction in immune thrombocytopenic purpura with anti-phospholipid antibodies.

    PubMed

    Tabata, Rie; Tabata, Chiharu; Kita, Yoshio

    2013-01-01

    Sometimes it is difficult to distinguish anti-phospholipid syndrome (APS) from immune thrombocytopenic purpura (ITP). Here we present successful management of ITP with anti-phospholipid antibodies, complicated by acute coronary syndrome (ACS), using CT coronary angiography (CTCA). The therapy for ITP may be changed for APS if ACS was thromboembolic event. As coronary angiography is thought to be very dangerous for patients with severe thrombocytopenia, noninvasive CTCA was desirable for our patient. Since no occlusion or narrowing was observed in CTCA, she has been safely treated as ITP with immunosuppressive agents throughout the course without antiplatelet or antithrombin therapy. PMID:22733282

  9. Intravenous anti-D immunoglobulin in the treatment of resistant immune thrombocytopenic purpura in pregnancy.

    PubMed

    Sieunarine, K; Shapiro, S; Al Obaidi, M J; Girling, J

    2007-04-01

    A 35-week pregnant 38-year-old woman presented with isolated thrombocytopenia (platelet count 4 x 10(9)/l). Investigations confirmed immune thrombocytopenic purpura, and she received treatment with prednisolone and intravenous immunoglobulins with no increment in the platelet count. At 37 and 38 weeks of the pregnancy, she received two doses of WinRho (anti-D immunoglobulin) at 50 microg/kg. Five days later, with a platelet count of 46 x 10(9)/l, she had an uncomplicated normal vaginal delivery. WinRho is a useful adjunct to other first-line treatment modalities for immune thrombocytopenia in pregnancy. PMID:17309547

  10. A review of anti-D treatment of childhood idiopathic thrombocytopenic purpura.

    PubMed

    Kjaersgaard, Mimi; Hasle, Henrik

    2006-10-15

    Treatment of childhood idiopathic thrombocytopenic purpura is still an area of controversy. We reviewed the literature on anti-D treatment. Most studies used intravenous anti-D. Single doses of 50 microg/kg increased the platelet count to >or=20x10(9)/L in 70% of the children within 3 days. Intravenous anti-D seems safe in classic childhood ITP although hemolysis and occasionally renal failure may be of concern. A few studies reported intramuscularly or subcutaneously administered anti-D. Further studies on the optimal dose and route of administration of anti-D are warranted. PMID:16933265

  11. The challenges of diagnosing thrombotic thrombocytopenic purpura in the critically ill. A case report.

    PubMed

    Bindi, Maria Lucia; Mazzoni, Alessandro; Bisà, Massimo; Grazzini, Tiziana; Esposito, Massimo; Meacci, Luca; Mozzo, Roberto; Scatena, Fabrizio; Biancofiore, Gianni

    2010-10-01

    Thrombotic thrombocytopenic purpura (TTP) is associated with high mortality rates. TTP may have various and different presentations depending on the organs involved. It is now recognized to be the consequence of reduction of blood levels of the disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-13. Prompt diagnosis of TTP is paramount, because plasma exchange is the only treatment capable of improving patient's survival with a dual mechanism: removal of anti-ADAMTS-13 auto-antibodies and infusion of the active protease available in the fresh frozen plasma. We report herein on the challenges in diagnosing TTP-like complications of post-surgical facial surgery in a young male patient. PMID:20691639

  12. Changes in Follicular Helper T Cells in Idiopathic Thrombocytopenic Purpura Patients

    PubMed Central

    Xie, Jue; Cui, Dawei; Liu, Yan; Jin, Jie; Tong, Hongyan; Wang, Lei; Ruan, Guoxiang; Lu, Yun; Yuan, Huiming

    2015-01-01

    Background: Idiopathic thrombocytopenic purpura (ITP) is a primary autoimmune disease with a decreased platelet count caused by platelet destruction mediated mainly by platelet antibodies. T follicular helper (TFH) cells have demonstrated important roles in autoimmune diseases. The aim of this study is to explore the might role of TFH cells in the patients of ITP. Methods: Twenty-three ITP patients and 12 healthy controls (HC) were enrolled in this study. The frequency of circulating TFH cells in both the patients and HC was analyzed by flow cytometry. Serum interleukin (IL)-21 and IL-6 levels were measured using ELISA, and platelet antibodies were tested using a solid phase technique. Additionally, IL-21, IL-6, Bcl-6 and c-Maf mRNA expressions in peripheral blood mononuclear cells (PBMCs) were detected using real-time PCR. Results: The percentages of circulating CXCR5+ CD4+TFH cells with ICOShigh or PD-1high expression were significantly higher in the ITP patients than in the HC. Moreover, the frequencies of circulating CXCR5+ CD4+TFH cells with inducible costimulator (ICOS)high or programmed death-1 (PD-1)high expression were notably higher in ITP with platelet-antibody-positive ( ITP (+) ) patients than in ITP with platelet-antibody-negative ( ITP (-) ) patients and HC, as were the serum IL-21 and IL-6 levels (significant). Moreover, a positive correlation was found between the CXCR5+CD4+TFH cells with ICOShigh or PD-1high expression and the serum IL-21 levels of ITP (+) patients. Additionally, the mRNA expression levels of IL-21, IL-6, Bcl-6 and c-Maf were significantly increased in ITP patients, especially in ITP (+) patients. Conclusions: This study demonstrated TFH cells and effector molecules might play an important role in the pathogenesis of ITP, which are possible therapeutic targets in ITP patients. PMID:25561904

  13. Intracranial Hemorrhage in Acute and Chronic Childhood Immune Thrombocytopenic Purpura over a Ten-Year Period: An Egyptian Multicenter Study

    Microsoft Academic Search

    Mohsen Elalfy; Nancy Elbarbary; Normine Khaddah; Magy Abdelwahab; Farida El Rashidy; Hoda Hassab; Youssef Al-Tonbary

    2010-01-01

    Intracranial hemorrhage (ICH) is a rare but major cause of death in immune thrombocytopenic purpura (ITP). The authors reviewed data of 1,840 patient with ITP, from 5 pediatric hematology centers in Egypt from 1997 to 2007, to study the incidence and risk factors of ICH. Ten cases of ICH were identified with a median age at presentation of 7.5 years;

  14. The spleen and splenectomy in immune (idiopathic) thrombocytopenic purpura.

    PubMed

    Sandler, S G

    2000-01-01

    The benefits of surgical splenectomy in patients with immune (Idiopathic) thrombocytopenia purpura (ITP) probably reflect the combined effects of eliminating a source of antiplatelet antibody synthesis as well as the primary site of platelet destruction. The recent availability of intravenous Rho(D) Immune globulin (WinRho SDF; Nabi, Boca Raton, FL) presents an opportunity to extend the duration of nonsurgical (spleen-sparing) management of chronic ITP by inducing reversible Fc blockade. While new methods for laparoscopic splenectomy may offer improved surgical outcomes and reduced costs for ITP patients in the near-term, the long-term consequences of splenectomy remain to be determined. Partial splenectomy has been shown to be effective in the management of anemia in hereditary spherocytosis and elliptocytosis, while preserving vital splenic phagocytic and immune functions. The concept that cell destruction occurs in reticuloendothelial cells has been updated with recognition that the mononuclear phagocyte is neither a reticular nor an endothelial cell. Immune phagocytosis is now understood to be mediated by macrophage IgG Fc and complement receptors. A key factor for devising a strategy for selecting medical or surgical splenectomy, or postponing splenectomy, is an assessment of the relative importance of splenic immune versus phagocytic function in the pathogenesis of ITP. PMID:10676918

  15. Age old dapsone in the treatment of idiopathic thrombocytopenic purpura--a case report with review.

    PubMed

    Kundu, Ria; Sethi, Namrata; Ghose, Abhimanyu; Chaudhary, Rekha

    2013-01-01

    Idiopathic thrombocytopenic purpura (ITP) is characterized by premature platelet destruction in the reticuloendothelial system due to the presence of autoantibodies against the platelet membrane proteins. Patients who are resistant to the traditional treatment options that include the administration of steroids, IV immunoglobulin, and antirhesus D immunoglobulin and the performance of a splenectomy are diagnosed to have refractory chronic ITP. Management options in these patients are not well defined. Long-term steroids, rituximab, danazol, azathioprine, and cyclophosphamide have variable efficacy and at the same time carry significant side effects. We present the case of a patient treated effectively with dapsone, a drug that is much safer than other drugs and which can be used before resorting to splenectomy; we also include a review of the literature establishing its role in the management of ITP. PMID:21822117

  16. ADAMTS13 deficiency and thrombotic thrombocytopenic purpura associated with trimethoprim-sulfamethoxazole.

    PubMed

    Bapani, Sowjanya; Epperla, Narendranath; Kasirye, Yusuf; Mercier, Richard; Garcia-Montilla, Romel

    2013-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a hematological disease characterized by microangiopathic hemolytic anemia and thrombocytopenia. Although the link between ADAMTS13 deficiency and idiopathic TTP has been well-established, the role of trimethoprim-sulfamethoxazole (TMP-SMX) in the pathogenesis of TTP is not yet well elucidated. To the best of our knowledge, there have been only two previous reports linking this medication with the development of TTP. We present the case of a healthy woman, age 26 years, who developed TTP during TMP-SMX therapy for urinary tract infection. She was found to have ADAMTS13 deficiency with anti-ADAMTS13 antibodies. Her condition responded to discontinuation of the TMP-SMX, plasmapheresis, and rituximab therapy. We speculate that the acquired ADAMTS13 deficiency might have been triggered by the TMP-SMX therapy. PMID:23262188

  17. Managing uncontrolled postsplenectomy reactive thrombocytosis in idiopathic thrombocytopenic purpura: role of thrombocytapheresis.

    PubMed

    Das, Sudipta Sekhar; Bhattacharya, Soumya; Sen, Subrata

    2013-10-01

    Reactive thrombocytosis occurs in response to infection, trauma, or surgery. Splenectomy alone accounts for 19% of all possible causes of extreme thrombocytosis. We performed thrombocytapheresis in a young lady with chronic idiopathic thrombocytopenic purpura (ITP) who developed postsplenectomy reactive thrombocytosis. Her post splenectomy platelet count was 227 × 10(6)/ml which elevated to 1623 × 10(6)/ml on the 7th postoperative day. A single thrombocytapheresis procedure reduced her platelet to 403 × 10(6)/ml. She was discharged on the 10th postoperative day and then maintained a count of 204-238 × 10(6)/ml with aspirin. Thrombocytapheresis reduces the platelet count rapidly in thrombocytosis and prevents patients from having thrombotic events. However, such procedures should be performed very meticulously to ensure patient safety. PMID:23871583

  18. Subcutaneous anti-D treatment of idiopathic thrombocytopenic purpura in children.

    PubMed

    Kjaersgaard, Mimi; Edslev, Pernille Wendtland; Hasle, Henrik

    2009-12-15

    We investigated the effect of subcutaneous anti-D IgG as platelet enhancing therapy in children with idiopathic thrombocytopenic purpura (ITP). Twenty-three children were treated with subcutaneous anti-D 50 microg/kg. The median platelet count increased from 7 x 10(9) to 31 x 10(9)/L on day 3 (P < 0.01). The median decline in hemoglobin was 1.3 g/dl. Two children experienced minor fever and chills within 24 hr of treatment. Pain at the injection site was common but self-limiting with no effect on activity level. These results suggest subcutaneous anti-D IgG 50 microg/kg as an effective and well-tolerated treatment option in childhood ITP. PMID:19722275

  19. Refractory chronic immune thrombocytopenic purpura in a child with acute lymphoblastic leukemia.

    PubMed

    Horino, Satoshi; Rikiishi, Takeshi; Niizuma, Hidetaka; Abe, Hiroshi; Watanabe, Yuko; Onuma, Masaei; Hoshi, Yoshiyuki; Sasahara, Yoji; Yoshinari, Miyako; Kazama, Takuro; Hayashi, Yutaka; Kumaki, Satoru; Tsuchiya, Shigeru

    2009-11-01

    Immune thrombocytopenic purpura (ITP) has been associated with several hematologic malignancies such as Hodgkin and non-Hodgkin lymphomas and chronic lymphocytic leukemia, but it is rare in children with acute lymphoblastic leukemia (ALL). Here, we report a 7-year-old girl with chronic ITP during early intensive phase of chemotherapy for ALL. She underwent splenectomy because thrombocytopenia had persisted even after treatment with intravenous immunoglobulin (IVIG), steroids, vincristine, rituximab, and anti-D antibody. After splenectomy, her platelet count had recovered, and maintenance therapy could be resumed with a support of IVIG. To our knowledge, this is the first child case of chronic ITP during chemotherapy for ALL and splenectomy was effective in this patient. PMID:19816666

  20. Risk factors for future development of systemic lupus erythematosus in children with idiopathic thrombocytopenic purpura.

    PubMed

    Hazzan, Rawi; Mukamel, Mashaand; Yacobovich, Joanne; Yaniv, Isaac; Tamary, Hannah

    2006-10-15

    The risk of later development of systemic lupus erythematosus (SLE) in childhood idiopathic thrombocytopenic purpura (ITP) is currently unknown. We retrospectively evaluated the incidence and risk factors of this complication in 222 children with ITP who were followed for a mean of 4.2+/-4.9 years. During that time 3.6% of the children (8/222) developed SLE; all were females with positive anti-nuclear antibody (ANA), older (12.7+/-3.6 vs. 6.4+/-4.3 years old; P<0.01), and were more likely to have chronic ITP (87.5 vs. 46%; P=0.02), and had high titers of ANA. The majority of children with ITP who had a positive ANA (14/22, 64%) did not develop SLE. PMID:16933242

  1. Short-course high-dose dexamethasone therapy for chronic idiopathic thrombocytopenic purpura in children.

    PubMed

    Yadav, Dinesh; Chandra, Jagdish; Sharma, Sunita; Singh, Varinder

    2010-12-01

    First-line therapies of acute and chronic idiopathic thrombocytopenic purpura (ITP) include intravenous immunoglobulin, IV anti-D and corticosteroids. A short-course high-dose dexamethasone (HDD-SC) therapy has recently been reported to be efficacious in acute ITP. The present study was conducted to assess the efficacy of HDD-SC in children with chronic ITP. Over a period of 10 months, 13 patients with chronic ITP were given HDD-SC (20 mg m(-2) IV daily for 4 days, four cycles repeated every 15 days). Of the 12 patients who could be evaluated, complete response was observed in 8 (66.6%) and moderate response in 2 (17%) patients, whereas 2 (17%) patients had no response. HDD-SC appears to be a safe and effective therapy in childhood ITP. PMID:20388659

  2. Management of immune thrombocytopenic purpura in children: potential role of novel agents.

    PubMed

    Bredlau, Amy Lee; Semple, John W; Segel, George B

    2011-08-01

    The treatment of immune thrombocytopenic purpura (ITP) in children is controversial, requiring individualized assessment of the patient and consideration of treatment options. If the platelet count is >10?000/?L and the patient is asymptomatic, a 'watch and wait' strategy is appropriate since most children with ITP will recover completely without pharmacotherapy. If therapy is indicated because of bleeding or a platelet count <10?000/?L, then treatment with glucocorticoids, intravenous immunoglobulin (IVIg), or anti-D are possible initial choices. Glucocorticoid treatment is the least expensive and is our usual first choice of therapy. Its use assumes that the blood counts and blood film have been evaluated to ensure the absence of evidence of alternative diagnoses, such as thrombotic thrombocytopenic purpura or incipient acute leukemia. IVIg is expensive and often causes severe headache, nausea and vomiting, and requires hospitalization at our institution. Anti-D therapy is also expensive and can only be used in patients who are Rhesus D positive. These therapies, even if only transiently effective, can be repeated if necessary. Children usually recover from newly diagnosed ITP, with or without multiple courses of medical therapy. If the disease becomes 'persistent' with severe thrombocytopenia and/or bleeding, and is no longer responsive to the three first-line therapies, the next approach includes the use of thrombopoietin receptor agonists or rituximab. When the disease persists for more than 1 year, it is considered chronic, and, if symptomatic, it may become necessary to consider third-line therapies, including splenectomy, alternative immunosuppressive agents, or combination or investigative chemoimmunotherapy. This review considers the indications, mechanism of action, and effectiveness of the traditional and novel treatment options for patients with ITP. PMID:21692546

  3. Cell-mediated suppression of megakaryocytopoiesis in acquired amegakaryocytic thrombocytopenic purpura.

    PubMed

    Gewirtz, A M; Sacchetti, M K; Bien, R; Barry, W E

    1986-09-01

    Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a disorder of hematopoiesis characterized by severe thrombocytopenia due to a selective reduction or total absence of megakaryocytes in an otherwise normal-appearing bone marrow. Although the development of autoantibodies directed against cells in the megakaryocyte progenitor cell pool has been implicated in the pathogenesis of this disorder, cell-mediated suppression of megakaryocytopoiesis has not been described. Accordingly, we report two cases of AATP in which in vitro suppression of megakaryocyte colony formation by autologous ancillary marrow cells was demonstrable. Light-density bone marrow mononuclear cells (MNCs) obtained from both patients were either plated directly into plasma clot cultures, or after first being depleted by adherent monocytes (M phi) or T lymphocytes using standard methodologies. In some experiments, the depleted ancillary marrow cells were recovered for autologous co-culture studies with the MNCs from which they had been depleted. Megakaryocyte colony formation was detected in the cultures using an indirect immunofluorescence assay with a rabbit anti-human platelet glycoprotein antiserum. Removal of M phi (n = 6), or T lymphocytes (n = 4) from normal marrow MNCs had no apparent effect on colony formation. In contrast, depleting T lymphocytes from the MNCs of patient 1 significantly augmented megakaryocyte colony formation; a similar effect was observed after depleting M phi from the MNCs of patient 2. This observed augmentation in colony formation could be abrogated by autologous co-culture with the putative suppressor cell at effector cell/target cell ratios of 1:10 in the case of T lymphocytes or 1:5 in the case of M phi. Neither suppression nor stimulation of megakaryocyte colony formation was observed after culturing normal MNCs with autologous T cells (n = 4) or M phi (n = 3) at similar or greater ratios. We also observed inhibition of megakaryocyte colony formation after culturing normal MNCs in the presence of tissue culture medium conditioned by the M phi of patient 2. This effect was shown to be specific for megakaryocytes since this same conditioned medium had no significant effect on BFU-E and CFU-E-derived colony formation by autologous marrow mononuclear cells. These results suggest that: both T cells and M phi are capable of exerting a regulatory effect on the proliferation of human megakaryocyte progenitor cells (CFU-Meg); in the case of M phi, a soluble factor elaborated by these cells may be responsible for suppressing CFU-Meg growth; and aberrant ancillary cell-megakaryocyte progenitor cell interactions may lead to clinically significant disease. PMID:3488773

  4. Hemorrhagic Stroke in an Adolescent Female with HIV-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Rakhmanina, Natella; Wong, Edward CC; Davis, Jeremiah C; Ray, Patricio E

    2014-01-01

    HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIV-TTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented with severe thrombocytopenia, microangiopathic hemolytic anemia, and a past medical history of HIV-ITP. Both differential diagnosis and treatments for HIV-ITP and HIV-TTP were considered simultaneously. A decrease in plasma ADAMTS13 activity (<5%) without detectable inhibitory antibodies confirmed the diagnosis of HIV-TTP. Re-initiation of ART and plasma exchange resulted in a marked decrease in the HIV-RNA viral load, recovery of the platelet count, and complete recovery was achieved with sustained virologic suppression. PMID:25429351

  5. Adult primary and secondary immune thrombocytopenic purpura: a comparative analysis of characteristics and clinical course.

    PubMed

    Ayesh, Mahmoud H; Alawneh, Khaldoon; Khassawneh, Basheer; Khader, Yousef; Kasasbeh, Abdullah

    2013-06-01

    This study was conducted to compare the platelet count and the presence of bleeding manifestations at initial diagnosis of immune thrombocytopenic purpura (ITP) between patients with primary and secondary ITP. Medical records for 67 consecutive adult patients with ITP were reviewed retrospectively and the relevant data were abstracted. Thirty-eight (56.7%) patients were diagnosed as having primary ITP and 29 (43.3%) were considered to have secondary ITP. At the time of diagnosis, the median initial platelet count (median: 60 × 10(9)/L) for patients with secondary ITP was significantly (P < .005) higher than that for patients with primary ITP (median: 3.5 × 10(9)/L). Ecchymosis and/or purpura was observed in 4 (13.8%) patients with secondary ITP and in 33 (86.6%) patients with primary ITP (P value <.005). In conclusion, patients with secondary ITP had higher platelet count at diagnosis and were less likely to present with bleeding manifestations than those with primary ITP. PMID:22275396

  6. Excessive naked megakaryocyte nuclei in myelodysplastic syndrome mimicking idiopathic thrombocytopenic purpura: a complicated pre- and post-transplantation course.

    PubMed

    Olcay, Lale; Tuncer, A Murat; Okur, Hamza; Erdemli, Esra; Uysal, Zumrut; Cetin, Mualla; Duru, Feride; Cetinkaya, Duygu Uckan

    2009-09-01

    A boy 3 years 7 months old with thrombocytopenia and history of intracranial hemorrhage who underwent bone marrow transplantation is presented. He was refractory to steroids, immunoglobulin G, vincristine, azathioprine, cyclosporine A, interleukin-11, chemotherapy, and splenectomy. Idiopathic thrombocytopenic purpura was excluded by light /electron microscopic and flow cytometric findings; the diagnosis of refractory cytopenia, a subgroup of pediatric myelodysplastic syndrome, was made. Naked megakaryocyte nuclei were 55.38 +/- 28.2% vs. 31.67 +/- 23.22% of all megakaryocytes in the patient and the control group of 9 patients with idiopathic thrombocytopenic purpura, respectively (p = .016). The posttransplatation course was complicated by delayed platelet engraftment, bronchiolitis obliterans associated with pneumocystis carinii pneumonia, which resolved completely. PMID:19657988

  7. Successful treatment of acquired amegakaryocytic thrombocytopenic purpura refractory to corticosteroids and intravenous immunoglobulin with antithymocyte globulin and cyclosporin.

    PubMed

    Niparuck, Pimjai; Atichartakarn, Vichai; Chuncharunee, Suporn

    2008-09-01

    Four patients with acquired amegakaryocytic thrombocytopenic purpura, who had failed corticosteroids, intravenous immunoglobulin and cyclophosphamide therapy, were treated with antithymocyte globulin, followed by cyclosporin. Three patients achieved complete remission in 28-178 days and the response duration was 16-60 months from the beginning of treatment. One patient achieved a partial response for 2 months followed by myelodysplastic syndrome 5 months later. He died in 9 months due to intracerebral bleeding. Marrow cytogenetics showed 47, XY, +21. PMID:18626728

  8. Effect of thymectomy on myasthenia gravis and autoimmune thrombocytopenic purpura in a 13-year-old girl

    Microsoft Academic Search

    P. H. P. Jansen; W. O. Renier; G. de Vaan; P. Reekers; D. M. Vingerhoets; F. J. M. Gabreëls

    1987-01-01

    We report the association of myasthenia gravis (MG) and autoimmune thrombocytopenic purpura (AITP) in a 13-year-old girl.\\u000a The co-existence of these autoimmune diseases is rare in adults and, to our knowledge, never described in children. In our\\u000a patient thymectomy had a therapeutic effect on both MG and AITP, suggesting a altered T-cell function as a pathogenic factor\\u000a of major importance

  9. Idiopathic Thrombocytopenic Purpura: Better Therapeutic Responses of Patients with B or T-Cell Clonality than Patients without Clonality

    Microsoft Academic Search

    J. Kim; C. J. Park; H. S. Chi; M. J. Kim; J. J. Seo; H. N. Moon; T. T. Ghim; S. W. Kim; J. H. Lee; G. H. Lee

    2003-01-01

    Results of recent studies of the pathogenesis of idiopathic thrombocytopenic purpura (ITP) have suggested activated helper\\u000a T-cells drive B-lymphocytes to produce antibodies. Twenty-eight children and 85 adults with ITP entered this study. We performed\\u000a polymerase chain reaction (PCR) using framework III variable region (VH FRIII)- and joining region (JH)-specific primers to analyze immunoglobulin heavy-chain gene rearrangement (IgH GR) for B-cell

  10. Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets

    SciTech Connect

    Stratton, J.R.; Ballem, P.J.; Gernsheimer, T.; Cerqueira, M.; Slichter, S.J.

    1989-05-01

    Using autologous /sup 111/In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction.

  11. Vaccine administration and the development of immune thrombocytopenic purpura in children.

    PubMed

    Cecinati, Valerio; Principi, Nicola; Brescia, Letizia; Giordano, Paola; Esposito, Susanna

    2013-05-01

    The most important reasons cited by the opponents of vaccines are concerns about vaccine safety. Unlike issues such as autism for which no indisputable documentation of direct relationship with vaccine use is available, immune thrombocytopenic purpura (ITP) is an adverse event that can really follow vaccine administration, and may limit vaccine use because little is known about which vaccines it may follow, its real incidence and severity, the risk of chronic disease, or the possibility of recurrences after new doses of the same vaccine. The main aim of this review is to clarify the real importance of thrombocytopenia as an adverse event and discuss how it may interfere with recommended vaccination schedules. The available data clearly indicate that ITP is very rare and the only vaccine for which there is a demonstrated cause-effect relationship is the measles, mumps and rubella (MMR) vaccine that can occur in 1 to 3 children every 100,000 vaccine doses. However, also in this case, the incidence of ITP is significantly lower than that observed during the natural diseases that the vaccine prevents. Consequently, ITP cannot be considered a problem limiting vaccine use except in the case of children suffering from chronic ITP who have to receive MMR vaccine. In these subjects, the risk-benefit ratio of the vaccine should be weighed against the risk of measles in the community. PMID:23324619

  12. DNMT3B promoter polymorphism and risk of immune thrombocytopenic purpura in pediatric Egyptians.

    PubMed

    Shaheen, Iman A; Abukhalil, Reham E; Ali, Dina K; Afifi, Rasha A

    2012-10-01

    Idiopathic (immune) thrombocytopenic purpura (ITP) is a heterogeneous clinical disorder characterized by immune-mediated platelet destruction. Epigenetic changes in gene expression, including DNA methylation and histone modifications, might contribute to autoimmunity. Polymorphisms of the DNA methyltransferase 3B (DNMT3B) gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between a single nucleotide polymorphism (SNP) in the promoter of DNMT3B gene and the risk for ITP in pediatric Egyptians. DNMT3B SNP was genotyped by PCR-restriction fragment length polymorphism in 71 pediatric ITP patients and 82 healthy controls matched for age and sex. The C/C wild genotype was not detected in ITP patients or in the controls. The frequencies of the T/T and C/T genotypes were 93.9 and 6.1% in the controls and 91.5 and 6.1% in ITP patients, respectively. There was no significant difference in either genotypes or allelic distribution between ITP patients and the controls. In conclusion, this polymorphism was almost equally distributed between ITP patients and the controls. These results demonstrated that this SNP may not be used as a stratification marker to predict the susceptibility to childhood ITP in Egypt. PMID:22885766

  13. [Successful rituximab treatment for acquired amegakaryocytic thrombocytopenic purpura complicated with Coombs-negative autoimmune hemolytic anemia].

    PubMed

    Hashimoto, Akari; Fujimi, Akihito; Kanisawa, Yuji; Matsuno, Teppei; Okuda, Toshinori; Minami, Shinya; Doi, Tadashi; Ishikawa, Kazuma; Uemura, Naoki; Tomaru, Utano

    2013-06-01

    Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disorder characterized by severe thrombocytopenia associated with total absence or a selective decrease in bone marrow megakaryocytes. A 67-year-old male presented with a 2-month bleeding tendency. He was referred to our hospital because of severe thrombocytopenia. Bone marrow biopsy showed complete absence of megakaryocytes without dysplasia in cells of the myeloid and erythroid lineages. AATP was diagnosed. In addition, mild normocytic normochromic anemia and reticulocytosis were also observed and haptoglobin was below the detectable level. Coombs-negative autoimmune hemolytic anemia (AIHA) was diagnosed based on the high titer of RBC-bound IgG and negative direct and indirect coombs test results. He was first treated with cyclosporine 200 mg per day and subsequently with prednisolone but only slight temporary improvement was achieved. Administration of eight doses of rituximab 375 mg/m(2) per week ameliorated both thrombocytopenia and anemia. AATP should be considered in the differential diagnosis of thrombocytopenia, and immunosuppressive therapy is a potential first-line treatment. This is the first case report of AATP accompanied by AIHA successfully treated with rituximab. PMID:23823096

  14. A 35-year-old woman with influenza A-associated thrombotic thrombocytopenic purpura.

    PubMed

    Jonsson, Maria K; Hammenfors, Daniel; Oppegaard, Oddvar; Bruserud, Øystein; Kittang, Astrid Olsnes

    2015-06-01

    A previously healthy 35-year-old woman presented with severe thrombotic thrombocytopenic purpura (TTP) affecting several organs and concomitant influenza A infection. On admission to hospital, haemoglobin was 5.4?g/dl, platelet count 6?×?10/l, Schistocyte count in peripheral blood 5%, and throat swab positive for influenza A RNA. The patient was treated with antiviral medication and transfusions of fresh frozen plasma before plasma exchange therapy with excellent response. Plasmaphereses were attenuated after 5 days, resulting in TTP relapse 3 days later. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) protein was very low (<0.04?U/l) and anti-ADAMTS13 elevated (>2?U/l), consistent with acquired TTP. Platelet counts normalized after five additional plasma exchanges and oral corticosteroids. Antinuclear antibodies and subgroup anti-Ro/Sjögren's syndrome A antigen (SSA) were detected in serum and have remained borderline-elevated, although evaluation during TTP, recovery and follow-up have lacked clinical manifestations of connective tissue disease. Influenza A infection induced production of ADAMTS13 inhibitor, which resulted in TTP in a patient with circulating antinuclear antibodies, lacking other manifestations of connective tissue disease. PMID:25688460

  15. A case of myelitis with anti-aquaporin 4 antibody concomitant with immune thrombocytopenic purpura.

    PubMed

    Mizuno, Hideki; Sato, Shigeru; Ohnishi, Yasushi; Takahashi, Toshiyuki; Nakashima, Ichiro; Fujihara, Kazuo; Aoki, Masashi; Ohnuma, Ayumu

    2014-01-01

    We report a 44-year-old woman who had anti-aquaporin 4 (AQP4) antibody-positive myelitis and immune thrombocytopenic purpura (ITP). She was admitted to our hospital with paraparesis, dysesthesia below the Th8 dermatome level on her right side and lower extremities, constipation and urinary retention. Magnetic resonance imaging revealed a longitudinally extending lesion at the level of Th4-Th10. Her serum sample was positive for anti-AQP4 antibody. Corticosteroid therapy was initiated, and her symptoms were largely ameliorated. Furthermore, concurrently with the myelitis, her platelet count dropped (99 × 10(9)/l). A diagnosis of ITP was made with positive serum platelet-associated IgG (PA-IgG) and negative work-up for blood malignancies by bone marrow aspiration. Since a causal relationship between Helicobacter pylori (H. pylori) and ITP is suggested by several studies, she was also examined and diagnosed with H. pylori-positive ITP. After the bacteria eradication therapy, her platelet count and PA-IgG returned to normal range. Furthermore, the anti-AQP4 antibody titer declined and her symptoms were almost resolved. We considered that H. pylori might influence progression of the myelitis as well as induction and development of ITP. PMID:24705832

  16. Refractory thrombotic thrombocytopenic purpura associated with primary Sjogren syndrome treated with rituximab: a case report.

    PubMed

    Toumeh, Anis; Josh, Navpreet; Narwal, Rawan; Assaly, Ragheb

    2014-01-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon, serious disease that involves multiple organs and is rapidly fatal if left untreated. TTP is associated with multisystem symptoms, such as thrombocytopenia, microangiopathic hemolytic anemia, renal impairment, central nervous system involvement, and fever. TTP is idiopathic in about 37% of the cases and can be associated with autoimmune diseases in 13% of the cases. Autoimmune disease-associated TTP can be refractory to plasma exchange and requires immunosuppressive therapy. We report a case of a previously healthy 55-year-old African American female who presented with shortness of breath, hemolytic anemia, renal impairment, and thrombocytopenia. The diagnosis of TTP was made, and plasmapheresis was initiated. However, recurrence happened 48 hours after plasmapheresis was stopped. Autoimmune workup for refractory TTP revealed positive antinuclear antibodies, Anti-SSA, and Anti-SSB. Lip biopsy revealed findings consistent with Sjogren syndrome. Treatment with Rituximab was started, and significant clinical and laboratory response was achieved. The patient remained asymptomatic thereafter. A high clinical suspicion of autoimmune diseases is important as TTP tends to be refractory to plasma exchange in these cases, and immunosuppressive therapy is a key. PMID:23011161

  17. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

    PubMed Central

    Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

    2008-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

  18. Immunologic effects of anti-D (WinRho-SD) in children with immune thrombocytopenic purpura.

    PubMed

    Zimmerman, S A; Malinoski, F J; Ware, R E

    1998-02-01

    Intravenous immunoglobulin (IVIG) is an effective treatment for immune thrombocytopenic purpura (ITP) that induces transient blockade of the reticuloendothelial system (RES) with additional effects including alteration of T lymphocyte subsets and suppression of in vitro T lymphocyte proliferation. As anti-D also is an effective treatment for ITP, we investigated its in vitro and in vivo immunologic effects. The in vitro effects of various agents used in ITP therapy were compared using T lymphocyte proliferation assays. Anti-D caused significantly less inhibition than IVIG or dexamethasone, but non-specific protein was as suppressive as IVIG. Six children with chronic ITP were studied following anti-D administration. Patients received a single dose of anti-D (WinRho-SD, 50 microg/kg i.v. over 5 min) and were studied on day 0, day 7, and 1 month later. Anti-D did not affect T lymphocyte subsets including the T cell receptor variable beta repertoire, in vitro T lymphocyte proliferation to mitogens, recall antigens, or interleukin-2, in vitro IgG synthesis induced by pokeweed mitogen, or T lymphocyte cytokine mRNA levels. We conclude that anti-D has no demonstrable in vitro or in vivo effects on lymphocyte enumeration or function, and therefore likely is effective in the treatment of ITP primarily through RES blockade. PMID:9462545

  19. Platelet antibodies of the IgM class in immune thrombocytopenic purpura

    SciTech Connect

    Cines, D.B.; Wilson, S.B.; Tomaski, A.; Schreiber, A.D.

    1985-04-01

    The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, the authors studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. They observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP. They obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3. The authors demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.

  20. Cost-effectiveness of treatment for acute childhood idiopathic thrombocytopenic purpura (ITP)--a systematic review.

    PubMed

    Chen, M; Zhang, L-L; Hu, M; Gao, J; Tong, R-S

    2008-01-01

    The cost-effectiveness of treatment for acute paediatric idiopathic thrombocytopenic purpura (ITP) was assessed to provide evidence for health-care decision making and rational drug use. A systematic review of studies published between 1980 and 7 September 2007 on the clinical effects and economic profiles of treating ITP was undertaken. The quality of the studies was critically appraised and checklists were developed to assess methodological quality and transferability to the Chinese setting. Out of 174 studies, five (one Chinese; four USA) satisfied all the predefined criteria for inclusion and form the basis of this report. Methodological quality of most of the foreign studies was high, but transferability to other countries was low. Use of steroids provided additional life years and was cost-effective compared with intravenous immunoglobulin G and anti-D immunoglobulin. In comparison, the quality of the Chinese studies was low and long-term research rare. It was difficult to compare cost-effectiveness in different health-care settings and no lifetime economic evaluations were available. PMID:18534141

  1. Multiagent induction and maintenance therapy for patients with refractory immune thrombocytopenic purpura (ITP).

    PubMed

    Boruchov, Donna M; Gururangan, Sri; Driscoll, M Catherine; Bussel, James B

    2007-11-15

    Patients with severe immune thrombocytopenic purpura (ITP) may require an acute increase in the platelet count for surgery or ongoing hemorrhage as well as long-term maintenance treatment. Certain of these patients may be refractory to steroids, intravenous anti-D, intravenous immunoglobulin (IVIG), and splenectomy. Therefore, acute platelet increases were studied in 35 patients completely unresponsive to IVIG or high-dose steroid treatment. Because of their lack of response to either or both single agents, these patients were administered a 3- or 4-drug combination including IVIG 1 g/kg, intravenous methylprednisolone 30 mg/kg, Vinca alkaloids (VCR 0.03 mg/kg), and/or intravenous anti-D (50-75 microg/kg). Subsequent maintenance therapy with the oral combination of danazol (10-15 mg/kg) and azathioprine (2 mg/kg) was given to 18 of the 35 patients. Seventy-one percent of the patients responded to the intravenous combination treatment with acute platelet increases of at least 20 x 10(9)/L to a level greater than 30 x 10(9)/L. Two thirds of the patients given maintenance therapy achieved stable platelet counts greater than 50 x 10(9)/L without other treatments. One patient developed an ileus, but otherwise there was little toxicity of combination treatment. Combination chemotherapy is a useful approach for patients with ITP refractory to conventional treatments both for acute induction and for long-term maintenance therapy. PMID:17698634

  2. [Treatment of chronic immune thrombocytopenic purpura. Looking for something better. Review].

    PubMed

    Vizcaíno, Gilberto; Diez-Ewald, María; Vizcaíno-Carruyo, Jennifer

    2009-03-01

    Chronic Immune Thrombocytopenic Purpura (cITP) has become a field of multiple therapeutic assays. More than 20 types of treatment have been developed to obtain a favorable and prolonged platelet response. The treatment of cITP is oriented to inhibit the antiplatelet antibodies production by interference with the macrophage of the reticulum endothelial system and a blockade of the antigenic response with a decrease in the amplification of the immunological response. Steroids of the glucocorticoids type and splenectomy constitute the first line of treatment. Failure of these treatments leads to the use of second line drugs such as non steroid immuno-supressors and the immunoglobulins type IgG and anti-D. Therapeutic assays with others immunomodulators have been reported. The introduction of new drugs destined to increase the megakaryocytic bone marrow platelet production, has opened a new way to treat the cITP. However, the splenectomy remains as the simplest, safest and most effective treatment in cITP. The principal criteria does not have to be focused on obtaining a normal platelet count, but to reach safe hemostatic levels in absence of hemorrhage, for a prolonged time. On the other hand, despite the persistence of thrombocytopenia, the hematologist can choose to maintain the patient with no treatment and with only a strict clinical observation. It is obvious that the cost-benefit from the different treatments is inclined towards those of lower cost and minimal secondary effects. PMID:19418731

  3. Prognostic value of inhibitory anti-ADAMTS13 antibodies in adult-acquired thrombotic thrombocytopenic purpura.

    PubMed

    Coppo, P; Wolf, M; Veyradier, A; Bussel, A; Malot, S; Millot, G A; Daubin, C; Bordessoule, D; Pène, F; Mira, J P; Heshmati, F; Maury, E; Guidet, B; Boulanger, E; Galicier, L; Parquet, N; Vernant, J P; Rondeau, E; Azoulay, E; Schlemmer, B

    2006-01-01

    In order to assess the prognostic value of inhibitory anti-ADAMTS13 antibodies in thrombotic thrombocytopenic purpura (TTP), we performed a multicentre prospective study of 33 adult patients with idiopathic acquired TTP. Patients were treated with high-dose plasma infusion and therapeutic plasma exchange. Patients without (group 1, n = 12) and with (group 2, n = 21) detectable inhibitory anti-ADAMTS13 antibodies were compared for clinical presentation, treatment and outcome. Both groups were comparable for clinical presentation. All patients in group 1 achieved a sustained complete remission within a median of 7 d [95% confidence interval (CI), 4-18], which required a median plasma volume of 235 ml/kg (range, 131-1251). In group 2, 17 patients achieved a durable complete remission within a median of 23 d (95% CI, 11-32) (P = 0.001). Median plasma volume was 718 ml/kg (range, 219-3107) (P = 0.02). In group 2, there was a trend for more episodes of flare-up than in group 1 (13 vs. 3, respectively, P = 0.07). Four patients, all from group 2, died (P = not significant). The relapse rate was comparable between both groups. We suggest that TTP with detectable inhibitory anti-ADAMTS13 antibodies displays a worse prognosis, relative to a delayed platelet count recovery, a higher plasma volume requirement to achieve complete remission, and a trend for more frequent episodes of flare-up. PMID:16371021

  4. Long-term results of laparoscopic splenectomy in pediatric chronic immune thrombocytopenic purpura

    PubMed Central

    Kim, Dong Jin

    2014-01-01

    Purpose Laparoscopic splenectomy (LS) for pediatric chronic immune thrombocytopenic purpura (ITP) patients has recently become widespread. However, its long-term result is rarely reported in children. Methods We retrospectively analyzed the patients who underwent LS for pediatric chronic ITP from June 1998 to April 2007. Results There were 18 patients (14 male and 4 female) with mean age 9.5 ± 3.8 years. 14 complete response, 3 partial response, and 1 no response were occurred. During the 82-month median follow-up period, 9 patients maintained in a remission state without any additional treatment, and 9 patients relapsed. In a comparative analysis of the relapse group and no relapse group, hospital stays were longer in the relapse group and the preoperative platelet counts and platelet counts at 1 month post were lower in relapse group. A relapse-free survival among 17 patients who achieved partial or complete responses following LS showed 76.5%, 61.8%, and 33.0% at 1-, 5-, and 10-year following LS, respectively. Conclusion Although LS in pediatric chronic ITP patients had excellent results immediately after surgery, careful follow up is needed due to late relapse even when a complete response has been noted for several years. PMID:24949323

  5. Two Cases and Review of the Literature: Primary Percutaneous Angiography and Antiplatelet Management in Patients with Immune Thrombocytopenic Purpura

    PubMed Central

    Torbey, Estelle; McCord, Donald; Lafferty, James

    2013-01-01

    We report two cases of immune thrombocytopenic purpura (ITP) associated with acute coronary artery syndrome highlighting the interventions done in every case along with the medications used during intervention and as outpatient. The first case is that of a woman with ITP exacerbation while on dual antiplatelet therapy and the second case is that of a male presenting with non-ST elevation myocardial infarction (NSTEMI) while in a thrombocytopenic crisis. In both cases antiplatelet therapy was held and thrombopoietic therapy was initiated before resuming full anticoagulation and coronary intervention. Given the paucity of data on ITP and antiplatelets treatment in the setting of acute coronary syndrome, no strict recommendations can be proposed, but antiplatelets appear to be safe acutely and in the long term in this category of patients as long as few measures are undertaken to minimize the risks of bleeding and thrombosis. PMID:24459590

  6. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in relapsing-remitting multiple sclerosis patients on high-dose interferon ?.

    PubMed

    Larochelle, Catherine; Grand'maison, François; Bernier, Gilles P; Latour, Mathieu; Cailhier, Jean-François; Prat, Alexandre

    2014-11-01

    Three women aged 34-47 years old, on high dose interferon beta-1a for relapsing-remitting multiple sclerosis, were hospitalized between 2009-2012 for thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Patients sought medical attention for neurological symptoms including cephalalgia, blurred vision, confusion, focal deficits and seizures. All patients presented thrombocytopenia, hemolytic anemia and arterial hypertension. Despite plasma exchanges, corticosteroids and anti-CD20 treatments, all patients progressed towards severe renal insufficiency and one patient died of hemorrhagic shock. In this report we identify a rare but morbid complication of interferon beta-1a treatment associated with female gender, Caucasian background and low body mass index. PMID:24534079

  7. Thrombotic thrombocytopenic purpura precipitated by acute pancreatitis: a report of seven cases from a regional UK TTP registry.

    PubMed

    McDonald, V; Laffan, M; Benjamin, S; Bevan, D; Machin, S; Scully, M A

    2009-02-01

    Thrombotic thrombocytopenic purpura (TTP) may be idiopathic or secondary. We report seven TTP cases precipitated by pancreatitis. The patients were admitted with acute pancreatitis and at that time had no clinical or laboratory features of TTP. The median time to develop TTP after pancreatitis was 3 d. The patients had moderately reduced ADAMTS13 activity (mean activity 49%; normal range 66-126%) with no evidence of anti-ADAMTS13 inhibitory autoantibodies. The median number of plasma exchanges to remission was 10 (range 7-14) and no additional treatment with immunosuppression was required to maintain remission. There have been no relapses to date. PMID:19036107

  8. Hepatitis C Virus Infection Among Patients with Chronic Immune Thrombocytopenic Purpura in Northern India

    PubMed Central

    Varma, Subhash; Kumar, Shiv; Garg, Ashish; Malhotra, Pankaj; Das, Ashim; Sharma, Arpita; Chawla, Yogesh K; Dhiman, Radha K

    2011-01-01

    Background Hepatitis C virus (HCV) has been reported to be associated with the occurrence of autoimmune disorders, including immune thrombocytopenic purpura (ITP). This has suggested that HCV could be responsible for thrombocytopenia in these patients. This study was performed to estimate the frequency of HCV infection in patients of chronic ITP (cITP), and to find the frequency of thrombocytopenia in chronic HCV infection. Materials A total of 150 subjects were included in the study. Fifty consecutive adult patients with cITP (< 6 months' duration) and 50 age-matched patients with chronic HCV were included for comparison of platelet counts in two groups. Fifty age-matched healthy subjects were also included in the control group. All patients' sera were tested for the presence or absence of HCV-RNA. Anti-HCV antibodies were tested in patients as well as in controls. Complete blood count and examination of peripheral blood smear were done followed by bone-marrow aspiration to confirm the diagnosis of ITP. Results Three patients (6%) were tested positive for anti-HCV antibodies while no subject was positive in control group (P=0.24). The prevalence of severe thrombocytopenia (platelet counts <50,000/mL) was significantly higher in ITP patients compared with that in chronic HCV patients (P=0.0001). Thrombocytopenia occurred more frequently in patient with moderate to severe than mild stage of fibrosis (P=0.001). Conclusion In conclusion, thrombocytopenia in ITP patients was not associated with HCV infection. The prevalence of thrombocytopenia was more common and more severe in ITP patients when compared with that in patients with chronic HCV. Thrombocytopenia in chronic HCV patients was related to the stage of fibrosis and to the duration of HCV infection. PMID:25755317

  9. Decreased plasma cytokines associate with low platelet counts in aplastic anemia and immune thrombocytopenic purpura

    PubMed Central

    Feng, Xingmin; Scheinberg, Phillip; Samsel, Leigh; Rios, Olga; Chen, Jichun; McCoy, J. Philip; Ghanima, Waleed; Bussel, James B.; Young, Neal S.

    2012-01-01

    Summary Background We previously found plasma levels of CD40 ligand (CD40L), chemokine (C-X-C motif) ligand 5 (CXCL5), chemokine (C-C motif) ligand 5 (CCL5), and epidermal growth factor (EGF) to be low in aplastic anemia (AA) patients and to be correlated with the platelet count. Objectives To study the association of CD40L, CXCL5, CCL5, and EGF with platelets. Patients/Methods We measured cytokines in the plasma of immune thrombocytopenic purpura (ITP) and AA patients using the Luminex assay and confirmed the results in a mouse model and in vitro experiments. Results Both ITP and AA showed similarly low levels of CD40L, CXCL5, CCL5, and EGF, compared with healthy controls. In ITP, levels of these proteins were significantly greater in patients with higher platelet counts than in those with lower platelet counts. In a murine thrombocytopenia model, levels of CD40L, CXCL5, CCL5, and EGF decreased with platelet count after immune-mediated destruction, while the cytokine levels increased when the platelet count recovered. In vitro, concentrations of these cytokines in the supernatants of platelet suspensions were proportional to platelet numbers, and levels in sera prepared by simple blood coagulation were equivalent to those in platelet-rich plasma-converted sera. mRNA expression for CXCL5, CCL5, and EGF was higher in platelets than in megakaryocytes, peripheral blood mononuclear cells, granulocytes, and non-megakaryocytic bone marrow cells. Conclusions Plasma CD40L, CXCL5, CCL5, and EGF are mainly platelet-derived, suggesting a role of platelets in immune responses and inflammation. Measurement of CD40L, CXCL5, CCL5, and EGF in human blood allowed testable inferences concerning physiology and pathophysiology in quantitative platelet disorders. PMID:22537155

  10. Platelet antibodies of the IgM class in immune thrombocytopenic purpura.

    PubMed Central

    Cines, D B; Wilson, S B; Tomaski, A; Schreiber, A D

    1985-01-01

    The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, we studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. We observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP (less than 10%), (P less than 0.01). We obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3 (P less than 0.01, r = 0.53). We demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. The isolated IgM fraction from these two plasmas was able to activate complement and place 3H-C3 on normal platelets. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP. PMID:4039335

  11. [Clinical significance of Helicobacter pylori in children with idiopathic thrombocytopenic purpura].

    PubMed

    Tang, Ying; Wang, Shu-Chun; Wang, Lu-Juan; Liu, Yong; Wang, Hai-Ying; Wang, Zhan-Ju

    2013-04-01

    This study was aimed to investigate the clinic significance of helicobacter pylori (HP) in children with idiopathic thrombocytopenic purpura (ITP). The infection of HP in 92 ITP children was determined by (13) C-Urea Breath Test, the same test was also performed on 66 healthy children. The 68 children infected with HP were randomly divided into 2 groups: single drug group treated only with corticosteroid and; combined drug group treated with corticosteroid and anti-helicobacter pylori treatment. The results showed that 68 patients infected with HP were found in 92 ITP children (74.7%), 26 patients infected with HP were observed in 66 healthy children (39.4%), which was lower than that in ITP children (74.7%, P < 0.05). After anti-helicobacter pylori therapy, the total effective rate and cure rate of ITP patients increased respectively from 73.5% to 94.1%, and the total recurrence rate (17.0%) was much lower than single drug group (47.1%, P < 0.05). Otherwise, after therapy the platelet count in both two groups increased continuously, and at the same time point, the platelet count in anti-helicobacter pylori group was higher than that in the single drug group (P < 0.05). It is concluded that the ITP children have a higher infection rate of HP, which may be involved in the pathogenesis of ITP. Anti-helicobacter pylori therapy would help to improve the therapeutic efficacy and reduce the recurrence of ITP children. PMID:23628045

  12. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients.

    PubMed

    Scaradavou, A; Woo, B; Woloski, B M; Cunningham-Rundles, S; Ettinger, L J; Aledort, L M; Bussel, J B

    1997-04-15

    We report the results of intravenous anti-D (WinRho, WinRho SD) therapy in 261 non-splenectomized patients treated at the New York Hospital-Cornell Medical Center over the period from 1987 to 1994. Children (n = 124) and adult patients (n = 137) with classic immune thrombocytopenic purpura (ITP; n = 156) or human immunodeficiency virus (HIV) related thrombocytopenia (n = 105) and acute (n = 75) or chronic (n = 186) disease at the time of the initial anti-D treatment were studied. In addition, 11 previously splenectomized patients were treated as a separate group. Our objectives were to evaluate the following. (1) Efficacy of anti-D: The response after the initial infusion was analyzed according to clinical parameters, such as patient's age, HIV status, gender, disease duration, pretreatment platelet count, and hemoglobin value, as well as treatment-related factors, including the dose of anti-D, the solvent detergent treatment of the preparation, and the type of administration. (2) Use of anti-D as maintenance therapy: The duration of response after the initial infusion and the results of subsequent treatments were evaluated. (3) Safety/toxicity of anti-D: Postinfusion reactions and hemoglobin decrease after treatment were studied. Anti-D is a safe treatment providing a hemostatic platelet increase in greater than 70% of the Rh+ non-splenectomized patients. The group with the best results is HIV- children, but all patient groups respond and the effect lasts more than 21 days in 50% of the responders. Duration of response is not influenced by HIV status; furthermore, HIV+ patients show no adverse effects on hemoglobin decrease or HIV disease progression. Patients with chronic ITP after splenectomy have minimal or no response to intravenous anti-D. PMID:9108386

  13. DIFFERENT DISPARITIES OF GENDER AND RACE AMONG THE THROMBOTIC THROMBOCYTOPENIC PURPURA AND HEMOLYTIC-UREMIC SYNDROMES

    PubMed Central

    Terrell, Deirdra R.; Vesely, Sara K.; Kremer Hovinga, Johanna A.; Lämmle, Bernhard; George, James N.

    2012-01-01

    Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) represent multiple disorders with diverse etiologies. We compared the gender and race of 335 patients enrolled in the Oklahoma TTP-HUS Registry across 21 years for their first episode of TTP or HUS to appropriate control groups. The relative frequency of women and white race among patients with TTP-HUS associated with a bloody diarrhea prodrome and the relative frequency of women with quinine-associated TTP-HUS were significantly greater than their control populations. The relative frequency of women and black race among patients with idiopathic TTP and TTP associated with severe ADAMTS13 deficiency was significantly greater than their control populations. The relative frequency of black race among patients who had systemic lupus erythematosus (SLE) preceding TTP was significantly greater than among a population of patients with SLE, and the relative frequency of black race among patients with other autoimmune disorders preceding TTP was significantly greater than their control population. No significant gender or race disparities were present among patients with hematopoietic stem cell transplantation-associated thrombotic microangiopathy, TTP associated with pregnancy, or TTP associated with drugs other than quinine. The validity of these observations is supported by the enrollment of all consecutive patients across 21 years from a defined geographic region, without selection or referral bias. These observations of different gender and race disparities among the TTP-HUS syndromes suggest the presence of different risk factors and may serve as starting points for novel investigations of pathogenesis. PMID:20799358

  14. Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic thrombocytopenic purpura

    PubMed Central

    Khanal, Nabin; Dahal, Sumit; Upadhyay, Smrity; Bierman, Philip J.

    2015-01-01

    Objectives: Malignant hypertension can cause thrombotic microangiopathy (TMA) and the overall presentation may mimic thrombotic thrombocytopenic purpura (TTP). This presents a dilemma of whether or not to initiate plasma exchange. The objective of the study was to determine the clinical and laboratory manifestations of malignant hypertension-induced TMA, and its outcomes. Methods: Using several search terms, we reviewed English language articles on malignant hypertension-induced TMA, indexed in MEDLINE by 31 December 2013. We also report a new case. All these cases were analyzed using descriptive statistics. Results: A total of 19 patients, with 10 males, had a median age of 38 years at diagnosis; 58% had a history of hypertension. Mean arterial pressure at presentation was 159?mmHg (range 123–190?mmHg). All had prominent renal dysfunction (mean creatinine of 5.2?mg/dl, range 1.7–13?mg/dl) but relatively modest thrombocytopenia (mean platelet count of 60?×?103/µl, range 12–131?×?103/µl). Reported cases (n?=?9) mostly had preserved ADAMTS-13 activity (mean 64%, range 18–96%). Following blood pressure control, the majority had improvement in presenting symptoms (100%) and platelet counts (84%); however, only 58% had significant improvement in creatinine. More than half (53%) needed hemodialysis. One patient died of cardiac arrest during pacemaker insertion. Conclusion: Prior history of hypertension, high mean arterial pressure, significant renal impairment but relatively modest thrombocytopenia and lack of severe ADAMTS-13 deficiency (activity <10%) at diagnosis are clues to diagnose malignant hypertension-induced TMA. Patients with malignant hypertension respond well to antihypertensive agents and have favorable nonrenal outcomes.

  15. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

    PubMed

    Frydman, Galit H; Davis, Nick; Beck, Paul L; Fox, James G

    2015-08-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state. PMID:25728540

  16. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group

    Microsoft Academic Search

    Francesco Rodeghiero; Roberto Stasi; Terry Gernsheimer; Marc Michel; Drew Provan; Donald M. Arnold; James B. Bussel; Douglas B. Cines; Beng H. Chong; Nichola Cooper; Bertrand Godeau; Klaus Lechner; Maria Gabriella Mazzucconi; Robert McMillan; Miguel A. Sanz; Paul Imbach; Victor Blanchette; Thomas Kuhne; Marco Ruggeri; James N. George

    Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scien- tific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of exist- ing data is a lack of consensus on stan- dardized critical definitions, outcome cri- teria,

  17. Correction of abnormal T cell subsets by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura.

    PubMed

    Li, Jianqin; Wang, Zhaoyue; Hu, Shaoyan; Zhao, Xiaojuan; Cao, Lijuan

    2013-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an acquired autoimmune disorder. Both impaired platelet production and T cell-mediated effects play a role in ITP thrombocytopenia. A Th1 polarization of the immune response, up-regulation of Th17 cells and decreased number of Treg cells have been demonstrated in ITP patients. High-dose dexamethasone was administered as first-line therapy in adult patients with ITP. However, the mechanism of effects of dexamethasone on ITP is still unclear. In this study, we tested the effectiveness of high-dose dexamethasone as initial treatment in adults with immune thrombocytopenic purpura. PBMCs were isolated from Donors, ITP and Treatment groups. T cell subsets were analyzed by FCM and transcriptional factors were checked by Real-time PCR. We found that dexamethasone returned the ratio of Th1/Th2 and the number of Th17 and Treg cells to the normal levels. Furthermore, we identified that dexamethasone corrected the T cell subset levels through inhibiting GATA3 and FOXp3 expression and promoting ROR?t expression. Taken together, we reported a previously unrecognized mechanism on dexamethasone in the ITP treatment. PMID:23994430

  18. Safety and Efficacy of Gammaplex® in Idiopathic Thrombocytopenic Purpura (ClinicalTrials.gov - NCT00504075)

    PubMed Central

    Dash, Clive H.; Gillanders, Kate R.; Stratford Bobbitt, Margaret E.; Gascoigne, Ernie W.; Leach, Samantha J.

    2014-01-01

    Background and Objectives This multicentre, open-label study investigated the safety and efficacy of Gammaplex, a 5% Intravenous Immunoglobulin (IVIg), in patients with idiopathic (immune) thrombocytopenic purpura (ITP). Materials and Methods Patients were between the ages of 6 and 70 years; had ITP for at least six months and had a platelet count ?20×109/L. Eligible patients were dosed with 1 g/kg of Gammaplex on two consecutive days, followed by assessment of safety and efficacy on Days 3, 5, 9, 14, 21, 32 and 90. Response was defined as the increase in platelet count to a threshold of ?50×109/L on or before Day 9 after the first dose of Gammaplex. Results All 35 patients received at least one infusion of Gammaplex. Twenty-nine (83%) patients responded to Gammaplex, similar to the historical control, with a 95% lower one-sided confidence interval of 68.9%. Median duration of response was 10.0 days, with an overall reduction in bleeding episodes. Gammaplex provided supranormal concentrations of total IgG; mean peak concentration (Cmax) of 45.3 g/L (4.53 g/dL), with a mean half-life of 28.5 days. Fifteen patients reported 63 Adverse Drug Reactions (ADRs); the most common were headache (10 patients), vomiting (6 patients) and pyrexia (5 patients). Five of these ADRs were considered serious, one patient had three concurrent Serious Adverse Events (SAEs); these were vomiting, dehydration and headache. Two other patients each had one SAE (headache). There were no unexpected Adverse Events (AEs) or thromboembolic episodes and no significant changes in vital signs, biochemical, haematological and virology results. Conclusion: Gammaplex achieved a very high concentration of serum IgG but was well-tolerated and effective in the treatment of ITP with a similar degree of efficacy to the pre-determined historical control group and the pre-set statistical criteria. Trial Registration ClinicalTrials.gov NCT00504075 Clinical Trials Registry India 000016 PMID:24892422

  19. First-line therapies for immune thrombocytopenic purpura: re-evaluating the need to treat.

    PubMed

    Rodeghiero, Francesco

    2008-02-01

    Immune thrombocytopenic purpura (ITP) can be challenging to both diagnose and treat: despite the ability to detect anti-platelet antibodies, the diagnosis of ITP remains one of exclusion. Management of ITP is similarly difficult as many therapies pose potential risks that may be worse than the disease. It has been generally agreed that bleeding - not platelet count - should be the rationale for treatment. Despite the absence of prospective, controlled studies, there is consensus that bleeding risks are significantly greater in patients with platelet counts <20 x 10(9)-30 x 10(9)/L, and therefore treatment is indicated for these patients; for those with platelet counts that are higher, but still <50 x 10(9)/L, treatment is also indicated if accompanied by substantial mucous membrane bleeding. The standard initial treatment for ITP is oral corticosteroids to increase platelet counts. Intravenous immunoglobulin or anti-D immunoglobulin can also increase platelet counts and are particularly useful for stimulating rapid platelet increases before planned procedures. Splenectomy, which produces a long-lasting response in a majority of patients, is still commonly used for those who do not have long-term responses to steroid therapy and it should remain the gold standard therapy. However, splenectomy is an invasive procedure with some patients relapsing even after several years. Very rare cases of life-threatening or lethal infections may also occur at any time after splenectomy and thus physicians and patients are increasingly reluctant to advise or agree to this treatment approach. Other treatments have been evaluated to prevent or delay splenectomy, including high-dose dexamethasone, intermittent anti-D immunoglobulin infusions, and rituximab. There have been few randomized, placebo-controlled studies of these approaches, and they cannot currently be recommended as their efficacy and safety remain unclear. Thrombopoietin receptor agonists are currently under clinical investigation for the treatment of ITP and may represent an alternative treatment option in the future. The criteria for treating ITP and the benefits and risks of therapies are discussed here. Ongoing and future studies will help define the best strategies for increasing platelet counts and reducing the risk of bleeding in ITP patients. PMID:18211569

  20. New advances in the treatment of adult chronic immune thrombocytopenic purpura: role of thrombopoietin receptor-stimulating agents

    PubMed Central

    Metjian, Ara; Abrams, Charles S

    2009-01-01

    Decades of basic science and clinical research have led to an increased understanding of the pathophysiology of immune thrombocytopenic purpura (ITP), the processes underlying thrombopoiesis, and the treatment of chronic ITP. Now, new agents are available to treat ITP in a nonimmunosuppressive fashion. Lessons learned from the clinical trials of recombinant human thrombopoietin (TPO) have led to the development of a novel class of compounds: nonimmunogenic agonists of the thrombopoietin receptor. Representing the first nonimmunosuppressive agents to treat chronic refractory ITP in decades, medications such as romiplostim and eltrombopag were recently approved by the US Food and Drug Administration. These new agents offer physicians a new tool for treating difficult cases of ITP in their medical armamentarium. Additional TPO mimetics are also being developed that show promise in vitro, and await future development. PMID:20054440

  1. Kinetics and sites of destruction of ¹¹¹In-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study

    Microsoft Academic Search

    A. Dup. Heyns; M. G. Loetter; P. N. Badenhorst; Felicity De Kock; H. Pieters; C. Herbst; O. R. van Reenen; H. Kotze; P. C. Minnaar

    1982-01-01

    Kinetics and quantification of the sites of destruction of ¹¹¹In-oxine-labeled autologous platelets were investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 +\\/- 9 X 10(9)\\/liter; platelets were separated by differential centrifugation and labeled with 5.6 +\\/- 2.5 MBq ¹¹¹In. Whole body and organ ¹¹¹In-platelet distribution was quantitated with a scintillation camera and a computer-assisted

  2. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura

    Microsoft Academic Search

    Roberto Stasi; Adalberto Pagano; Elisa Stipa; Sergio Amadori

    The role of rituximab, a chimeric monoclo- nal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic pur- pura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between

  3. Idiopathic Relapsing Thrombotic Thrombocytopenic Purpura with Persistent ADAMTS13 Inhibitor Activity Treated Sequentially with Plasmapheresis, Rituximab, Cyclophosphamide and Splenectomy

    PubMed Central

    Musa, Faisal; Baidas, Said

    2015-01-01

    We here describe a patient with an idiopathic thrombotic thrombocytopenic purpura (TTP) secondary to an ADAMTS13 inhibitor that continued to be dependent on plasmapheresis until the patient was treated with rituximab. TTP manifestations subsided with rituximab treatment in spite of a persistently low ADAMTS13 activity and continued a detectable inhibitor activity until the patient developed an intolerance to rituximab due to an allergic reaction when cyclophosphamide was added; this resulted in a normalization of ADAMTS13 activity and the disappearance of the inhibitor. Later, the patient developed an intolerance to rituximab due to a severe allergic reaction. Soon after stopping rituximab, the ADAMTS13 activity level dipped below 5% in addition to the appearance of the ADAMTS13 inhibitor. The patient had a splenectomy after rituximab and cyclophosphamide treatment; the medication was stopped based on several case reports of a complete remission of TTP after splenectomy. We believe that the reason TTP went into remission in our patient was because of rituximab treatment, in spite of both persistently low ADAMTS13 activity and a detectable inhibitor activity due to reducing the release of von Willebrand factor large multimers from the endothelial cells. We found that ADAMTS13 activity normalized and the inhibitor activity became undetectable when cyclophosphamide was added to rituximab. We suggest adding cyclophosphamide to rituximab for the treatment of patients with persistent ADAMTS13 inhibitors in order to prolong the remission period and lower the rate of relapse.

  4. Docetaxel-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome-related complex in a patient with metastatic prostate cancer?

    PubMed

    Shrestha, Anuj; Khosla, Pam; Wei, Yunfei

    2011-09-01

    A 63-year-old African American man was diagnosed with prostate cancer by biopsy for elevated prostrate-specific antigen. He was initially treated with radiation and then with intermittent androgen ablation because of biochemical relapse. He continued to have rising prostrate-specific antigen and he was thought to have hormone-resistant prostate cancer. So he received chemotherapy with docetaxel. He returned to the hospital within 3 days of the first cycle of treatment with fever, altered mental status, acute renal failure, anemia, and thrombocytopenia. He was started on empiric antibiotics but his cultures from most sites were negative. His platelets dropped from 119,000 to a nadir of 10,000 during hospital stay. Patient had microangiopathic hemolytic anemia suggested by elevated lactate dehydrogenase, decreased haptoglobin, increased indirect bilirubin, and schistocytes in peripheral smear. His coagulation profile was normal. A presumptive diagnosis of chemotherapy-related thrombotic thrombocytopenic purpura (TTP)-hemolytic uremic syndrome was made and patient was started on fresh frozen plasma infusion and hemodialysis for renal failure and steroids. Patient improved symptomatically, platelet count was stable, and lactate dehydrogenase was in a declining trend after 5 days of fresh frozen plasma infusion. The ADAMS TS-13 activity was 37% suggestive of chemotherapy-related TTP. Patient also had sickle cell beta thalassemia disease and glucose 6 phosphate dehydrogenase deficiency. Docetaxel, like some other vascular endothelial growth factor inhibiting chemotherapeutic drugs may cause TTP-hemolytic uremic syndrome. PMID:20592666

  5. Polymorphism and expression of macrophage migration inhibitory factor does not contribute to glucocorticoid resistance in idiopathic thrombocytopenic purpura.

    PubMed

    Lao, Wansheng; Xiang, Yang; Fang, Meiyun; Yang, Xifei

    2013-10-01

    Glucocorticoids (GCs) are considered the important drugs used in treatment of idiopathic thrombocytopenic purpura (ITP). However, about 10-30% patients with ITP develop GC resistance after standard treatment with GC. The macrophage migration inhibitory factor (MIF) has been shown to act as a counter-regulator of the anti-inflammatory and immunosuppressive effects of GCs on immune cells. In addition, MIF-173G/C polymorphism was associated with higher MIF expression both in vitro and in vivo. In this case-control study, we investigated the association of GC resistance with MIF polymorphism and expression. MIF mRNA expression was analyzed by semiquantitative real-time RT-PCR in GC-sensitive and GC-resistant ITP patients. MIF protein expression in serum was performed by ELISA. Genotyping for the MIF -173G/C polymorphism was analyzed by a Polymerase chain reaction Tm-shift genotyping method. We found no association of GC resistance and MIF mRNA and protein expression. According to sex, age, initial blood platelet count, and disease course, the patients were further subdivided into 8 groups, no statistical difference was found. In addition, we compared the distribution of the MIF -173G/C genotype and allele frequencies between the GC-sensitive ITP patients and the GC-resistant and found no statistical difference. The present study suggested that MIF polymorphism and expression does not contribute to GC resistance in ITP. PMID:24273891

  6. Resolution of immune thrombocytopenic purpura associated with extranodal B-cell lymphoma of the petroclival region after radiotherapy

    PubMed Central

    Watanabe, Takashi; Kurihara, Hideyuki; Magarisawa, Satoshi; Shimoda, Shigeru; Yoshida, Katsue; Ishiuchi, Shogo

    2010-01-01

    Background: Secondary immune thrombocytopenic purpura (ITP) associated with extranodal B-cell non-Hodgkin’s lymphoma (NHL) is extremely rare. The optimal management is not established. We report a first case of ITP in association with extranodal B-cell NHL originating in the lower petroclival region, successfully managed by local tumor control using conventional radiotherapy. Case Description: A 75-year-old man presented with a two-month history of hearing loss, hoarseness, and dysphagia. Neuroimaging revealed a large enhanced lesion in the left lower petroclival bone near the jugular foramen. Isolated unilateral parotid lymphadenopathy was also noted. Preoperative laboratory findings were normal, except for elevation of serum soluble interleukin-2 receptor level. A suboccipital craniotomy was performed and a biopsy sample was taken. Histological and immunohistochemical examination confirmed small B-cell lymphoma with plasmacytic differentiation. After initiation of radiotherapy, thrombocytopenia (24,000/µl) rapidly developed. Serological and bone marrow examination confirmed ITP. Prednisone was given at 1 mg/kg/day and radiation therapy was continued. After more than 32Gy, platelet count rapidly normalized. Radiotherapy to the tumor site achieved local tumor control and ITP was resolved. No evidence of recurrence and normal platelet count were confirmed at the two-year follow-up examination. Conclusion: Local control of the tumor was considered important in the resolution of secondary ITP in association with extranodal NHL of the skull base region. PMID:21170367

  7. In vitro megakaryocyte colony formation in patients with idiopathic thrombocytopenic purpura: differences between acute and chronic ITP.

    PubMed

    Abgrall, J F; el-Kassar, N; Berthou, C; Renard, I; Cauvin, J M; Le Pailleur, A; Autrand, C; Sensebe, L; Guern, G; Zilliken, P

    1992-01-01

    In vitro megakaryocyte colony formation from the bone marrow of patients with acute idiopathic thrombocytopenic purpura (ITP) or chronic ITP was compared using a plasma clot system. The number of megakaryocyte colony-forming units (CFU-Meg) was significantly higher (p less than 0.05) in acute ITP compared to chronic ITP (54.3 +/- 68.4 vs. 12.9 +/- 15.3/10(5) nonadherent mononuclear cells, mean +/- SD), and significantly lower (p less than 0.05) in chronic ITP compared to controls (12.9 +/- 15.3 vs. 22.8 +/- 15.9). A significant correlation was observed between platelet recovery 7 and 30 days after culture, and the number of CFU-Meg (r = 0.49 and 0.45, respectively, p less than 0.05). An inverse correlation was observed between platelet count at the time of culture and the number of Megs per colony (r = -0.48, p less than 0.05). These results indicated a difference between acute and chronic ITP in the ability to promote in vitro Meg colony formation and may suppose a different immune mechanism for thrombocytopenia in these two disorders. PMID:1552223

  8. A Case of Behçet's Disease with Pericarditis, Thrombotic Thrombocytopenic Purpura, Deep Vein Thrombosis and Coronary Artery Pseudo Aneurysm

    PubMed Central

    Kwon, Chang Mo; Lee, Seung Hyun; Kim, Jin Ho; Lee, Kyu Hyung; Kim, Hyun Do; Hong, Yeong Hoon

    2006-01-01

    Behçet's disease with concomitant thrombotic thrombocytopenic purpura (TTP), coronary artery stenosis and coronary artery pseudo aneurysm is rare. Here we report a case of Behçet's disease with several cardiovascular complications, namely: pericarditis, deep vein thrombosis (DVT), TTP, coronary artery stenosis, and a coronary artery pseudo aneurysm. A 37-year-old female presented with sudden dyspnea and syncope at our emergency room and underwent pericardiectomy and pericardial window formation for the diagnosis of cardiac tamponade with acute hemorrhagic pericarditis. Thereafter, TTP and DVT complicated her illness. After confirmation of Behçet's disease on the basis of a history of recurrent oral and genital ulcers and erythema nodosum, remission was achieved after treatment with methylprednisolone pulse therapy, colchicine, catheter directed thrombolysis and thrombectomy. However, whilst maintaining anticoagulation therapy, a newly developed pericardial aneurysmal dilatation was noted on follow-up radiologic evaluation. Further evaluation revealed right coronary artery stenosis and a left coronary artery pseudo aneurysm; these additional problems were treated with the nonsurgical insertion of an endovascular graft stent. At the time of writing three months later after stent insertion, the aneurysm has continued to regress and no additional complications have intervened with combined immunosuppressive therapy. PMID:16646566

  9. Idiopathic Relapsing Thrombotic Thrombocytopenic Purpura with Persistent ADAMTS13 Inhibitor Activity Treated Sequentially with Plasmapheresis, Rituximab, Cyclophosphamide and Splenectomy.

    PubMed

    Musa, Faisal; Baidas, Said

    2015-01-01

    We here describe a patient with an idiopathic thrombotic thrombocytopenic purpura (TTP) secondary to an ADAMTS13 inhibitor that continued to be dependent on plasmapheresis until the patient was treated with rituximab. TTP manifestations subsided with rituximab treatment in spite of a persistently low ADAMTS13 activity and continued a detectable inhibitor activity until the patient developed an intolerance to rituximab due to an allergic reaction when cyclophosphamide was added; this resulted in a normalization of ADAMTS13 activity and the disappearance of the inhibitor. Later, the patient developed an intolerance to rituximab due to a severe allergic reaction. Soon after stopping rituximab, the ADAMTS13 activity level dipped below 5% in addition to the appearance of the ADAMTS13 inhibitor. The patient had a splenectomy after rituximab and cyclophosphamide treatment; the medication was stopped based on several case reports of a complete remission of TTP after splenectomy. We believe that the reason TTP went into remission in our patient was because of rituximab treatment, in spite of both persistently low ADAMTS13 activity and a detectable inhibitor activity due to reducing the release of von Willebrand factor large multimers from the endothelial cells. We found that ADAMTS13 activity normalized and the inhibitor activity became undetectable when cyclophosphamide was added to rituximab. We suggest adding cyclophosphamide to rituximab for the treatment of patients with persistent ADAMTS13 inhibitors in order to prolong the remission period and lower the rate of relapse. PMID:26034479

  10. The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs.

    PubMed

    Schaller, Monica; Vogel, Monique; Kentouche, Karim; Lämmle, Bernhard; Kremer Hovinga, Johanna A

    2014-11-27

    Acquired thrombotic thrombocytopenic purpura (TTP) is the consequence of a severe ADAMTS13 deficiency resulting from autoantibodies inhibiting ADAMTS13 or accelerating its clearance. Despite the success of plasma exchange the risk of relapse is high. From 2 patients (A and B), splenectomized for recurrent episodes of acquired TTP, the splenic B-cell response against ADAMTS13 was characterized through generation of human monoclonal anti-ADAMTS13 autoantibodies (mAbs) by cloning an immunoglobulin G (IgG)4?- and IgG4?-Fab library using phage display technology and by Epstein-Barr virus transformation of switched memory B cells (CD19+/CD27+/IgG+). Sequence analysis of the anti-ADAMTS13 IgGs of both patients revealed that the VH gene use was limited in our patients to VH1-3 (55%), VH1-69 (17%), VH3-30 (7%), and VH4-28 (21%) and contained 8 unique and thus far not reported heavy-chain complementarity determining region 3 motifs, of which 4 were shared by the 2 patients. The discovery of several highly similar anti-ADAMTS13 autoantibodies in 2 unrelated TTP patients suggests that the autoimmune response is antigen driven, because the probability that such similar immunoglobulin rearrangements happen by chance is very low (< 10(-9)). PMID:25261198

  11. Efficacy and Safety of Rituximab for Refractory and Relapsing Thrombotic Thrombocytopenic Purpura: A Cohort of 10 Cases

    PubMed Central

    Omri, Halima El; Taha, Ruba Y; Gamil, Amna; Ibrahim, Firyal; Sabah, Hisham Al; Mahmoud, Zeinab O; Pittari, Gianfranco; HIjji, Ibrahim Al; Yassin, Mohamed A

    2015-01-01

    OBJECTIVE Idiopathic thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder mediated by autoantibodies directed against ADAMTS13. This provides a rationale for the use of rituximab in this disorder. We report our experience and the outcome of 10 cases of TTP (9 refractory and 1 relapsing) successfully treated with rituximab in combination with plasma exchange (PE) and other immunosuppressive treatments. METHODS The diagnosis of TTP was based on clinical criteria and supported by severe deficiency of ADAMTS13 activity and presence of inhibitors in seven cases. Rituximab was started after a median of 18.6 sessions of PE (range: 5–35) at the dose of 375 mg/m2/week for 4–8 weeks. RESULTS Complete remission was achieved in all patients after a median time of 14.4 days of the first dose (range: 6–30). After a median follow-up of 30 months (range: 8–78), eight patients were still in remission and two developed multiple relapses, treated again with the same therapy, and achieved complete responses; they are alive, and in complete remission after a follow-up of 12 and 16 months. CONCLUSION Rituximab appears to be a safe and effective therapy for refractory and relapsing TTP. However, longer follow-up is recommended to assess relapse and detect possible long-term side effects of this therapy.

  12. [Thymic mucosa-associated lymphoid tissue (MALT) lymphoma developing during long-term follow-up for Sjögren's syndrome and idiopathic thrombocytopenic purpura;report of a case].

    PubMed

    Sawada, Takahiro; Machino, Ryusuke; Ishii, Mitsuhisa; Takeji, Miyuki; Maeda, Toshiharu

    2013-11-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of lymphoma that arises in small CD20-positive lymphocytes. We encountered a case of thymic MALT lymphoma treated with surgical intervention during long-term follow-up for Sjögren's syndrome and idiopathic thrombocytopenic purpura (ITP). Although symptomatic remission of Sjögren's syndrome and ITP had already been achieved, the levels of anti-SSA and anti-SSB antibodies remained high. Chronic stimulation by these antibodies may contribute to the development of MALT lymphoma. A careful follow-up may be indicated for this case with a complex immunological background. PMID:24322322

  13. Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

    PubMed Central

    Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

    2012-01-01

    Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

  14. Thrombotic thrombocytopenic purpura in a patient with rapidly progressive glomerulonephritis with both anti-glomerular basement membrane antibodies and myeloperoxidase anti-neutrophil cytoplasmic antibodies

    Microsoft Academic Search

    Hitoshi Watanabe; Wataru Kitagawa; Keisuke Suzuki; Masabumi Yoshino; Ryuhei Aoyama; Naoto Miura; Kazuhiro Nishikawa; Hirokazu Imai

    2010-01-01

    A 61-year-old Japanese woman with rapidly progressive glomerulonephritis exhibited both anti-glomerular basement membrane\\u000a (GBM) antibodies (920 EU) and myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA; 66 EU). Multiple plasma exchanges\\u000a with fresh frozen plasma preceded by 500 mg\\/day intravenous methylprednisolone and 30 mg\\/day oral prednisolone decreased anti-GBM\\u000a antibody and MPO-ANCA antibody titers to 106 EU and below 10 EU (normal ranges), respectively. Thrombotic thrombocytopenic\\u000a purpura (TTP) manifests itself

  15. T suppressor activated lymphocytes (CD8+/DR+) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura.

    PubMed

    Benedetti, F; de Sabata, D; Perona, G

    1994-03-01

    Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disease, characterized by isolated thrombocytopenia and the absence of megakaryocytes in bone marrow. Recent studies suggest that this syndrome is due to diverse etiologies. Humoral or cellular mediated suppression has been alternately demonstrated using an in vitro colony assay for megakaryocytic progenitor cells (colony forming units megakaryocyte, [CFU-meg]). We studied a patient affected by AATP, who was not responsive to conventional therapy, but did respond to antilymphocyte globulin. The immunological characterization of marrow lymphocytes showed a marked increase of T activated suppressor cells (CD8+/DR+). Low density bone marrow mononuclear nonadherent cells (MNAC) from the patient, either in aplastic phase or in remission phase, were plated in plasma clot either directly or after T cell depletion (T-dep MNACs). Co-cultures with normal marrow cells were performed using either T lymphocytes from a normal volunteer donor or patient T lymphocytes. In some experiments we added autologous serum instead of fetal calf serum (FCS). In standard conditions, we observed increased colony formation, which was more evident in remission phase and especially significant after T cell depletion. The T lymphocytes from patient marrow did not modify the number of CFU-meg when co-cultured with allogeneic cells. These results indicate that an immune-mediated mechanism could be responsible for this case of AATP, and that the T cell subset CD8+/DR+ is capable of exerting suppression on megakaryocyte differentiation. This suppressive effect seems restricted to patient cells, suggesting a specific auto-sensitization. PMID:8199563

  16. Comparison of anti-D immunoglobulin, methylprednisolone, or intravenous immunoglobulin therapy in newly diagnosed pediatric immune thrombocytopenic purpura.

    PubMed

    Celik, Muhittin; Bulbul, Ali; Aydogan, Gönül; Tugcu, Deniz; Can, Emrah; Uslu, Sinan; Dursun, Mesut

    2013-02-01

    This study aimed to evaluate the efficacy, cost, and effects of anti-D immunoglobulin (anti-D Ig), methylprednisolone, or intravenous immunoglobulin (IVIG) therapy on the development of chronic disease in children who are Rh-positive with diagnosed immune thrombocytopenic purpura (ITP). Children with newly diagnosed ITP and platelet count <20,000/mm(3) were prospectively randomized to treatment with anti-D Ig (50 ?g/kg), methylprednisolone (2 mg/kg/day), or IVIG (0.4 g/kg/day, 5 days). Sixty children with a mean age of 6.7 years were divided into three equal groups. No difference was observed between platelet counts before treatment and on day 3 of treatment. However, platelet counts at day 7 were lower in the methylprednisolone group than in the IVIG group (P = 0.03). In the anti-D Ig group, hemoglobin and hematocrit levels were significantly lower at the end of treatment (P < 0.05). Chronic ITP developed in 30% of the anti-D Ig group, 35% of the methylprednisolone group, and 25% of the IVIG group, but no significant difference was noted among the groups. The cost analysis revealed that the mean cost of IVIG was 7.4 times higher than anti-D Ig and 10.9 times higher than methylprednisolone. In the treatment of ITP in childhood, one 50 ?g/kg dose of anti-D Ig has similar effects to IVIG and methylprednisolone. Among patients who were treated with anti-D Ig, serious anemia was not observed, and the cost of treatment was less than that of IVIG treatment. PMID:22956408

  17. Fatal outcome of infection by dengue 4 in a patient with thrombocytopenic purpura as a comorbid condition in Brazil.

    PubMed

    Amâncio, Frederico Figueiredo; Pereira, Maira Alves; Iani, Felipe Campos de Melo; D'anunciação, Lorena; de Almeida, Jorge Luís Carvalho; Soares, Janer Aparecida Silveira; Ferraz, Marcela Lencine; Vale, Thiago Cardoso; Lambertucci, José Roberto; Carneiro, Mariângela

    2014-01-01

    Dengue is currently a major public-health problem. Dengue virus (DENV) is classified into four distinct serotypes, DENV 1-4. After 28 years of absence, DENV-4 was again detected in Brazil in 2010 in Roraima State, and one year later, the virus was identified in the northern Brazilian states of Amazonas and Pará, followed by Rio de Janeiro and São Paulo. In Minas Gerais, the first confirmed case of DENV-4 occurred in the municipality of Frutal in 2011 and has now been isolated from a growing number of patients. Although DENV-2 is associated with the highest risk of severe forms of the disease and death due to the infection, DENV-4 has also been associated with severe forms of the disease and an increasing risk of hemorrhagic manifestations. Herein, the first fatal case of confirmed DENV-4 in Brazil is reported. The patient was an 11-year-old girl from the municipality of Montes Claros in northern Minas Gerais State, Brazil. She had idiopathic thrombocytopenic purpura as a comorbid condition and presented with a fulminant course of infection, leading to death due to hemorrhagic complications. Diagnosis was confirmed by detection of Dengue-specific antibodies using IgM capture enzyme-linked immunosorbent assay and semi-nested RT-PCR. Primary care physicians and other health-care providers should bear in mind that DENV-4 can also result in severe forms of the disease and lead to hemorrhagic complications and death, mainly when dengue infection is associated with coexisting conditions. PMID:24879007

  18. Kinetics and sites of destruction of /sup 111/In-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study

    SciTech Connect

    Heyns, A.D.; Loetter, M.G.; Badenhorst, P.N.; de Kock, F.; Pieters, H.; Herbst, C.; van Reenen, O.R.; Kotze, H.; Minnaar, P.C.

    1982-04-01

    Kinetics and quantification of the sites of destruction of /sup 111/In-oxine-labeled autologous platelets were investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 +/- 9 X 10(9)/liter; platelets were separated by differential centrifugation and labeled with 5.6 +/- 2.5 MBq /sup 111/In. Whole body and organ /sup 111/In-platelet distribution was quantitated with a scintillation camera and a computer-assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ /sup 111/In-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49.5 +/- 29.6 hr and the survival curves were exponential. Equilibrium percentage organ /sup 111/In-radioactivity was (normal values in parentheses): spleen 33.7 +/- 8.8 (31.1 +/- 10.2); liver 16.1 +/- 9.5 (13.1 +/- 1.3); thorax 22.8 +/- 3.7 (28.2 +/- 5.6). Percentage organ /sup 111/In-activity at the time when labeled platelets had disappeared from the circulation was: spleen 44.5 +/- 16.4 (40 +/- 16); liver 16.0 +/- 11.5 (32.4 +/- 7.2); thorax 19.7 +/- 6.0 (17.7 +/- 10.3). Thorax activity corresponds to bone marrow radioactivity. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration, two mainly hepatic sequestration, and three diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of /sup 111/In-platelet sequestration was not predictive of response of glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative /sup 111/In-labeled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.U

  19. Rituximab therapy for chonic and refractory immune thrombocytopenic purpura: a long-term follow-up analysis

    PubMed Central

    Garcia-Chavez, Jaime; Montiel-Cervantes, Laura; Esparza, Miriam García-Ruiz; Vela-Ojeda, Jorge

    2007-01-01

    The aim of this study was to evaluate the long-term response to rituximab in patients with chronic and refractory immune thrombocytopenic purpura (ITP). Adults with ITP fail to respond to conventional therapies in almost 30% of cases, developing a refractory disease. Rituximab has been successfully used in these patients. We used rituximab at 375 mg/m2, IV, weekly for a total of four doses in 18 adult patients. Complete remission (CR) was considered if the platelet count was >100?×?109/l, partial remission (PR) if platelets were >50?×?109/l, minimal response (MR) if the platelet count was >30?×?109/l and <50?×?109/l, and no response if platelet count remained unchanged. Response was classified as sustained (SR) when it was stable for a minimum of 6 months. Median age was 43.5 years (range, 17 to 70). Median platelet count at baseline was 12.5?×?109/l (range, 3.0 to 26.3). CR was achieved in five patients (28%), PR in five (28%), MR in four (22%), and two patients were classified as therapeutic failures (11%). Two additional patients were lost to follow-up. The median time between rituximab therapy and response was 14 weeks (range, 4 to 32). SR was achieved in 12 patients (67%). There were no severe adverse events during rituximab therapy. During follow-up (median, 26 months; range, 12 to 59), no other immunosuppressive drugs were used. In conclusion, rituximab therapy is effective and safe in adult patients with chronic and refractory ITP. Overall response rate achieved is high, long term, and with no risk of adverse events. PMID:17874322

  20. Rituximab therapy for thrombotic thrombocytopenic purpura: A proposed study of the Transfusion Medicine\\/Hemostasis Clinical Trials Network with a systematic review of rituximab therapy for immune-mediated disorders

    Microsoft Academic Search

    James N. George; Robert D. Woodson; Joseph E. Kiss; Kiarash Kojouri; Sara K. Vesely

    2006-01-01

    The rationale for immunosuppressive therapy of thrombotic thrombocytopenic purpura (TTP) was estab- lished by observations that TTP may be caused by autoantibodies to ADAMTS13. Patients with high-titer autoantibodies to ADAMTS13 may have a higher mortality, and survivors may require prolonged plasma exchange therapy in spite of adjunctive glucocorticoid treatment. More intensive immunosuppressive therapy with rituximab may provide benefit for many

  1. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report

    PubMed Central

    2012-01-01

    Background The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS) and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case presentation We report an uncommon case of a white 53?year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Conclusion Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient. PMID:23256875

  2. A single-institution, 20-year prospective experience with an affordable Fc-receptor blockade method to treat patients with chronic, refractory autoimmune thrombocytopenic purpura.

    PubMed

    Estrada-Gómez, Roberto; Vargas-Castro, Olga; Oropeza-Borges, Mabel; González-Carrillo, Martha L; Pérez-Romano, Beatriz; Ruiz-Argüelles, Guillermo J

    2007-01-01

    In a 20-year period in a single institution, 34 patients with chronic, refractory autoimmune thrombocytopenic purpura were prospectively treated with ex vivo anti-D opsonized autologous red blood cells. All patients had received previous treatment with steroids and/or immunosuppressive agents, and 11 had been splenectomized. Twenty one patients had an increase in the platelet count; in five cases, the increase was more than 50 x 10(9)/L platelets and in 16 the increase was more than 100 x 10(9)/L platelets. Early responses were observed in 20 patients and late responses in seven, whereas seven patients (20%) did not respond at all. Nine of the 20 individuals who achieved an ER had a subsequent drop in the platelet count; however, only three had a drop below 50 x 10(9)/L. When last censored, of the 34 patients, 24 (70%) had a platelet count above 50 x 10(9)/L. The 84-month thrombocytopenia-free (over 50 x 10(9)/L platelets) status of the whole group is 70%, whereas the 84-month complete remission (over 100 x 10(9)/L platelets) status of the whole group is 50%. It is concluded that the use of ex vivo anti-D opsonized red blood cells may represent another, substantially cheaper treatment of patients with chronic, refractory, autoimmune thrombocytopenic purpura. PMID:18402333

  3. The mechanisms of action of intravenous immunoglobulin and polyclonal anti-d immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know?

    PubMed

    Crow, Andrew R; Lazarus, Alan H

    2008-04-01

    Intravenous immunoglobulin (IVIg) has been used for more than 25 years to treat an ever-increasing number of autoimmune diseases including immune thrombocytopenic purpura. Although the exact mechanism of action of IVIg has remained elusive, many theories have been postulated, including mononuclear phagocytic system blockade/inhibition, autoantibody neutralization by anti-idiotype antibodies, pathogenic autoantibody clearance due to competitive inhibition of the neonatal immunoglobulin Fc receptor, cytokine modulation, complement neutralization, and immune complex formation leading to dendritic cell priming. Polyclonal anti-D immunoglobulin is a polyclonal IVIg product enriched for antibodies directed to the RhD antigen on red blood cells and that has also been successfully used to treat immune thrombocytopenia in RhD(+) patients. The primary theory to explain polyclonal anti-D immunoglobulin function has classically been mononuclear phagocytic system blockade, although modulation of Fcgamma receptor expression and/or immunomodulation may also play a role. Work using a murine model of immune thrombocytopenic purpura to further our understanding of the mechanism of action of these 2 therapeutic agents is a focus of this article. PMID:18353251

  4. [Recent progress of study on mechanism of immune thrombocytopenic purpura and its clinical treatment - review].

    PubMed

    Lu, Xue-Chun; Zhu, Hong-Li; Yao, Shan-Qian

    2008-10-01

    Immune thrombocytopenia purpura (ITP) is a disorder mediated by antiplatelet antibodies and characterized by accelerated destruction of platelets and impaired platelet production. The mainstay therapies for ITP have included corticosteroids, the immune globulin intravenous immunoglobulin and IV anti-D (monoclonal antibodies against the D antigen of the Rh system), vinblastine or a monoclonal anti-CD20 antibody that transiently depletes CD20(+) B cells, danazol, cyclophosphamide and even splenectomy to refractory one. Most of ITP patients responded to those treatment, while more than 30% of whom may relapse sooner or later. The recombinant forms of human TPO were discontinued from human use in clinic because recipients of these agents developed significant thrombocytopenia secondary to production of neutralizing antibodies that cross-reacted with endogenous TPO. All above mentioned treatments have side effects and severe infection may arise post splenectomy. The more powerful treatment with less side effects are needed. There are two TPO receptor agonist, AMG531 and Eltrompobag, have approved in Europe for the treatment of ITP. Both of them can improve the differentiation of megakaryocyte and platelets production. Combination treatment including pancytoprotector shows good effect in the treatment of refractory and relapsed ITP in China. Altogether, individual treatment of ITP is the contemporary trend in both clinical and preclinical practice. In this review the pathogenesis of ITP and its clinical therapies were reviewed, the individual regiments for treating ITP patients were discussed. PMID:18928635

  5. Acquired amegakaryocytic thrombocytopenic purpura (AATP): a study of autologous megakaryocyte progenitors and the effect of patients plasma on normal marrow megakaryocyte colony formation.

    PubMed

    Podolak-Dawidziak, M

    1990-01-01

    Megakaryocyte progenitors (Colony Forming Unit-Megakaryocyte, CFU-Mk) and the effect of plasma on megakaryocyte colony formation in normal human marrow (Plasma Factor Index-Megakaryocyte, PFI-Mk) were studied in six patients with acquired amegakaryocytic thrombocytopenic purpura (AATP) and in ten normal subjects. Assay was based on the method of Messner. In one AATP marrow culture four CFU-Mk were found, in the other two a single CFU-Mk were present, and in the remaining three samples no megakaryocyte colonies were observed. PFI-Mk in AATP patients was significantly higher than in normal subjects. No correlation was found between PFI-Mk and platelet count in either group. The results of this study indicate the presence of an intrinsic defect at the level of CFU-Mk in AATP marrow. PFI-Mk in AATP patients relate to changes in marrow megakaryocyte number rather than to peripheral blood platelet count. PMID:1697840

  6. Successful treatment of sepsis-induced disseminated intravascular coagulation in a patient with idiopathic thrombocytopenic purpura using recombinant human soluble thrombomodulin.

    PubMed

    Koga, Tomohiro; Inoue, Daisuke; Okada, Akitomo; Aramaki, Toshiyuki; Yamasaki, Satoshi; Nakashima, Munetoshi; Kawakami, Atsushi; Eguchi, Katsumi

    2011-12-01

    Disseminated intravascular coagulation (DIC) may complicate a variety of disorders that contribute to mortality, particularly those related to bleeding. It is therefore very difficult to manage DIC in patients with known bleeding disorders. We treated a 62-year-old woman with idiopathic thrombocytopenic purpura (ITP) complicated with sepsis-induced DIC. She had been diagnosed with ITP 8 months prior to admission. Laboratory tests showed an elevation of d-dimer and endotoxin, while pyelonephritis was shown by abdominal computed tomography. Escherichia coli was detected by blood culture. Based on these findings, the patient was diagnosed with sepsis-induced DIC due to urinary tract infection. Thrombocytopenia was refractory despite the use of antibiotics and platelet transfusion, but it was promptly improved in response to recombinant human soluble thrombomodulin (rTM). We suggest that rTM provides a new therapeutic strategy for DIC patients with high hemorrhagic risk. PMID:21240494

  7. Association of CD4+CD25+FoxP3+ regulatory T cells with natural course of childhood chronic immune thrombocytopenic purpura

    PubMed Central

    Son, Bo Ra

    2015-01-01

    Purpose The purpose of this study was to determine the frequency of CD4+CD25+FoxP3+ regulatory T cells (Treg) in the peripheral blood of patients with childhood chronic immune thrombocytopenic purpura (ITP) exhibiting thrombocytopenia and spontaneous remission. The findings of this study indicate the possibility of predicting spontaneous recovery and pathogenesis of childhood chronic ITP. Methods Eleven children with chronic ITP (seven thrombocytopenic and four spontaneous remission cases; mean age, 8.8 years; range, 1.7-14.9 years) were enrolled in this study. Five healthy children and eight healthy adults were included as controls. The frequency of Treg was evaluated by flow cytometry in the peripheral blood. Results In this study, four patients (36%) achieved spontaneous remission within 2.8 years (mean year; range, 1.0-4.4 years). The frequency of Treg was significantly lower in patients with persisting thrombocytopenia (0.13%±0.09%, P<0.05), than that in the patients with spontaneous remission (0.30%±0.02%), healthy adults controls (0.55%±0.44%), and healthy children controls (0.46%±0.26%). A significantly positive correlation was found between the frequency of Treg and the platelet count in children. Conclusion These data suggest that a lower frequency of Treg contributes to the breakdown of self-tolerance, and may form the basis for future development of specific immunomodulatory therapies. Furthermore, Treg frequency has prognostic implication toward the natural course and long-term outcomes of childhood chronic ITP.

  8. Comparison of intravenous immune globulin and high dose anti-D immune globulin as initial therapy for childhood immune thrombocytopenic purpura.

    PubMed

    Kane, Ian; Ragucci, Dominic; Shatat, Ibrahim F; Bussel, James; Kalpatthi, Ram

    2010-04-01

    This report documents our experience with intravenous immune globulin (IVIG) (1 g/kg, iv) and high-dose, anti-D immune globulin (anti-D) (75 microg/kg) as initial treatment for childhood immune thrombocytopenic purpura (ITP). The medical records of children diagnosed with ITP at a single institution between January 2003 and May 2008 were retrospectively reviewed. Participants received either IVIG or high-dose anti-D immune globulin as their initial treatment for ITP. For the 53 patients included for analysis, there was no statistical difference in efficacy between each group; however, patients who received anti-D experienced a higher rate of adverse drug reactions (ADRs), particularly chills and rigours, and 2 of 24 patients in the anti-D group developed severe anaemia requiring medical intervention. Patients who presented with mucosal bleeding had higher rates of treatment failure (32%) compared to those who presented with dry purpura (6%), regardless of treatment. Both IVIG and high-dose anti-D are effective first-line therapies for childhood ITP. However, we observed increased ADRs in the high-dose anti-D group in contrast to previously published reports. Further studies are needed to evaluate safety and premedications for high-dose anti-D and to determine the utility of using the presence of mucosal bleeding to predict treatment failure. PMID:20096011

  9. Acquired amegakaryocytic thrombocytopenic purpura.

    PubMed

    Agarwal, Neeraj; Spahr, Joseph E; Werner, Theresa L; Newton, David L; Rodgers, George M

    2006-02-01

    Acquired amegakaryocytic thrombocytopenia is an unusual hematologic disorder characterized by thrombocytopenia in association with markedly diminished bone marrow megakaryocytes. We report a case that responded to treatment with cyclosporine but not to IL-11. The bone marrow biopsy, repeated after resolution of thrombocytopenia, showed normal number of megakaryocytes. PMID:16432869

  10. Thrombotic Thrombocytopenic Purpura

    MedlinePLUS

    ... may sometimes hear it referred to as TTP–HUS. HUS, or hemolytic-uremic syndrome, is a disorder that ... Kidney problems also tend to be worse in HUS. Although some researchers think TTP and HUS are ...

  11. Thrombotic thrombocytopenic purpura

    MedlinePLUS

    Plasma exchange (plasmapheresis plus infusion of donor plasma) is used to remove the antibodies that are affecting clotting from the blood. It also replace the missing enzyme. First, you will have ...

  12. Total Hip Arthroplasty for Rapidly Destructive Coxarthrosis in a Patient with Severe Platelet Deficiency due to Liver Cirrhosis and Immune Thrombocytopenic Purpura

    PubMed Central

    Hama, Shunpei; Inori, Fumiaki; Momose, Dai; Konishi, Sadahiko

    2015-01-01

    Rapidly destructive coxarthrosis (RDC) causes rapid and extreme destruction of the hip joint, which was reported by Postel and Kerboull. RDC is commonly unilateral and occurs mostly in elderly women. Immune thrombocytopenic purpura (ITP) is characterized by a low platelet count that is the result of both immune-mediated platelet destruction and suppression of platelet production. In patients with ITP undergoing surgery, bleeding associated with a low preoperative platelet count can lead to unsuccessful outcomes. To the best of our knowledge, there has been only one report describing total hip arthroplasty (THA) for patients with ITP and there have been no reports of THA for RDC with a very low platelet count due to liver cirrhosis (LC) and ITP. We report the case of a patient who had right RDC and a very low platelet count due to LC and ITP in whom THA was successfully performed. Furthermore, this case was also unique in that her platelet count increased after THA. THA for right RDC might resolve ITP by relieving inflammation of the right hip since her platelet count recovered after THA.

  13. Low-dose autologous in vitro opsonized erythrocytes. Radioimmune method and autologous opsonized erythrocytes for refractory autoimmune thrombocytopenic purpura in adults

    SciTech Connect

    Ambriz, R.; Munoz, R.; Pizzuto, J.; Quintanar, E.; Morales, M.; Aviles, A.

    1987-01-01

    Adult patients with chronic autoimmune thrombocytopenic purpura (ATP), which proved refractory to various treatments, received a single dose of autologous in vitro opsonized erythrocytes with 100 micrograms of anti-D IgG. In 1983, 30 of these patients were treated with autologous erythrocytes that had been opsonized and labeled with 25 mCi (740 MBq) of technetium Tc 99m; this treatment was designated as the radioimmune method. Favorable responses were noted in 36% of patients so treated. In 1985, another group of 16 patients with refractory ATP received therapy with autologous opsonized erythrocytes (AOPE) and 55% of these patients showed favorable responses. Five (17%) of the patients treated using the radioimmune method attained a complete, long-term (greater than 35 months) remission of their ATP, and five (31%) of the patients treated using AOPE remained in complete remission over 270 days after cessation of therapy. Major complications were not seen. We concluded that the interaction of macrophages with low-dose AOPE is a successful therapeutic approach in ATP refractory to standard treatment.

  14. Total Hip Arthroplasty for Rapidly Destructive Coxarthrosis in a Patient with Severe Platelet Deficiency due to Liver Cirrhosis and Immune Thrombocytopenic Purpura.

    PubMed

    Hama, Shunpei; Inori, Fumiaki; Momose, Dai; Konishi, Sadahiko

    2015-01-01

    Rapidly destructive coxarthrosis (RDC) causes rapid and extreme destruction of the hip joint, which was reported by Postel and Kerboull. RDC is commonly unilateral and occurs mostly in elderly women. Immune thrombocytopenic purpura (ITP) is characterized by a low platelet count that is the result of both immune-mediated platelet destruction and suppression of platelet production. In patients with ITP undergoing surgery, bleeding associated with a low preoperative platelet count can lead to unsuccessful outcomes. To the best of our knowledge, there has been only one report describing total hip arthroplasty (THA) for patients with ITP and there have been no reports of THA for RDC with a very low platelet count due to liver cirrhosis (LC) and ITP. We report the case of a patient who had right RDC and a very low platelet count due to LC and ITP in whom THA was successfully performed. Furthermore, this case was also unique in that her platelet count increased after THA. THA for right RDC might resolve ITP by relieving inflammation of the right hip since her platelet count recovered after THA. PMID:26064742

  15. Anti-D (WinRho SD) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production.

    PubMed

    Semple, J W; Allen, D; Rutherford, M; Woloski, M; David, M; Wakefield, C; Butchart, S; Freedman, J; Blanchette, V

    2002-03-01

    Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 microg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral blood samples from the first and third cycles were assessed for cytokine levels at pre-treatment, 3 hr, 1 day, and 8 days post-treatment. Results showed that platelet counts significantly increased in all the children by day 8 post-treatment. Analysis of serum by ELISA showed that there was a significant but transient rise in both pro- and anti-inflammatory cytokine/chemokine levels (e.g., IL1RA, IL6, GM-CSF, MCP-1 alpha, TNF-alpha and MCP-1) by 3 hr post-treatment in both cycles which returned to baseline levels by 8 days post-treatment. These results suggest that anti-D administration may initially activate the RES in the form of cytokine/chemokine secretion, which is subsequently followed by an increase in platelet counts. It is possible that the induced cytokine/chemokine storm may have an effect on several physiological processes such as those mediating either adverse effects or potentially RES phagocytic activity. PMID:11891813

  16. Lack of impact of cytotoxic T-lymphocyte antigen 4 gene exon 1 polymorphism on susceptibility to or clinical course of egyptian childhood immune thrombocytopenic purpura.

    PubMed

    Radwan, Eman Roshdy; Goda, Rania L M

    2015-05-01

    Dysfunctional T-lymphocyte immunity plays an important role in the pathophysiology of immune thrombocytopenic purpura (ITP). Cytotoxic T-lymphocyte antigen 4 (CTLA-4)-a surface marker expressed on T regulatory cells and activated T lymphocytes-is a negative modulator of T-cell responses. Polymorphisms of the CTLA-4 may alter the level of antigen expression and hence may influence immune regulation. The study aimed to evaluate the possible contribution of CTLA-4 exon 1 49 A>G polymorphism to the pathogenesis of ITP and its relation to age of disease onset, clinical course, and response to therapy. Genotyping of CTLA-4 exon 1 49 A>G was performed in 100 pediatric patients with ITP and 259 healthy individuals by polymerase chain reaction-restricted fragment length polymorphism. No significant differences existed in genotype or allele distributions between patients and controls for the studied polymorphism. Comparable genotypes and allele frequencies were obtained between the 2 groups after their stratification by age of disease onset, clinical course, or response to therapy. In conclusion, CTLA-4 exon 1 49 A>G polymorphism is not associated with susceptibility to ITP in the Egyptian population; neither it affects the clinical picture of the disease. PMID:24023266

  17. Rozrolimupab, symphobodies against rhesus D, for the potential prevention of hemolytic disease of the newborn and the treatment of idiopathic thrombocytopenic purpura.

    PubMed

    Stasi, Roberto

    2010-12-01

    Currently under codevelopment by Symphogen and Swedish Orphan Biovitrum, rozrolimupab is the first in a new class of recombinant polyclonal antibodies, known as symphobodies, produced using a proprietary technology from Symphogen. Rozrolimupab is being investigated for the prevention of hemolytic disease of the fetus and newborn (HDFN) and for the treatment of idiopathic thrombocytopenic purpura (ITP). Rozrolimupab comprises 25 genetically unique IgG1 antibodies, all of which are specific for the rhesus D (RhD) erythrocyte protein. In preclinical studies, rozrolimupab demonstrated binding to erythrocytes that was comparable with that of two plasma-derived anti-D Ig preparations. In a phase I clinical trial in healthy male volunteers, treatment with rozrolimupab was not associated with serious adverse events. In a phase II clinical trial of rozrolimupab in healthy, male, RhD-negative volunteers, rozrolimupab dose-dependently cleared RhD-positive erythrocytes from the circulation. Phase II clinical trials in ITP and HDFN are currently ongoing. Phase III clinical trials are necessary to establish the efficacy and safety profile of rozrolimupab compared with standard plasma-derived anti-D Ig preparations. PMID:21154165

  18. Metastatic Breast Cancer with Extensive Osseous Metastasis Presenting with Symptomatic Immune Thrombocytopenic Purpura and Anemia: A Case Report and Review of the Literature

    PubMed Central

    Niu, Jiaxin; Goldin, Teresa; Markman, Maurie; Kundranda, Madappa N.

    2015-01-01

    Background Immune thrombocytopenic purpura (ITP) is a rare acquired bleeding disorder with an estimated incidence of 1 in 10,000 people in the general population. The association of ITP with breast cancer is an even rarer entity with very limited reports in the English literature. Case Presentation We report a case of a 51-year-old female with no significant past medical history who presented with sudden onset of malaise, syncope, gingival bleed and epistaxis. She was found to have severe thrombocytopenia (platelet count 6,000/?l) and anemia (hemoglobin 7.2 g/dl). Her workup led to the diagnosis of metastatic ductal breast cancer with extensive bone metastasis. Bone marrow biopsy demonstrated myelophthisis which was initially thought to be consistent with her presentation of thrombocytopenia and anemia. Therefore, the patient was started on hormonal therapy for the treatment of her metastatic breast cancer. After 3 months of therapy, she did not improve and developed severe mucosal bleeding. Her clinical presentation was suspicious for ITP and immune-mediated anemia, and hence she was started on steroids and intravenous immunoglobulin. The patient had a dramatic response to therapy with normalization of her platelet count and hemoglobin within 2 weeks. Conclusion To our knowledge, this is the first reported case of metastatic breast cancer presenting with symptomatic ITP and anemia, and both symptoms are postulated to be immune-mediated. PMID:26120311

  19. Progressive preleukemia presenting amegakaryocytic thrombocytopenic purpura: association of the 5q- syndrome with a decreased megakaryocytic colony formation and a defective production of Meg-CSF.

    PubMed

    Geissler, D; Thaler, J; Konwalinka, G; Peschel, C

    1987-01-01

    The authors present a patient with the typical clinical picture of an acquired amegakaryocytic thrombocytopenic purpura. After 16 months of observation, the patient developed acute myelomonocytic leukemia. During the preleukemic phase and after progression to overt leukemia, serial in-vitro analyses of megakaryocytic, granulocytic, erythrocytic and T-lymphocytic colony growth were carried out in a microagar culture system. At presentation, a marked diminution of CFU-M was observed, whereas CFU-E, BFU-E, CFU-C and CFU-TL were in the normal range. The CFU-M number remained at its low level during the whole observation period. The CFU-C number declined steadily during the preleukemic period, while BFU-E, CFU-E and CFU-TL remained constant until January 1985 when the patient developed AML. After progression to overt leukemia, a distinct reduction became evident in all colony-forming cells. Cytogenetic studies performed during the preleukemic phase indicated the presence of a 5q- chromosome. The authors submit evidence here that the patient was not only characterized by defective megakaryocytic colony formation but also by a deficiency of functional megakaryocyte colony-stimulating activity. No humoral or cellular inhibitors of CFU-M colony formation were found. It is concluded that in preleukemia with a 5q- chromosome the megakaryocytic cell lineage may be involved in the process that precedes overt leukemia at an earlier time than cells of granulocytic and erythrocytic lineages. In addition, it is shown here that megakaryocytopoiesis during the preleukemic period can be characterized by two different defects: first, an intrinsic megakaryocytic stem cell defect and, second, a deficiency of functional megakaryocytic colony-stimulating activity. PMID:3498097

  20. Evaluation of the effects of and earliest response rate to anti-D treatment in children with chronic idiopathic thrombocytopenic purpura: a pilot study.

    PubMed

    Yetgin, Sevgi; Aytaç, Selin; Olcay, Lale; Tunç, Bahattin; Ozbek, Namik; Aydinok, Ye?im

    2010-01-01

    In this pilot study, 30 (14 male, 16 female; median age: 8 years, range: 2-18) chronic non-splenectomized idiopathic thrombocytopenic purpura (ITP) patients with Rh+ blood group and their 49 attacks were evaluated after intravenous (i.v.) anti-D (WinRho SDF, Cangene Corporation, Winnipeg, MB, Canada) treatment at a dose of 50 microg/kg x 3 days (n = 21 cases; 35 attacks) or a single dose of 75 microg/kg (n = 9 cases; 14 attacks) to define the hemostatic dose of anti-D. Five of 30 patients (22/49 attacks) were resistant to steroid, intravenous immunoglobulin (IVIG) and vincristine treatment. Hemoglobin (Hb), white blood cells (WBC), platelets (plt) and reticulocytes (ret) were evaluated before and after treatment during the follow-up in sequences on the 1st, 7th, 14th and 21st days after anti-D treatment if the patients had no symptom. All patients, even the resistant ones, experienced an increase in plt count to provide protection from bleeding (> or = 20 x 10(9)/L in patients with symptoms, > or = 10 x 10(9)/L in patients without symptoms). The plt responses of one resistant and five non-resistant patients treated with a single 75 microg/kg dose of i.v. anti-D in 8 attacks were monitored at the 2nd, 4th, 8th, 24th and 48th hours of the treatment. A protective plt level was attained within 2 hours in 6 attacks of five non-resistant cases and in 24 hours in the remaining 2 attacks of one resistant case. This pilot study suggests that anti-D treatment in ITP patients is effective and can increase plt to a level adequate enough to protect from hemorrhage within 2 hours, when given in a 75 microg/kg dose. A few adverse events (i.e. chills, hemolysis and hemoglobinuria) resolved without intervention. PMID:20560246

  1. Efficacy, safety, and dose response of intravenous anti-D immune globulin (WinRho SDF) for the treatment of idiopathic thrombocytopenic purpura in children.

    PubMed

    Freiberg, A; Mauger, D

    1998-01-01

    We analyzed data from 20 children treated for acute or chronic idiopathic (immune) thrombocytopenic purpura (ITP) at a single institution to determine the relationship between dose of intravenous anti-D immune globulin (WinRho SDF; Nabi, Boca Raton, FL), increase in platelet count, and decrease in hemoglobin in the therapy of ITP. Higher doses of anti-D were clearly associated with a greater therapeutic response in the platelet count, with no increase in hemolysis for both acute and chronic ITP. A significant correlation was found between dose and peak increase in platelet count measured in the 14 days following administration. This effect was present for both acute ITP (17 infusions, P = .0001) and chronic ITP (30 infusions, P = .038). Although hemolysis was seen in nearly all infusions, with a median hemoglobin fall of 1.9 g/dL (range, 0 to 4.2), the decrease in hemoglobin was greater than 2.5 for only three infusions, and the largest fall in hemoglobin (4.2) was in a child with an underlying hemolytic anemia. Furthermore, for both acute and chronic ITP there was no relationship between the decrease in hemoglobin and the dose given (P = .22), nor between the increase in platelet count and fall in hemoglobin (P = .27). This analysis supports the use of higher doses of anti-D for the treatment of ITP, and demonstrates the need for a trial of high-dose anti-D (>100 microg/kg) in acute and chronic ITP. PMID:9523746

  2. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect.

    PubMed

    Bussel, J B; Graziano, J N; Kimberly, R P; Pahwa, S; Aledort, L M

    1991-05-01

    The efficacy, toxicity, and mechanism of effect of intravenous Anti-D (Winrho) were studied in 43 Rh+ patients with immune thrombocytopenia purpura (ITP) who had not undergone splenectomy and in three already splenectomized patients. The mean platelet increase for the 43 nonsplenectomized patients was 95,000/microL (median 43,000/microL). Children had greater acute platelet responses than did adults. Human immunodeficiency virus status and duration of thrombocytopenia did not affect response. Maintenance treatment was given to patients as needed: the average interval between infusions was 24 days. The three splenectomized patients had no platelet response whatsoever. Toxicity was minimal; infusions were completed in less than 5 minutes. The generally accepted mechanism of effect of Anti-D has been Fc receptor blockade by substitution of antibody-coated red blood cells for antibody-coated platelets. Evidence is presented suggesting that the effect of IV Anti-D is not limited to Fc receptor blockade, including: (1) no correlation of parameters of hemolysis with platelet increase; (2) a 48- to 72-hour delay before platelet increase; (3) a tendency of the change in monocyte Fc receptor I expression to correlate with platelet increase; and (4) increased in vitro production of antibodies to sheep red blood cells following IV Anti-D infusion. PMID:1850307

  3. [A case of chronic idiopathic purpura].

    PubMed

    Pawlik, C; Cavatorta, E; Wauters, N

    2014-01-01

    This paper focuses though on the medical management of the chronic ITP, as well as on the controversies generated by it and the therapeutic progress. Even if the idiopathic thrombocytopenic purpura is a rather frequent cause of childhood thrombocytopenia, it remains an exclusion diagnosis to be considered only in cases of persistent isolated thrombocytopenia observed in previously healthy children (other etiology excluded by the physical examination and medical history). Idiopathic thrombocytopenic purpura (ITP) is secondary to the premature platelet lysis by antibodies targeting the platelet membrane glycoproteins. The chronic evolution is defined by a prolongation of symptoms for more than 12 months. The management of chronic ITP remains controversial. Novel treatments are on the spot, such as the rituximab and the thrombopoetin receptors' agonists (the most up-to-date therapies). We present the case of a 10 years old girl admitted in our department for recurrent diffuse purpuric lesions in the context of a chronic idiopathic purpura. The clinical aspects were classical: diffuse purpuric rash, without any other symptoms. An extended check-up was performed: it confirmed the presence of anti-platelets antibodies. PMID:24683840

  4. A comparison of intravenous immunoglobulin (2 g/kg totally) and single doses of anti-D immunoglobulin at 50 ?g/kg, 75 ?g/kg in newly diagnosed children with idiopathic thrombocytopenic purpura: Ankara hospital experience.

    PubMed

    Alioglu, Bulent; Ercan, Sirma; Tapci, Ayse Esra; Zengin, Tugba; Yazarli, Esra; Dallar, Yildiz

    2013-07-01

    We conducted this prospective randomized trial of intravenous immunoglobulin (IVIG) treatment in children with newly diagnosed immune thrombocytopenic purpura (ITP) to compare the efficacy of IVIG to standard and higher doses of anti-D IVIG. Seventy-eight patients who were previously untreated and between the age of 1 and 18 years with newly diagnosed acute ITP and a platelet concentration less than 20×10/l were eligible for enrollment. In this study IVIG treatment was compared with two different doses of anti-D. Study patients were randomized to receive treatment according to one of the two single anti-D IVIG doses [50 ?g/kg (n=19) or 75 ?g/kg (n=20)] or 2 g/kg (400 mg/kg per day, 5 day) total dose of IVIG (n=39). There is a significant increase of 24th hour, 48th hour, 72nd hour, 7th day and 30th day platelet counts in IVIG (2 g/kg, total dose) group compared to anti-D IVIG 50 ?g/kg and anti-D IVIG 75 ?g/kg groups. However, there were no difference between 24th hour, 48th hour, 72nd hour, 7th day and 30th day platelet counts across anti-D IVIG 50 ?g/kg and anti-D IVIG 75 ?g/kg groups. In conclusion, this study suggests that IVIG is well tolerated and significantly more effective than standard and high-dose anti-D IVIG for the treatment of newly diagnosed ITP in children. Apart from this, we believe that IVIG might be the first-line treatment of these patients. Regarding this issue further prospective studies comparing different IVIG treatment regimens with anti-D IVIG treatment regimens are needed. PMID:23470649

  5. Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

    PubMed Central

    Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

    2012-01-01

    BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

  6. Effects of cytotoxin-associated gene A (CagA) positive Helicobacter pylori infection on anti-platelet glycoprotein antibody producing B cells in patients with primary idiopathic thrombocytopenic purpura (ITP)

    PubMed Central

    Cheng, Yuan-Shan; Kuang, Li-Ping; Zhuang, Chun-Lan; Jiang, Jia-Dian; Shi, Man

    2015-01-01

    Objective: To explore the effects of cytotoxin-associated gene A (CagA) positive Helicobacter pylori (H. pylori or HP) infection on circulating B cells producing specific platelet glycoprotein antibodies and the association between therapeutic outcomes in primary idiopathic thrombocytopenic purpura (ITP) patients. Methods: A total of 76 newly diagnosed primary ITP patients were included in the study which was conducted at the first affiliated hospital of Shantou University Medical college, in Shantou city China, between January 2013 and January 2014. These patients were tested for H. pylori infection by 13C urea breath test and for anti-CagA antibody in H. pylori positive cases by enzyme-linked immunosorbent assay (ELISA) method. Anti-GPIb and anti-GPIIb/IIIa antibody-producing B cells were measured using an enzyme-linked immunospot (ELISPOT) assay in all ITP patients and 30 controls. Anti-nuclear antibody (ANA) was also detected in ITP patients. Results: The numbers of anti-GPIIb/IIIa antibody-producing B cells in HP+CagA+ patients were higher than in HP+CagA- or HP- patients. However, anti-GPIb antibody-producing B cells were found higher in HP- patients. Analysis of treatment outcomes showed that a therapeutic response was more likely in patients presenting anti-GPIIb/IIIa B cells, but the poor response was found to be associated with anti-GPIb B cells and ANA presences. Conclusion: CagA antigen of H. pylori may induce anti-GPIIb/IIIa antibodies production by a molecular mimicry mechanism. Anti-GPIIb/IIIa and anti-GPIb antibody producing B Cells detection is useful for predicting treatment effects of primary ITP. PMID:25878627

  7. Paroxysmal drastic abdominal pain with tardive cutaneous lesions presenting in Henoch-Schönlein purpura.

    PubMed

    Chen, Xiao-Liang; Tian, Hong; Li, Jian-Zhong; Tao, Jin; Tang, Hua; Li, Yang; Wu, Bin

    2012-04-28

    Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis mediated by IgA-immune complex deposition. It is characterized by the clinical tetrad of non-thrombocytopenic palpable purpura, abdominal pain, arthritis and renal involvement. The diagnosis of HSP is difficult, especially when abdominal symptoms precede cutaneous lesions. We report a rare case of paroxysmal drastic abdominal pain with gastrointestinal bleeding presented in HSP. The diagnosis was verified by renal damage and the occurrence of purpura. PMID:22563183

  8. How Is Thrombotic Thrombocytopenic Purpura Treated?

    MedlinePLUS

    ... and surgery. Treatments are done in a hospital. Plasma Therapy Plasma is the liquid part of your blood. It ... nutrients to your body. TTP is treated with plasma therapy. This includes: Fresh frozen plasma for people ...

  9. Purpura fulminans

    Microsoft Academic Search

    Lata Kumar; B. R. Thapa; R. K. Kaushal; S. R. Bushnurmath

    1987-01-01

    Seven children with purpura fulminans are reported. All were very sick and had extensive purpuric and ecchymotic skin lesions.\\u000a Five of them had septicemia, one had meningitis and one had viral respiratory tract infection. The bacteria cultured were\\u000a Staphylococcus aureus (1), Hemophilus influenzae (1), Pseudomonas aeroginosa (1), Klebsiella pneumoniae (1) and Neisseria\\u000a meningitidis (2). Consumptive coagulopathy was present in all.

  10. Prednisolone purpura.

    PubMed

    Singhvi, G R; Chordiya, A V

    1989-08-01

    Corticosteroids, though known to act effectively against allergy and hypersensitivity, may themselves produce such reactions, ranging from urticaria to anaphylaxis. A middle-aged man with collagen vascular disease developed purpuric rash on repeated administration of steroids. This acute purpuric reaction with sequential colour changes is different than the more common senile purpura-like lesions induced by intake of steroids. It is also different than the purpuric lesions associated with collagen vascular disease per se. The present case favours an allergic aetiology. PMID:2533597

  11. Henoch-Schonlein purpura

    MedlinePLUS

    Anaphylactoid purpura; Vascular purpura; Leukocytoclastic vasculitis ... Ardoin SP, Fels E. Vasculitis syndromes. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics . 19th ed. Philadelphia, Pa: Saunders ...

  12. Safety and Efficacy Study of Romiplostim to Treat ITP in Pediatric Subjects

    ClinicalTrials.gov

    2015-07-13

    Idiopathic Thrombocytopenic Purpura; Thrombocytopenia; Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenic Purpura; Immune Thrombocytopenia

  13. Safety and Efficacy Study of Romiplostim to Treat ITP in Pediatric Subjects

    ClinicalTrials.gov

    2015-04-21

    Idiopathic Thrombocytopenic Purpura; Thrombocytopenia; Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenic Purpura; Immune Thrombocytopenia

  14. Different Specificities of Platelet-Associated and Plasma Autoantibodies to Platelet GPIIb-IIIa in Patients With Chronic Immune Thrombocytopenic Pur pur a

    Microsoft Academic Search

    K. Fujisawa; P. Tani; T. E. O'Toole; M. H. Ginsberg; R. McMillan

    1992-01-01

    Chronic immune thrombocytopenic purpura (ITP) is an auto- immune disorder due to antiplatelet autoantibodies, many of which are directed against platelet membrane glycoprotein (GP) Ilb-llla or GPlb-IX. In a recent study, we described plasma autoantibodies from 13 selected ITP patients, which required the presence of the putative GPllla cytoplasmic region for antibody binding. Since this region may not be available

  15. [A case of successfully treated cyclic amegakaryocytic thrombocytopenic purpura].

    PubMed

    Telek, B; Kiss, A; Pecze, K; Ujhelyi, P; Rák, K

    1990-05-20

    The case of a patient with cyclic, acquired, periodically amegakaryocytic thrombocytopenia is described. On the base of a seemingly typical megakaryocytic thrombocytopenia ITP was diagnosed at first. He did not respond to steroid, therefore splenectomy was performed. He relapsed and thereafter severe thrombocytopenia was observed, periodically, for 8-10 days in every five-six weeks. During the cytopenic periods recognizable megakaryocytes and precursors were totally absent from the bone marrow. After the haemorrhagic periods platelet counts elevated to normal or even higher levels and the marrow was plenty of megakaryocytes. Vincristine was unsuccessful, but cyclosporine administration for a longer time was not without success. The patient has a normal platelet count since one year. No similar case of cyclic amegakaryocytic thrombocytopenia was found in the literature. PMID:2345648

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

    PubMed Central

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

    2013-01-01

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

  17. Thrombosis warning in children suffering from henoch-schonlein purpura.

    PubMed

    Li, Luan; Zhang, Jingwen; Zhang, Yunying; Ji, Hong

    2013-09-01

    Henoch-Schonlein Purpura (HSP) is one of the most common types of vasculitis in children. The characteristic clinical manifestations include non-thrombocytopenic purpura, arthritis or arthralgia, abdominal pain, gastrointestinal hemorrhage and renal abnormalities. Thrombosis has been reported as, a rare complication of HSP. We present the case of a 14-year-old boy who was diagnosed with HSP and suspected superior mesenteric vein thrombosis. We reviewed the relevant literature and found eight similar reported cases. HSP is associated with thrombosis and HSP itself and some risk factors may result in thrombosis. We suggest that physicians should monitor patients with HSP who are at a higher risk of developing thrombosis more closely. PMID:24082216

  18. Idiopathische thrombozytopenische Purpura

    Microsoft Academic Search

    Paul Imbach; Thomas Kühne; Gerhard Gaedicke

    Die Ursache der idiopathischen thrombozytopenischen Purpura (ITP) ist noch weitgehend unbekannt. Die Pathophysiologie ist\\u000a (auto-)immunologisch. Erkenntnisse der veränderten Kaskade der Immunantwort führten zu modernen biologischen Therapieansätzen.\\u000a Prospektive kooperative Studien zeigen neue Aspekte der Demographie, des Verlaufs und der Betreuung bzw. Behandlung von Kindern\\u000a mit ITP auf.

  19. Production of target-specific recombinant human polyclonal antibodies in mammalian cells.

    PubMed

    Wiberg, Finn C; Rasmussen, Søren K; Frandsen, Torben P; Rasmussen, Lone K; Tengbjerg, Kaja; Coljee, Vincent W; Sharon, Jacqueline; Yang, Chiou-Ying; Bregenholt, Søren; Nielsen, Lars S; Haurum, John S; Tolstrup, Anne B

    2006-06-01

    We describe the expression and consistent production of a first target-specific recombinant human polyclonal antibody. An anti-Rhesus D recombinant polyclonal antibody, Sym001, comprised of 25 unique human IgG1 antibodies, was produced by the novel Sympress expression technology. This strategy is based on site-specific integration of antibody genes in CHO cells, using the FRT/Flp-In recombinase system. This allows integration of the expression construct at the same genomic site in the host cells, thereby reducing genomic position effects. Different bioreactor batches of Sym001 displayed highly consistent manufacturing yield, antibody composition, binding potency, and functional activity. The results demonstrate that diverse recombinant human polyclonal antibody compositions can be reproducibly generated under conditions directly applicable to industrial manufacturing settings and present a first recombinant polyclonal antibody which could be used for treatment of hemolytic disease of the newborn and/or idiopathic thrombocytopenic purpura. PMID:16596663

  20. Acquired amegakaryocytic thrombocytopenic purpura with humoral inhibitory factor for megakaryocyte colony formation.

    PubMed

    Katai, M; Aizawa, T; Ohara, N; Hiramatsu, K; Hashizume, K; Yamada, T; Kitano, K; Saito, H; Shinoda, T; Wakata, S

    1994-03-01

    A 67-year-old man with thrombocytopenia, and amegakaryocytic but otherwise normal bone marrow, was evaluated. Antibody against thrombocytes was negative and the half-life of thrombocytes was normal. In vitro clonal culture of the patient's bone marrow cells yielded no megakaryocyte colony with normal granulocyte-macrophage and erythroid colony formation. Megakaryocyte colony formation of the control bone marrow cells was significantly suppressed by the addition of the patient's serum to the culture, suggesting the existence of humoral inhibitory factor(s) for megakaryocyte colony formation. Therapeutic trials with plasma exchange, cyclosporine, prednisolone, and cyclosporine plus prednisolone were all unsuccessful, but serious bleeding has been absent. PMID:8061390

  1. Good response to cyclosporin in a child with acquired thrombocytopenic purpura.

    PubMed

    Jain, Shuchita; Kapoor, Seema; Singh, Ankur; Ravi, R N Mandal; Jain, Silky

    2012-09-01

    Acquired amegakaryocytic thrombocytopenia is an unusual hematological disorder characterized by thrombocytopenia along with markedly diminished megakaryocytes in the bone marrow. There is no uniform consensus on the treatment and the case reports in pediatric age group are few. The authors report a child with this condition who responded to cyclosporine alone. PMID:22170114

  2. Long term platelet responses to Helicobacter pylori eradication in Canadian patients with immune thrombocytopenic purpura

    Microsoft Academic Search

    Shannon C. Jackson; Paul Beck; Andre G. Buret; Pamela M. O’Connor; Jonathan Meddings; Graham Pineo; Man-Chiu Poon

    2008-01-01

    This prospective Canadian pilot study assesses the platelet response rate in H. pylori positive and negative patients and evaluates potential mechanisms to explain response. Patients with ITP received H. pylori eradication therapy and platelet counts at day 56 were used to assess response. Gastric permeability, stool H. pylori antigen and serum CagA anti-body were done at baseline and at day

  3. Thrombotic thrombocytopenic purpura and its look-alikes: a single institution experience.

    PubMed

    Bellone, Michael; Chiang, Jason; Ahmed, Tahmeena; Galanakis, Dennis; Senzel, Lisa

    2012-02-01

    At presentation, variant or "look-alike" conditions can resemble TTP. We reviewed charts of 26 consecutive patients treated for presumed TTP. Of 15 classic TTP patients, 11 were tested for ADAMTS13; all showed severe deficiency, and inhibitor levels correlated with probability of relapse. The variant TMA group consisted of 8 patients who had active clinical disorders which overlapped with TTP. Variant TMA patients had higher creatinine and worse prognosis than classic TTP patients. "Look-alike" disorders included ITP with intravascular hemolysis following administration of WinRho™, and human granulocytic anaplasmosis. These conditions had not been previously described as TTP look-alikes. PMID:22154043

  4. Treatment of childhood idiopathic thrombocytopenic purpura with Rhesus antibodies (anti-D)

    Microsoft Academic Search

    T. Becker; E. Kiienzlen; A. Salama; R. Mertens; V. Kiefel; H. Weiß; F. Lampert; G. Gaedicke; C. Mueller-Eckhardt

    1986-01-01

    We have recently reported that a rise of platelet numbers in ITP can be induced by blockade of the RES with antibody-coated red blood cells. We now present a collaborative study in which 15 Rhesus-positive children with ITP (nine boys and six girls aged 1–15 years) were treated with low-dose anti-D. Ten patients had chronic ITP (duration 6–47 months), five

  5. Drug-induced chronic pigmented purpura.

    PubMed

    Nishioka, K; Katayama, I; Masuzawa, M; Yokozeki, H; Nishiyama, S

    1989-06-01

    A close correlation between purpuric reaction and drugs was observed in seven cases of chronic pigmented purpura. The patients developed purpuric lesions after taking certain drugs for more than 3 years, were thiamine propyldisulfide in 2 cases, and chlordiazepoxide in 1 case. The purpuric lesions stopped recurring after removal of the drugs in the rest of the cases. It is suggested that drugs are among the etiological factors in chronic pigmented purpura. PMID:2507607

  6. Henoch-Schönlein purpura in children

    PubMed Central

    Bluman, Joel; Goldman, Ran D.

    2014-01-01

    Abstract Question A child recently presented to my office with lower limb petechiae, arthralgia, and abdominal pain characteristic of Henoch-Schönlein purpura (HSP). Will systemic corticosteroids help relieve these symptoms and prevent potential HSP complications such as intussusception and nephritis? Answer Henoch-Schönlein purpura is a common and self-limiting disease in children. Current evidence does not support universal treatment of HSP with corticosteroids. Recent trials and meta-analyses found that corticosteroids do not prevent the onset of renal disease or abdominal complications. However, corticosteroids are effective as treatment of abdominal pain, arthralgia, and purpura. Clinicians are advised to use their discretion in choosing which patients might benefit most from oral corticosteroid treatment. PMID:25551129

  7. Indian tick typhus presenting as Purpura fulminans

    PubMed Central

    Tirumala, Suhasini; Behera, Bijayini; Jawalkar, Srikanth; Mishra, Pradeep Kumar; Patalay, Pavithra Vani; Ayyagari, Sudha; Nimmala, Pavani

    2014-01-01

    Seriously ill patients presenting with purpura fulminans, sepsis and multi-organ failure often require extensive diagnostic workup for proper diagnosis and management. Host of common infections prevalent in the tropics, e.g. malaria, dengue; other septicemic infections e.g. meningococcemia, typhoid, leptospirosis, toxic shock syndrome, scarlet fever, viral exanthems like measles, infectious mononucleosis, collagen vascular diseases (Kawasaki disease, other vasculitis) diseases, and adverse drug reactions are often kept in mind, and the index of suspicion for rickettsial illness is quite low. We present a case of Indian tick typhus presenting with purpura fulminans (retiform purpura all over the body), sepsis and multiorgan failure without lymphadenopathy and eschar, successfully treated with doxycycline and discharged home. Hence, a high index clinical suspicion and prompt administration of a simple therapy has led to successful recovery of the patient. PMID:25097365

  8. Psychogenic Purpura (Gardner-Diamond Syndrome)

    PubMed Central

    Bhattacharya, Gaurav

    2015-01-01

    Psychogenic purpura, also known as Gardner-Diamond syndrome or autoerythrocyte sensitization syndrome, is a rare condition characterized by spontaneous development of painful edematous skin lesions progressing to ecchymosis over the next 24 hours. Severe stress and emotional trauma always precede the skin lesions. The condition is most commonly seen in women, but isolated cases have been reported in adolescents and in males. Psychodermatologic evaluation and dermatology and psychiatry liaison have been successful in the treatment of these patients. This report provides an overview of psychogenic purpura and presents the case of a 15-year-old girl. PMID:26137346

  9. Henoch- Schönlein Purpura Associated with Major Complications

    Microsoft Academic Search

    Mohammad Zahidul Islam

    2010-01-01

    Henoch Schönlein Purpura is a vasculitis syndrome involving small vessels and characterized by deposition of IgA1 in the renal mesangium and in the blood vessels. It can occur at any age but occurs mostly between the ages of 3 to 15 years, more commonly in boys. The onset of HSP maybe preceded by a upper respiratory tract infection. HSP is

  10. Henoch–Schonlein purpura in mesothelioma

    PubMed Central

    Joshi, Stuti; Pillai, Sooraj; Chakera, Aron; Lee, Y C Gary

    2014-01-01

    Henoch–Schonlein purpura (HSP) is primarily a childhood immunoglobulin A (IgA)-mediated illness. When adults are affected, malignancy can be associated. We present a rare case of HSP in a 75-year-old man with malignant pleural mesothelioma. He presented with episodes of dizziness and subsequently developed non-palpable purpura across his legs, arthralgia, hematuria, proteinuria, and acute renal impairment. HSP was diagnosed based on clinical and histological findings on biopsy specimens from the skin and kidney that showed a leukocytoclastic vasculitis and mesangioproliferative glomerulonephritis with IgA deposits, respectively. He was treated with high-dose oral steroids with resolution of the skin and renal manifestations of the disease. HSP is rare in adults but has been linked to cancers. This is the first report of HSP in a patient with known malignant pleural mesothelioma. PMID:25530863

  11. Post-transfusion Purpura: A Heterogeneous Syndrome

    Microsoft Academic Search

    Zella Zeigler; Scott Murphy; Frank H. Gardner

    2010-01-01

    Three new patients with post-transfusion purpura (PTP) are described. As the mani- festations in two differ significantly from those of previously reported cases, they serve to expand the definition of this syn- drome. Although all 14 previously re- pOrted cases have occurred in PlAlnega? five females, one of our patients was a PIAlnegative male. Moreover, a female whose postrecovery platelets

  12. Primary antiphospholipid syndrome presenting as complicated Henoch-Schönlein purpura.

    PubMed

    Monastiri, K; Selmi, H; Tabarki, B; Yacoub, M; Mahjoub, T; Essoussi, A S

    2002-02-01

    A child showing signs of Henoch-Schönlein purpura developed a right tibiofibular vascular thrombosis. Antiphospholipid antibody tests were positive for both lupus anticoagulant and anticardiolipin antibodies. This suggests that an antiphospholipid syndrome should be considered in cases of Henoch-Schönlein purpura and antiphospholipid antibodies should be measured to determine whether prophylactic antithrombotic measures are needed to prevent thrombotic manifestations. PMID:11827910

  13. Rare Association of Henoch-Schönlein Purpura with Recurrent Endocarditis

    PubMed Central

    Berquist, Jilaine Bolek; Bartels, Christie Michels

    2011-01-01

    We report a rare association of Henoch-Schönlein Purpura with recurrent endocarditis in a 36 year old male patient presenting with rash and renal failure. Bacterial endocarditis can be complicated by renal failure of various etiologies. Biopsy may distinguish these and guide therapy as seen in this case. Here, timely diagnosis of Henoch-Schönlein Purpura in the setting of recurrent methacillin sensitive staphylococcus endocarditis, led to steroid therapy and renal recovery. This is a rare reported case of Henoch-Schönlein Purpura during an episode of recurrent adult endocarditis that also highlights the complex interplay between genetic susceptibility and immune responses. PMID:21473512

  14. Infarctive purpura hemorrhagica in five horses.

    PubMed

    Kaese, Heather J; Valberg, Stephanie J; Hayden, David W; Wilson, Julia H; Charlton, Patricia; Ames, Trevor R; Al-Ghamdi, Ghanem M

    2005-06-01

    Five horses were examined because of signs of muscle stiffness, colic, or both. All 5 had been exposed to Streptococcus equi within 3 weeks prior to examination or had high serum titers of antibodies against the M protein of S equi. Horses had signs of unrelenting colic-like pain and focal areas of muscle swelling. Four horses were euthanatized. The fifth responded to treatment with penicillin and dexamethasone; after 3 weeks of treatment with dexamethasone, prednisolone was administered for an additional 10 weeks. Common hematologic and serum biochemical abnormalities included neutrophilia with a left shift and toxic changes, hyperproteinemia, hypoalbuminemia, and high serum creatine kinase and aspartate transferase activities. Necropsy revealed extensive infarction of the skeletal musculature, skin, gastrointestinal tract, pancreas, and lungs. Histologic lesions included leukocytoclastic vasculitis in numerous tissues and acute coagulative necrosis resembling infarction. These horses appeared to have a severe form of purpura hemorrhagica resembling Henoch-Schönlein purpura in humans and characterized by infarction of skeletal muscles. Early recognition of focal muscle swelling, abdominal discomfort, neutrophilia, hypoalbuminemia, and high serum creatine kinase activity combined with antimicrobial and corticosteroid treatment may enhance the likelihood of a successful outcome. PMID:15934258

  15. [Schoenlein-Henoch purpura with intestinal involvement].

    PubMed

    Blöchinger, M; Schmitt, W; Beer, M; Seib, H J

    1997-11-01

    A 51-year-old male patient admitted to the hospital because of colic-like abdominal pain, paralytic ileus, anal bleeding and microhaematuria with proteinuria, developed an intestinal ischemia with a serum lactate level of 6.3 mmol/l. An occlusion of the large vessels was excluded angiographically. Perfusion disorders were detected both endoscopically and histologically in the upper gastrointestinal tract and in the terminal ileum. When after two days a palpable purpura appeared on the anterior of both feet, a vasculitis type Schoenlein-Henoch was suspected and treated with high doses of steroids, resulting in decreasing symptoms. From the point of admittance, a nephritic urinary sediment had been apparent, and the renal affliction developed into a nephrotic syndrome without notable reduction in the glomerular filtration rate. On the 13th day of treatment the patient-being on a reduced dose of steroids-suffered from a severe relapse; however, this responded favorably to an increase of the dosage. The kidneys required approximately one year for complete recovery. Based on this case, the Schoenlein-Henoch purpura syndrome and its differential diagnosis are presented, particularly with respect to gastrointestinal symptoms and in view of the pertinent literature. PMID:9490551

  16. Colony-forming unit-megakaryocyte (CFR-meg) numbers and serum thrombopoietin concentrations in thrombocytopenic disorders: an inverse correlation in myelodysplastic syndromes.

    PubMed

    Wang, W; Matsuo, T; Yoshida, S; Mori, H; Miyazaki, Y; Kuriyama, K; Tomonaga, M

    2000-10-01

    We studied both serum-free colony-forming unit-megakaryocyte (CFU-meg) numbers and serum thrombopoietin (TPO) levels in 14 patients with aplastic anemia (AA), 37 patients with myelodysplastic syndromes (MDS) and 23 patients with idiopathic thrombocytopenic purpura (ITP) to assess thrombopoiesis in these thrombocytopenic disorders. The mean CFU-meg numbers were lower in AA and MDS patients (10.7 +/- 11.4 and 42.3 +/- 58.5/10(5) BMLD cells) than in healthy controls (103.1 +/- 57.3/10(5) BMLD cells) (P < 0.0001 and P= 0.0053, respectively), although they were distributed variably in MDS. ITP patients showed higher CFU-meg numbers (223.2 +/- 143.5/10(5) BMLD cells) (P= 0.017). The mean TPO concentrations were higher in both AA (986.8 +/- 500.8 pg/ml) and MDS patients (838.2 +/- 639.1 pg/ml) than in healthy controls (80.7 +/- 38.8 pg/ml) (P < 0.0001), although they were distributed from high to low in MDS. ITP patients showed a slight elevation of TPO (123.1 +/- 55.3 pg/ml) P = 0.0106). The TPO levels was inversely correlated to both platelet counts and CFU-meg numbers (correlative coefficient (CC): -0.719 and -0.682, P < 0.0001) in AA, but not in ITP. In MDS, the inverse correlation to TPO was stronger in CFU-meg (CC: -0.678, P < 0.0001) than in platelet counts (CC: -0.538, P = 0.0014), suggesting that CFU-meg plays an important role in regulating TPO production in this heterogenous disorder. CFU-meg and TPO may provide useful information for understanding thrombopoiesis of MDS, especially for application of TPO. PMID:11021750

  17. [Henoch-Schönlein purpura resulting in an obstructive bladder mass].

    PubMed

    Comploj, E; Cassar, W; Trenti, E; Palermo, S; Reinstadler, P; Ladurner, C; Dechet, C; Pycha, A

    2013-11-01

    Henoch-Schönlein purpura (HSP) is the most common form of an immunological systemic vasculitis of childhood. The classic clinical symptoms include purpuric rash, abdominal pain, arthralgias, and haematuria, but the spectrum of HSP may vary to very rare forms. This article reports on an 8-year-old girl with a Henoch-Schönlein purpura (HSP) which resulted in an obstructive bladder mass and subsequent urinary retention. This is the first case reported in the literature, describing such a course. PMID:23824929

  18. Neurologic manifestations of Henoch-Schönlein purpura.

    PubMed

    Bérubé, Maxime D; Blais, Normand; Lanthier, Sylvain

    2014-01-01

    Henoch-Shönlein purpura (HSP) is a systemic small vessel vasculitis. Most patients present during childhood. The characteristic association of purpura, arthralgia, abdominal pain, and nephritis reflects the predominant distribution of vasculitis. Headaches and mild behavioral changes suggest CNS involvement in one-third of HSP patients. Salient central nervous system (CNS) manifestations are rarer and mostly reported in adults and patients with a severe disease course. Diagnosis of CNS vasculitis is rarely confirmed by histopathology and generally relies on "suggestive" imaging showing brain hemorrhages, infarcts and edema, predominantly located in the parieto-occipital regions. Vessel wall friability and thrombogenicity of active vasculitis, antiphospholipid antibody synthesis, and other hemostatic disturbances may contribute to hemorrhagic and thrombotic complications of HSP. Posterior reversible encephalopathy syndrome and hypertensive encephalopathy occur in HSP and can be difficult to differentiate from CNS vasculitis. Some 53% of patients with neurologic complications experience seizures. Cerebral venous thrombosis, subdural hematoma, subarachnoidal hemorrhage, neuro-ophthalmologic complications, myelopathy, and diverse neuromuscular manifestations are also reported. In contrast with other systemic small vessel vasculitides, peripheral nervous system involvement is infrequent in HSP. Systemic involvement of HSP and homeostatic disorders such as hypertension, uremia, and electrolyte disturbances, as well as superimposed infections can affect the nervous system secondarily. Identification of nervous system complications of HSP is often challenging due to prominent systemic manifestations. HSP is usually a self-limiting disease that requires only supportive care. Patients with CNS vasculitis are commonly treated with corticosteroids. One-fifth of patients with CNS involvement remain with sequelae. PMID:24365374

  19. Staphylococcal Purpura Fulminans: Report of a Case.

    PubMed

    Honarpisheh, Hedieh; Camp, Robert; Lazova, Rossitza

    2015-08-01

    Purpura fulminans (PF) is associated with several infections and most commonly with meningococcemia. However, there are only a few reports of this entity in association with toxic shock syndrome toxin-1-producing Staphylococcus aureus. We report a 53-year-old man who presented with fever, progressive hemodynamic instability, multiorgan failure, and thrombocytopenia following lobectomy for a solitary lung metastasis from rectal adenocarcinoma. He developed progressive generalized eruption of nonblanching red, purple, and black macules, papules, and plaques on the trunk and extremities consistent with PF. He died on postadmission day 3. Autopsy examination revealed purulent pleural exudate, which grew toxic shock syndrome toxin-1-producing S. aureus. Premortem and autopsy skin biopsies demonstrated epidermal necrosis, subepidermal bullae, and fibrin thrombi within small cutaneous vessels with minimal perivascular lymphocytic inflammation and without accompanying vasculitis. With this case report, we would like to draw attention to the fact that staphylococcal toxic shock syndrome-associated PF may be highly underrecognized and much more common than reflected in the literature. PMID:25099358

  20. Danazol: an effective option in acquired amegakaryocytic thrombocytopaenic purpura.

    PubMed

    Mulroy, E; Gleeson, S; Chiruka, S

    2015-01-01

    Acquired amegakaryocytic thrombocytopaenic purpura (AATP) is a rare haematological condition characterised by isolated thrombocytopaenia with normal other cell lines. It is often initially misdiagnosed as immune thrombocytopaenic purpura but has characteristic bone marrow findings of reduced megakaryocyte numbers. The optimal treatment of AATP is not clearly defined but revolves around immunosuppressive therapies. We report a case of successful treatment of AATP with danazol, an antioestrogenic medication. We also review the aetiologies and pathogenesis of the disorder and suggest that danazol should be considered as an effective alternative to potent immunosuppression in AATP. PMID:25945269

  1. Danazol: An Effective Option in Acquired Amegakaryocytic Thrombocytopaenic Purpura

    PubMed Central

    Mulroy, E.; Gleeson, S.; Chiruka, S.

    2015-01-01

    Acquired amegakaryocytic thrombocytopaenic purpura (AATP) is a rare haematological condition characterised by isolated thrombocytopaenia with normal other cell lines. It is often initially misdiagnosed as immune thrombocytopaenic purpura but has characteristic bone marrow findings of reduced megakaryocyte numbers. The optimal treatment of AATP is not clearly defined but revolves around immunosuppressive therapies. We report a case of successful treatment of AATP with danazol, an antioestrogenic medication. We also review the aetiologies and pathogenesis of the disorder and suggest that danazol should be considered as an effective alternative to potent immunosuppression in AATP. PMID:25945269

  2. “Benign” hypergammaglobulinemic purpura is not benign in pregnancy

    Microsoft Academic Search

    Elaine C. Jolly; Beverley J. Hunt; Spencer Ellis; Malcolm Griffiths; Ken Farrington

    2009-01-01

    A woman presented at 25 weeks gestation in her first pregnancy with severe preeclampsia and an intrauterine death. It later\\u000a emerged that she had Waldenstrom’s benign hypergammaglobulinemic purpura. We discuss the implications of this diagnosis in\\u000a pregnancy and explore possible management options during subsequent pregnancies.

  3. Cutaneous vasculitis in ulcerative colitis mimicking Henoch-Schönlein purpura.

    PubMed

    de Oliveira, Guilherme Trudes; Martins, Sofia Simão; Deboni, Mariana; Picciarelli, Patrícia; Campos, Lúcia Maria Arruda; Jesus, Adriana Almeida; Koda, Yu Kar Ling; Silva, Clovis Artur

    2013-03-01

    To the best of our knowledge, no cases of ulcerative colitis (UC) mimicking Henoch-Schönlein purpura (HSP) have been reported so far. During a 28-year period 5635 patients were followed up at our Pediatric Rheumatology Unit and 357 had HSP according to the European League Against Rheumatism, the Paediatric Rheumatology International Trials Organisation and the Paediatric Rheumatology European Society validated classification criteria. At the same period, 148 patients with IBD according to the European Society for Paediatric Gastroenterology, Hepatology and Nutrition criteria were followed up at the Pediatric Gastroenterology Unit in our University Hospital. Only two of them had vasculitis, as an extra intestinal manifestation of UC mimicking HSP, and fulfilled both disease criteria. A 2-year old girl had bloody diarrhoea, severe abdominal pain, arthritis in ankles, petechiae and palpable purpura not related to thrombocytopenia in lower limbs. A 5-year old boy had bloody diarrhoea, palpable purpura in buttocks, lower limbs, penis and scrotum associated with arthritis in knees, orchitis in right testicle and periarticular swelling in hands and feet. Their ileocolonoscopy showed diffuse mucosal erythema, oedema, friability and multiple irregular ulcers, and histopathological examination of colonic specimen revealed diffuse chronic mucosal inflammation, crypt distortion and crypt abscesses suggesting ulcerative colitis. There were no signs of intestinal vasculitis in both cases. In conclusion, this is the first study in a paediatric population that evidenced palpable purpura associated with UC mimicking HSP. PMID:22626504

  4. Acquired Amegakaryocytic Thrombocytopenia Purpura in a Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Hanley, Patrick W; Baze, Wallace B; McArthur, Mark J; Bernacky, Bruce J; Wilkerson, Greg K; Barnhart, Kirstin F

    2012-01-01

    A 10-y-old multiparous rhesus macaque presented for an annual routine physical examination. Clinically, the animal had pale mucous membranes, petechial and ecchymotic hemorrhages in multiple sites, and a laceration at the tail base. Severe pancytopenia was noted on hematologic evaluation. The monkey was seronegative for SIV, simian T-lymphotropic virus, simian retrovirus type D, and Macacine herpesvirus 1. Bone marrow evaluation revealed a paucity of megakaryocytic precursors in a hypercellular marrow with marked erythroid hyperplasia. In light of these findings, the diagnosis was acquired amegakaryocytic thrombocytopenia purpura. Due to the poor prognosis of the syndrome and clinical deterioration of the monkey, euthanasia was elected. A definitive cause of the thrombocytopenia was not identified; however, the syndrome may have developed secondary to a recent spontaneous abortion. To our knowledge, this case represents the first reported observation of acquired amegakaryocytic thrombocytopenia purpura in a rhesus monkey. PMID:22776057

  5. Acquired amegakaryocytic thrombocytopenia purpura in a Rhesus macaque (Macaca mulatta).

    PubMed

    Hanley, Patrick W; Baze, Wallace B; McArthur, Mark J; Bernacky, Bruce J; Wilkerson, Greg K; Barnhart, Kirstin F

    2012-06-01

    A 10-y-old multiparous rhesus macaque presented for an annual routine physical examination. Clinically, the animal had pale mucous membranes, petechial and ecchymotic hemorrhages in multiple sites, and a laceration at the tail base. Severe pancytopenia was noted on hematologic evaluation. The monkey was seronegative for SIV, simian T-lymphotropic virus, simian retrovirus type D, and Macacine herpesvirus 1. Bone marrow evaluation revealed a paucity of megakaryocytic precursors in a hypercellular marrow with marked erythroid hyperplasia. In light of these findings, the diagnosis was acquired amegakaryocytic thrombocytopenia purpura. Due to the poor prognosis of the syndrome and clinical deterioration of the monkey, euthanasia was elected. A definitive cause of the thrombocytopenia was not identified; however, the syndrome may have developed secondary to a recent spontaneous abortion. To our knowledge, this case represents the first reported observation of acquired amegakaryocytic thrombocytopenia purpura in a rhesus monkey. PMID:22776057

  6. Vasculitic purpura in vinyl chloride disease: a case report

    SciTech Connect

    Magnavita, N.; Bergamaschi, A.; Garcovich, A.; Giuliano, G.

    1986-05-01

    Vinyl chloride (VC), a volatile substance mostly used for polyvinyl chloride (PVC) synthesis, is a systemic toxicant particularly noxious to endothelium. Angiosarcoma of the liver, Raynaud's phenomenon, scleroderma-like lesions, acroosteolysis and neuritis are known to be typical vinyl chloride-associated manifestations (VC disease). A so far unknown feature of the disease is purpura. This was first observed by the authors in a worker of a PVC-producing plant. The skin eruption was characterized by small purpuric maculae with tiny, palpable spots and papulae, mostly concentrated on the lower part of the legs, changing into bullae, pustules and crusts and tending to spontaneous regression after withdrawal from VC exposure. A skin biopsy revealed marked inflammatory reaction with a mostly lymphocytic and histiocytic infiltration around and in the walls of dermal arterioles. The finding of increased circulating immune complexes and anti-smooth muscle autoantibodies strengthens the hypothesis that immunologic changes play a role in the appearance of ''vinylic purpura.''

  7. Early treatment with oral immunosuppressants in severe proteinuric purpura nephritis

    Microsoft Academic Search

    Hiroshi Tanaka; Koichi Suzuki; Tohru Nakahata; Etsuro Ito; Shinobu Waga

    2003-01-01

    Nine Japanese children with severe proteinuric Henoch-Schönlein purpura nephritis (HSPN) received prompt initiation of oral prednisolone (1.5 mg\\/kg\\/day) combined with an 8-week course of cyclophosphamide (2 mg\\/kg\\/day) therapy. All underwent renal biopsy before and after treatment. At presentation, urine protein excretion and histologic indices of the mean activity index, the mean chronicity index and the tubulointerstitial (TI) scores in the

  8. Primary antiphospholipid syndrome presenting as complicated Henoch–Scho?nlein purpura

    Microsoft Academic Search

    K Monastiri; H Selmi; B Tabarki; M Yacoub; T Mahjoub; A S Essoussi

    2002-01-01

    A child showing signs of Henoch–Scho?nlein purpura developed a right tibiofibular vascular thrombosis. Antiphospholipid antibody tests were positive for both lupus anticoagulant and anticardiolipin antibodies. This suggests that an antiphospholipid syndrome should be considered in cases of Henoch–Scho?nlein purpura and antiphospholipid antibodies should be measured to determine whether prophylactic antithrombotic measures are needed to prevent thrombotic manifestations.

  9. Henoch-Schönlein purpura with intracerebral haemorrhage in an adult patient: a case report

    Microsoft Academic Search

    Lazarus Karamadoukis; Linmarie Ludeman; Anthony J Williams

    2008-01-01

    INTRODUCTION: Henoch-Schönlein purpura is a small vessel vasculitis that affects mainly the skin, joints, gastrointestinal tract and kidneys. The central nervous system is also occasionally affected, although the majority of patients experience only mild symptoms such as headaches and behavioural changes. Intracerebral haemorrhage is a rare complication of Henoch-Schönlein purpura that so far has mainly been described in children and

  10. [Purpura fulminans, venous thrombosis and constitutional thrombophilia in an infant].

    PubMed

    Fadil, F; Elfatoiki, F; Mortaji, K; Lasry, F; Itri, M; Khadir, K; Benchikhi, H; Sarbati, N; Nadifi, S

    2013-05-01

    The association of idiopathic purpura fulminans (PF) and venous thrombosis (VT) seldom reveals constitutional thrombophilia in an infant. We report a case of PF in an 18-month-old infant. Laboratory tests showed disseminated intravascular coagulation (DIVC) with normal rates of C and S proteins and antithrombin. The echo-Doppler examination conveyed venous thrombosis of the lower limbs, while the genetic study showed heterozygous mutation of Factor II (G 20210A). Precocious and multidisciplinary management included frozen fresh plasma supplementation and necrosectomy with skin grafts. The diagnosis and therapeutic problems posed by PF combined with deep venous thrombosis are discussed. PMID:23566584

  11. Purpura fulminans in a patient with mixed connective tissue disease

    PubMed Central

    Murad, Aizuri A; Jeffers, Michael; Tobin, Anne-Marie; Connolly, Maureen

    2013-01-01

    A 43-year-old lady was admitted to the intensive care unit with sepsis. She had a history of mixed connective tissue disease, Raynaud's syndrome and hypothyroidism. 2?days later, she developed a purpuric rash on her face and extremities with a livedoid background. Few days later, her distal fingers and toes became gangrenous which then had to be amputated. Laboratory investigations showed that she was coagulopathic and had multiple organ dysfunctions. Antiphospholipid antibodies were negative; however, protein C and antithrombin III levels were low. A skin biopsy showed fibrinoid necrosis in the vessel wall with microthrombi and red-cell extravasation. A diagnosis of purpura fulminans was made. PMID:23370948

  12. Purpura fulminans in a patient with mixed connective tissue disease.

    PubMed

    Murad, Aizuri A; Jeffers, Michael; Tobin, Anne-Marie; Connolly, Maureen

    2013-01-01

    A 43-year-old lady was admitted to the intensive care unit with sepsis. She had a history of mixed connective tissue disease, Raynaud's syndrome and hypothyroidism. 2 days later, she developed a purpuric rash on her face and extremities with a livedoid background. Few days later, her distal fingers and toes became gangrenous which then had to be amputated. Laboratory investigations showed that she was coagulopathic and had multiple organ dysfunctions. Antiphospholipid antibodies were negative; however, protein C and antithrombin III levels were low. A skin biopsy showed fibrinoid necrosis in the vessel wall with microthrombi and red-cell extravasation. A diagnosis of purpura fulminans was made. PMID:23370948

  13. /sup 111/In-oxine platelet survivals in thrombocytopenic infants

    SciTech Connect

    Castle, V.; Coates, G.; Kelton, J.G.; Andrew, M.

    1987-09-01

    Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous /sup 111/In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the /sup 111/In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

  14. Successful treatment of an elderly frail patient with acquired idiopathic thrombotic thrombocytopenic purpura under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers.

    PubMed

    Sano, Keigo; Yagi, Hideo; Hanamoto, Hitoshi; Fujita, Mariko; Iizuka, Takashi; Yamazaki, Keiko; Tsubaki, Kazuo

    2014-04-01

    A 68-year-old woman was admitted to the regional hospital because of hemolytic anemia, thrombocytopenia, and neurological abnormalities including unconsciousness. One week before admission, she suffered from diarrhea and subsequently passed out and hit her face on the ground. She was suspected of having TTP and was transferred to our hospital. We performed the assays of ADAMTS13 activity and anti-ADAMTS13 antibody titers, and confirmed the diagnosis of acquired idiopathic TTP with total deficiency of ADAMTS13 activity with its inhibitor. She was initially treated with plasma exchange combined with corticosteroids, however, we were forced to substitute plasma exchange with fresh frozen plasma infusion due to procedure-associated complications. The infusion of fresh frozen plasma was known as less effective and more likely to boost inhibitor titers compared to plasma exchange. In this circumstance, we could successfully switch the plasma therapy under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers which precisely revealed the disease status of TTP in our patient, and eventually she achieved complete remission with normal level of ADAMTS13 activity and no inhibitor. Our experience suggested that the measurement of ADAMTS13 activity and inhibitor titer might be valuable not only for making the diagnosis but also for guiding treatment decisions by precise evaluating of disease status in patients with the acquired form of TTP. PMID:24517874

  15. Acute renal failure in a child with thrombocytopenic purpura caused by acute Epstein-Barr virus infection after treatment with anti-D immunoglobulin.

    PubMed

    Kossiva, Lydia; Kyriakou, Dimitrios; Mitsioni, Andromachi; Garoufi, Anastasia

    2013-06-01

    Immune thrombocytopenia (ITP) in children is usually a benign, self-limiting disorder. An acute Epstein-Barr virus (EBV) infection usually causes atypical lymphocytosis and mild decrease in platelets. Severe thrombocytopenia is an extremely rare complication. Anti-D immunoglobulin has been used for treatment of ITP in Rh(D)-positive nonsplenectomized patients. Severe hemolysis and acute renal failure are extremely rare complications that may be aggravated by the presence of an acute EBV infection. It is believed that anti-D immunoglobulin triggers an unusual virus-induced immune response causing hemolysis. We present a 4-year-old girl with ITP caused by an acute EBV infection that developed acute kidney injury following treatment with anti-D immunoglobulin. The patient recovered completely from thrombocytopenia and renal dysfunction. Intravascular hemolysis and acute kidney injury are consistent with anti-D immunoglobulin mechanism of action. Pediatric patients treated with anti-D immunoglobulin for ITP should be closely monitored for signs and symptoms of hemolysis that may be aggravated by the presence of EBV infection leading to impaired renal function. PMID:23736070

  16. Do the acute platelet responses of patients with immune thrombocytopenic purpura (ITP) to IV anti-D and to IV gammaglobulin predict response to subsequent splenectomy?

    PubMed

    Bussel, J B; Kaufmann, C P; Ware, R E; Woloski, B M

    2001-05-01

    The acute platelet response to Intravenous Gammaglobulin (IVIG) has been reported to predict response to subsequent splenectomy of patients with ITP. The current study was undertaken to determine if the platelet response to IV anti-D (Winrho-SDF) predicts response to subsequent splenectomy. The 61 HIV-uninfected children and adults in this study had taken part in the pre-licensing studies of IV anti-D and were all those who not only had evaluable platelet responses to IV anti-D but also had undergone splenectomy and had information available describing its 1-year outcome. Results of treatment with IVIG were available in 38 of these 61 patients. Neither response to the initial infusion of IV anti-D, nor response to the initial or last IVIG, predicted the response in either children or adults to subsequent splenectomy. However, response to the last anti-D infusion in adults was strongly correlated (P = 0.003) to response to subsequent splenectomy as was hemolysis >/=2.0 gm/dl after IV anti-D (P = 0.03). There was no overall relationship between response to IV anti-D or IVIG, and response to subsequent splenectomy. However, a good platelet response in adults to the last IV anti-D and a hemoglobin decrease >/=2.0 gm/dl both appeared to predict response to subsequent splenectomy. PMID:11279654

  17. Connective Tissue Disease Following Hepatitis B Vaccination; Topiramate-Associated Fatal Heat Stroke; Ramelteon-Induced Autoimmune Hepatitis; Acute Oxaliplatin-Induced Thrombotic Thrombocytopenic Purpura

    PubMed Central

    2014-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24715739

  18. Henoch-schönlein purpura associated with gangrenous appendicitis: a case report.

    PubMed

    Semeena, Nk; Adlekha, Shashikant

    2014-03-01

    Henoch-Schönlein Purpura (HSP) is a leucocytoclastic vasculitis of unclear aetiology characterised by symmetrical, non-traumatic, nonthrombocytopenic purpura mostly involving the lower limbs and buttocks, as well as arthritis, gastrointestinal manifestations, and occasional nephritis. A 35 years old male presented with purpuric rash on the lower extremities, abdominal pain, fever, arthralgia, and melaena. A diagnosis of HSP with appendicitis was made, which is an exceedingly rare phenomenon. PMID:24876811

  19. Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis

    PubMed Central

    Song, Yang; Shi, Yan-Hong; He, Chong; Liu, Chang-Qin; Wang, Jun-Shan; Zhao, Yu-Jie; Guo, Yan-Min; Wu, Rui-Jin; Feng, Xiao-Yue; Liu, Zhan-Ju

    2015-01-01

    Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn’s disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX. PMID:26019477

  20. Concurrent poststreptococcal acute glomerulonephritis and Schönlein-Henoch purpura.

    PubMed

    Onisawa, S; Morishima, N; Ichimura, T

    1989-08-01

    A 5-year-old Japanese boy developed concurrent poststreptococcal acute glomerulonephritis (PSAGN) and Schönlein-Henoch purpura (SHP). An elevated titer of ASK on admission confirmed the preceding streptococcal infection. Arthritis of the left knee and petechiae on admission were regarded as features of SHP. The presence of SHP was further confirmed by the pathological finding of leukocytoclastic vasculitis in the skin. PSAGN was strongly suspected due to the findings of microscopic hematuria and hypocomplementemia in the acute phase. The concurrence of SHP and PSAGN suggests similar underlying pathophysiological processes as poststreptococcal sequelae. At the height of the illness, peripheral blood lymphocyte subset analysis showed a marked increase in the suppressor inducer T subset and a reciprocal decrease in the helper T subset. This alteration in T lymphocyte subsets was regarded as indicative of the immunological derangement in this patient. PMID:2514574

  1. Acute appendicitis in two children with Henoch-Schönlein purpura.

    PubMed

    Bilici, Salim; Akgun, Cihangir; Melek, Mehmet; Peker, Erdal; Akbayram, Sinan; Bulut, Gulay; Dogan, Murat

    2012-01-01

    In Henoch-Schönlein purpura (HSP), involvement of the ileum and ascending colon with vasculitis can mimic appendicitis and cause unnecessary appendicectomy. A 13-year-old boy presented with signs of HSP and abdominal pain. He was treated with prednisolone (2 mg/kg/day) for 10 days, but there was no improvement. At laparotomy he had acute suppurative appendicitis. A 12-year-old girl presented with HSP associated with abdominal pain and bloody diarrhoea and at laparotomy was also found to have suppurative appendicitis. Both patients had vasculitic areas in the ileum. In HSP, although suppurative appendicitis is rare, it should always be considered and appropriate investigations, including ultrasonography, undertaken. PMID:23164301

  2. Atypical Henoch-Schonlein purpura? Consider polyarteritis nodosa!

    PubMed

    Braungart, Sarah; Campbell, Alison; Besarovic, Sanja

    2014-01-01

    We describe the case of a previously healthy 12-year-old boy admitted to a tertiary paediatric centre with the clinical diagnosis of Henoch-Schonlein purpura (HSP). Symptoms on admission included a generalised rash, colicky abdominal pain, hypertension, proteinuria and fresh rectal bleeding. Abdominal pain and distension worsened and serial ultrasounds suggested bowel ischaemia. He underwent repeat laparotomy and bowel resection, with slow improvement after the second laparotomy. The severity of systemic involvement (gastrointestinal, cardiac, renal and skin) made the initial diagnosis of HSP questionable. Immunohistochemistry of skin biopsies was negative for HSP. Histopathology of the bowel specimen revealed features of necrotising small and medium vessel vasculitis in keeping with polyarteritis nodosa. PMID:24717855

  3. [Cutaneous manifestations of internal diseases: purpura, livedo, pyoderma gangrenosum].

    PubMed

    Trüeb, R M

    2003-09-01

    Dermatology and internal medicine have in common that many systemic diseases manifest with skin symptoms that are easily accessible for both diagnostic and investigative procedures. Even if modern practice of medicine tends towards organ specific particularity of specialists, dermatology traditionally strives for interdisciplinary communication. Cutaneous manifestations of internal diseases present in various forms. In a syndrome, a number of symptoms present in an identical pattern, and pattern recognition is diagnostic. Vice versa, a distinct skin sign can be a clue to various internal disorders, that have to be considered in the differential diagnosis. Purpura and livedo due to either inflammatory (immune complex mediated or associated with ANCA) or vasoocclusive microthrombotic vascular disease are presented as examples. Finally, subtile variations in key symptoms of the skin, such as of pyoderma gangrenosum, may give a clue to a specific underlying disease, such as rheumatoid arthritis, inflammatory bowel disease, monoclonal gammopathy, or hematologic disease, as exemplified by the variants of pyoderma gangrenosum. PMID:14526631

  4. Purpura thrombopénique amégacaryocytaire acquis: penser au lupus érythémateux systémique

    PubMed Central

    Ernestho-ghoud, Indretsy Mahavivola; Rahamefy, Odilon; Ranaivo, Irina Mamisoa; Andrianarison, Malalaniaina; Ramarozatovo, Lala Soavina; Rabenja, Fahafahantsoa Rapelanoro

    2015-01-01

    L'amegacaryocytose acquise est exceptionnellement décrite au cours d'un Lupus Erythémateux Systémique (LES) à Madagascar. Nous rapportons la première observation d'un Purpura Thrombopénique Amegacaryocytaire Acquis (PTAA) simulant un Purpura Thrombopénique Idiopathique (PTI) révélateur d'un LES. Il s'agissait d'une femme de 24 ans, sans antécédents particuliers. Elle présentait un syndrome hémorragique avec une thrombopénie à 10 000/mm3. Le diagnostic de PTI était retenu avant l'hospitalisation. Elle avait reçu une corticothérapie mais ceci n’était pas suivi d'amélioration. A l'unité de Dermatologie, elle se plaignait d'une baisse de l'acuité visuelle. Elle était en bon état général. On retrouvait une tachycardie à 110 bpm, un érythème malaire en verspertilio typique et une pâleur cutanéo-muqueuse. Une hémorragie oculaire bilatérale était objectivée à l'examen ophtalmologique. Les examens paracliniques montraient une thrombopénie à 31000/mm3, une anémie microcytaire à 48g/dL. Les examens immunologiques étaient non réalisés. Un LES avec atteinte cutanée et hématologique était retenu. Un bolus de corticothérapie était administrée associée à une transfusion sanguine. L’évolution était marquée par l'apparition d'un signe d'engagement cérébral faisant suspecter un neurolupus. Le scanner cérébral révélait une hémorragie cérébrale avec une hydrocéphalie aigue traitée par un inhibiteur de l'anhydrase carbonique mais le neurolupus n’était pas écarté. L'anémie disparaissait par contre la thrombopénie s'aggravait à 16000/mm3. Le médullogramme montrait l'absence des mégacaryocytes. L’évolution était favorable à huit mois de suivi après un relais per os de la corticothérapie par la dose de 1 mg/kg/j à dose dégressive à huit mois de suivi. Les atteintes neurologiques, ophtalmologiques et hématologiques étaient compatible avec le diagnostic d'un LES. La persistance d'une thrombopénie doit faire suspecter une amegacaryocytose. Le myélogramme était indispensable pour poser le diagnostic PMID:26090044

  5. Soluble thrombomodulin and antibodies to bovine glomerular endothelial cells in patients with Henoch-Schönlein purpura

    PubMed Central

    Fujieda, M.; Oishi, N.; Naruse, K.; Hashizume, M.; Nishiya, K.; Kurashige, T.; Ito, K.

    1998-01-01

    AIM—To evaluate the clinical significance of soluble thrombomodulin and antiendothelial cell antibodies (AECA) in children with Henoch-Schönlein purpura.?METHODS—Binding of serum AECA to bovine glomerular endothelial cells was evaluated by enzyme linked immunosorbent assay, cytotoxicity against glomerular endothelial cells by spectrophotometric assay, and soluble thrombomodulin concentrations by sandwich enzyme immunoassay.?RESULTS—IgA AECA were detected in seven of 15 patients with Henoch-Schönlein purpura and nephritis, but were not detected in patients without nephritis or in controls. Patients with Henoch-Schönlein nephritis had raised titres of IgA AECA and serum thrombomodulin; severe proteinuria and renal histological changes were associated with raised titres of IgA AECA and raised serum thrombomodulin. No subjects had complement dependent cytotoxicity against glomerular endothelial cells.?CONCLUSIONS—High titres of IgA AECA and raised serum thrombomodulin may be clinically useful markers of renal involvement in patients with Henoch-Schönlein purpura.?? PMID:9613354

  6. Establishing hospital admission criteria of pediatric Henoch-Schonlein purpura.

    PubMed

    Masarweh, Kamal; Horovitz, Yoseph; Avital, Avi; Spiegel, Ronen

    2014-11-01

    The current study aimed to define evidence-based admission criteria of pediatric Henoch-Schonlein purpura (HSP). In addition, we aimed to better characterize epidemiological and clinical features of pediatric HSP in Israel. We performed a retrospective cohort study of all children with HSP admitted during a 15 years period to a single pediatric department. We strictly collected the clinical data of all HSP cases. Each case was categorized as either "necessary admission" or "unnecessary admission." We compared the two groups, using initially Chi square (?(2)) and student "t" tests, and thereafter, we employed logistic stepwise regression analysis. One hundred and sixty-three children with HSP were included. A set of six clinical criteria of which the presence of minimum one predicts the need for hospitalization were identified including: orchitis, moderate or severe abdominal pain, arthritis involving more than two joints, proteinuria, clear evidence of gastrointestinal bleeding, and inability to ambulate. In conclusion, we suggest a predictive model for the admission of pediatric patients with acute HSP. The implementation of this model can significantly reduce unnecessary admissions. PMID:24563020

  7. Pneumatosis intestinalis associated with Henoch-Schönlein purpura.

    PubMed

    Fatima, Ayesha; Gibson, Donald Paul

    2014-09-01

    Henoch-Schönlein purpura (HSP) is the most common vasculitis in children. It is a disorder of the inflammatory cascade leading to immunoglobulin A deposition and leukocytoclastic vasculitis of small vessels of skin, kidneys, joints, and gastrointestinal (GI) tract. A wide variety of GI manifestations are seen in ?50% to 75% of patients with HSP. Diffuse colicky abdominal pain is the most common GI symptom. The small bowel is the most frequently involved GI site. Intussusception is rare but is the most common surgical complication. We report the case of a 2-year-old girl with a 5-day history of abdominal pain followed by a palpable purpuric rash. Her urinalysis, complete blood cell count, and tests of renal function were normal. An acute abdominal series was unremarkable initially, and abdominal ultrasound imaging showed ascites and thickened small bowel loops. She was diagnosed with HSP. The abdominal pain worsened, and an abdominal computed tomography scan demonstrated distal small bowel wall thickening and pneumatosis intestinalis in the descending colon. She was started on total parenteral nutrition and antibiotics and placed on bowel rest. She was given 2 mg/kg of intravenous immunoglobulin. Her abdominal pain gradually improved over the next week, and a repeat computed tomography scan showed significant improvement of the small bowel wall thickening and pneumatosis. The purpuric rash improved, and her abdominal pain resolved. We report a case of HSP and pneumatosis intestinalis, an association that has not been reported previously. PMID:25157006

  8. Gastrointestinal manifestations of Henoch-Schonlein purpura: A report of two cases

    PubMed Central

    Prathiba Rajalakshmi, Parameswaran; Srinivasan, Kalyanasundaram

    2015-01-01

    Henoch-Schonlein purpura (HSP) is a small vessel vasculitis mediated by type III hypersensitivity with deposition of IgA immune complex in the walls of vessels. It is a multi-system disorder characterized by palpable purpura, arthritis, glomerulonephritis and gastrointestinal manifestations and commonly occurs in children and young adults. The patients with gastrointestinal involvement usually present with colicky abdominal pain, vomiting and melena. The imaging findings include multifocal bowel thickening with mucosal hyperenhancement, presence of skip areas, mesenteric vascular engorgement, with involvement of unusual sites like stomach, duodenum and rectum. These imaging findings in a child or young adult with appropriate clinical findings could suggest HSP. PMID:25825636

  9. Pneumococcal sepsis-induced purpura fulminans in an asplenic adult patient without disseminated intravascular coagulation.

    PubMed

    Saraceni, Christine; Schwed-Lustgarten, Daniel

    2013-12-01

    Acute perturbations in the hemostatic balance of anticoagulation and procoagulation antecede the manifestation of purpura fulminans, a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin. Hallmarks include small vessel thrombosis, tissue necrosis and disseminated intravascular thrombosis. The course may be rapidly fulminant resulting in multiorgan failure with thrombotic occlusion of the vasculature, leading to distal extremity ischemia and necrosis. Depletion of protein C (PC) has been emphasized in the pathogenesis. Early intravenous antibiotic administration and hemodynamic support are cornerstones in management. Herein, we report a case of pneumococcal sepsis-induced purpura fulminans limited to the skin in an asplenic adult patient without the development disseminated intravascular coagulation. PMID:24185261

  10. Henoch-Schönlein purpura without systemic involvement beginning with acute scrotum and mimicking torsion of testis.

    PubMed

    Verim, Levent; Cebeci, Filiz; Erdem, M Remzi; Somay, Adnan

    2013-03-01

    Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children. Typical presentations of HSP are palpable purpura of the small vessels in the hips and lower limbs, abdominal pain, arthritis, and hematuria. Scrotal involvement manifested by the presence of scrotal pain and swelling during the course of the disease is rarely seen. HSP without systemic involvement with acute scrotum mimicking testicular torsion is even rare in the medical literature. In most cases, patients with this disease achieve complete recovery. Herein, we report an interesting HSP case with skin symptoms but without systemic involvement and then progression to acute scrotum resembling torsion of testis. PMID:23695408

  11. Henoch-Schönlein purpura with uveitis: an unusual case and review of literature.

    PubMed

    Kaur, Sharandeep; Maheshwari, Anu; Aneja, Satinder; Seth, Anju; Beri, Sarita; Agarwal, Shilpi; Garg, Taru

    2012-12-01

    Henoch-Schönlein purpura (HSP) is a small vessel vasculitis with IgA dominant immune complex deposition. It is characterized by a triad of palpable purpura (without thrombocytopenia), abdominal pain and arthritis. Uveitis is rarely associated with HSP with only 3 cases reported in literature. All these cases were in adult population and were associated with nephritis. However, this association is not reported in paediatric age group. We are reporting a case of an 11-year-old child of recurrent HSP with uveitis. PMID:21918898

  12. Gastrointestinal manifestations of Henoch-Schonlein purpura: A report of two cases.

    PubMed

    Prathiba Rajalakshmi, Parameswaran; Srinivasan, Kalyanasundaram

    2015-03-28

    Henoch-Schonlein purpura (HSP) is a small vessel vasculitis mediated by type III hypersensitivity with deposition of IgA immune complex in the walls of vessels. It is a multi-system disorder characterized by palpable purpura, arthritis, glomerulonephritis and gastrointestinal manifestations and commonly occurs in children and young adults. The patients with gastrointestinal involvement usually present with colicky abdominal pain, vomiting and melena. The imaging findings include multifocal bowel thickening with mucosal hyperenhancement, presence of skip areas, mesenteric vascular engorgement, with involvement of unusual sites like stomach, duodenum and rectum. These imaging findings in a child or young adult with appropriate clinical findings could suggest HSP. PMID:25825636

  13. Stroke and skin rash: A rare case of Henoch-Schonlein purpura.

    PubMed

    Ghosh, Kaushik; Chatterjee, Atri; Sau, Jyoti Tanmay; Dey, Sandip

    2012-10-01

    Henoch-Schonlein purpura (HSP) is a small vessel vasculitis that is rare in adults. Here, we present a case of a woman who presented with palpable purpura, abdominal pain, arthritis and ischemic stroke. The patient met the diagnostic criteria of HSP. However, cerebrovascular disease is reported as an uncommon, yet fatal, complication of HSP. The patient responded to aggressive immunosuppression with pulses of corticosteroids and cyclophosphamide. In the absence of an established protocol of treatment of such neurologic emergency in HSP patients, this report demonstrates a successful outcome. PMID:23349600

  14. Factor XIII deficiency in Henoch-Schönlein purpura - report on two cases and literature review.

    PubMed

    Hogendorf, Anna; M?ynarski, Wojciech

    2014-01-01

    Factor XIII (FXIII) deficiency is a rare, inherited or acquired coagulation disorder that potentially precipitates fatal haemorrhage. We report two consecutive pediatric patients with Henoch-Schönlein purpura (HSP) and symptomatic decrease in FXIII. The possible FXIII deficiency should be kept in mind by every doctor taking care of patients with HSP, in spite of normal value of routine coagulation tests. PMID:25182395

  15. Group A Escherichia coli-Related Purpura Fulminans: an Unusual Manifestation Due to an Unusual Strain?

    PubMed Central

    Amara, Marlène; Bonacorsi, Stéphane; Bedel, Jérôme; Mira, Jean-Paul; Laurent, Virginie; Socha, Koryna; Bruneel, Fabrice; Pangon, Béatrice; Bédos, Jean-Pierre

    2014-01-01

    We describe an exceptional case of life-threatening group A Escherichia coli-induced purpura fulminans. Genotyping of common polymorphisms in genes involved in innate immunity or coagulation did not reveal known susceptibility to such a manifestation. Genetic analysis of the strain revealed an unusual conserved virulence plasmidic region, pointing out its potential virulence. PMID:25232165

  16. Occurrence of thrombosis in congenital thrombocytopenic disorders: a critical annotation of the literature.

    PubMed

    Girolami, Antonio; Sambado, Luisa; Bonamigo, Emanuela; Vettore, Silvia; Lombardi, Anna M

    2013-01-01

    Patients with a low platelet count are prone to bleeding. The occurrence of a thrombotic event in congenital thrombocytopenic patients is rare and puzzling. At least nine patients with Glanzmann thrombasthenia have been reported to have had a thrombotic event, eight venous and one arterial (intracardiac, in the left ventricle). On the contrary, three patients with Bernard-Soulier syndrome have been shown to have had arterial thrombosis (myocardial infarction) but no venous thrombosis. Finally, seven patients with the familiar macrothrombocytopenia due to alterations of the MYH9 gene have been reported to have had thrombosis (five myocardial infractions, one ischemic stroke, one deep vein thrombosis and one portal vein thrombosis). The significance of these findings is discussed with particular emphasis on the discrepancy between venous and arterial thrombosis seen in patients with Glanzmann thrombasthenia and Bernard-Soulier syndrome. PMID:23037321

  17. Henoch-Schonlein Purpura—A Case Report and Review of the Literature

    PubMed Central

    Sohagia, Amit B.; Gunturu, Srinivas Guptha; Tong, Tommy R.; Hertan, Hilary I.

    2010-01-01

    We describe a case of an adolescent male with Henoch-Schonlein purpura (HSP), presenting with cutaneous and gastrointestinal manifestations. Endoscopy revealed diffuse ulcerations in the stomach, duodenum, and right colon. Biopsies revealed a leukocytoclastic vasculitis in the skin and gastrointestinal tract. Steroid therapy led to complete resolution of the symptoms. HSP is the most common childhood vasculitis, and is characterized by the classic tetrad of nonthrombocytopenic palpable purpura, arthritis or arthralgias, gastrointestinal and renal involvement. It is a systemic disease where antigen-antibody (IgA) complexes activate the alternate complement pathway, resulting in inflammation and small vessel vasculitis. Mild disease resolves spontaneously, and symptomatic treatment alone is sufficient. Systemic steroids are recommended for moderate to severe HSP. The prognosis depends upon the extent of renal involvement, which requires close followup. Early recognition of multiorgan involvement, especially outside of the typical age group, as in our adolescent patient, and appropriate intervention can mitigate the disease and limit organ damage. PMID:20508739

  18. Stenosing ureteritis in Henoch-Schönlein purpura: report of two cases.

    PubMed

    Kasahara, Katsuaki; Uemura, Osamu; Nagai, Takuhito; Yamakawa, Satoshi; Nakano, Masaru; Iwata, Naoyuki

    2015-04-01

    Stenosing ureteritis (SU), a rare complication of Henoch-Schönlein purpura (HSP), typically presents with severe symptoms. We report the cases of two HSP patients presenting with gross hematuria, blood clotting, and colicky flank pain, followed by purpura on the lower extremities. Early-stage ultrasonography indicated hydronephrosis, thickened renal pelvic mucous membrane, and ureteral dilatation (UD), suggesting HSP complicated with SU. After early SU treatment with prednisolone, kidney function, thickened renal pelvic mucous membrane, and UD progressively normalized and the pain gradually disappeared. Regular ultrasonography of HSP patients from the onset of gross hematuria can be useful to detect early SU and facilitate conservative therapy with prednisolone. Diagnosis of SU can be easily missed by assuming HSP nephritis, particularly owing to the non-specific symptoms. Common characteristics as well as treatment methods and prognosis of SU are given in the literature review. PMID:25868951

  19. Terminal ileitis induced by Henoch-Schonlein purpura that presented as acute appendicitis: a case report.

    PubMed

    Fan, Zhe; Tian, Xiaofeng; Pan, Jiyong; Li, Yang; Zhang, Yingyi; Jing, Huirong

    2015-02-01

    Henoch-Schonlein purpura (HSP) is a self-limited autoimmune disease, the cause of which is not clear. Gastrointestinal involvement is often the main symptom of HSP. We report an unusual and rare case in a patient who was diagnosed with HSP. This is the second report of terminal ileitis induced by HSP that presented as acute appendicitis. We report a 21-year-old man who presented with right lower abdominal pain, and was diagnosed with acute appendicitis. Terminal ileitis was diagnosed intraoperatively, and when a rash occurred postoperatively, the final diagnosis was HSP. When the rash occurred, HSP was diagnosed and methylprednisolone was administered for 5 days. The diagnosis of HSP is difficult to establish, especially when the purpura occurs after gastrointestinal involvement; thus, abdominal pain should not be ignored and HSP should be considered. PMID:25654396

  20. Granulomatosis with polyangiitis presenting as Henoch-Schönlein purpura in children.

    PubMed

    Bui, Tuan; Chandrakasan, Shanmuganathan; Poulik, Janet; Fathalla, Basil M

    2013-06-01

    Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, in children is an uncommon chronic organ- and life-threatening systemic vasculitis that may share at time of initial presentation a number of clinical features in common with Henoch-Schönlein purpura (HSP), a very common and comparatively benign form of childhood vasculitis. Diagnosis of GPA requires a high index of suspicion, and antineutrophil cytoplasmic antibody tests along with tissue biopsy are helpful tools for diagnosis. We report 2 patients with GPA masqueraded as HSP at time of initial presentation. Both patients presented with nonthrombocytopenic purpura on lower extremities, in addition to abdominal pain, and/or microscopic hematuria and fulfilled both the American College of Rheumatology and the Pediatric Rheumatology European Society classification criteria for HSP. Both patients eventually developed significant renal and pulmonary disease and were diagnosed with GPA. We aim to raise awareness of such atypical presentations of GPA to avoid delayed management. PMID:23669806

  1. Severe hemorrhagic bullous lesions in Henoch Schonlein purpura: three pediatric cases and review of the literature.

    PubMed

    Trapani, Sandra; Mariotti, Paola; Resti, Massimo; Nappini, Lido; de Martino, Maurizio; Falcini, Fernanda

    2010-08-01

    Henoch Schonlein purpura (HSP) is a small-sized blood vessels vasculitis, resulting from immunoglobulin A-mediated inflammation. It is the most common acute systemic vasculitis in childhood and mainly affects skin, gastrointestinal tract, joints and kidney. Skin lesions, usually presenting as erythematous maculopapules, petechiae, and purpura, often involve lower extremities and buttocks, but may also extend to the upper extremities, face and trunk. Conversely to adults, hemorrhagic bullous evolution has been seldom described in childhood. The pressure is likely a factor into the pathogenesis of bullae. We report on three new pediatric cases of HSP with hemorrhagic bullous skin lesions, and a review of the literature. Bullous evolution represents an unusual, but well-recognized cutaneous manifestation that may be a source of diagnostic dilemma, but does not seem to have any prognostic value in the outcome of HSP. PMID:19609528

  2. Korean Herbal Medicine for Treating Henoch-Schonlein Purpura with Yin Deficiency: Five Case Reports

    PubMed Central

    Kim, Sung-Kyun; Ryu, Seung-Seon; Park, Sunju; Park, Sang-Kyun; Choi, Woo-Jin; Sun, Seung-Ho

    2014-01-01

    Objectives: The purpose of this study is to report the clinical effect of Korean medicine (KM) treatment for Henoch-Schonlein purpura (HSP). Methods: Five HSP patients who demonstrated a Yin deficiency and who had a history of a previous upper respiratory tract infection were included in this study. Four patients had arthritis and three had severe stomachache. One of them appeared to have proteinuria and hematuria before starting KM treatment. Results: All patients were improved with only herbal medicine, Jarotang (JRT). Purpura in the lower extremities and abdominal pain, which were not treated by using a corticosteroid, disappeared and had not recurred after 6 months. Conclusion: These cases indicate that JRT may be effective in treating HSP in patients who demonstrate Yin deficiency, even though the number of cases was limited to five. PMID:25780723

  3. An interesting perioperative rendezvous with a case of Henoch-Schonlein purpura

    PubMed Central

    Kurdi, Madhuri S.; Deva, Radhika S.; Theerth, Kaushic A.

    2014-01-01

    Henoch-Schonlein purpura (HSP) is an autoimmune, multisystem, acute vasculitis of childhood commonly involving the skin, gut, joints and the kidneys. Fatal complications involving various systems can occur in this disease and careful perioperative management is advocated. We report here the occurrence of postoperative bradycardia and the successful perioperative management of a 12-year-old boy with HSP for diagnostic laparoscopy. PMID:25886345

  4. Neutrophil activation, protein oxidation and ceruloplasmin levels in children with Henoch-Schönlein purpura

    Microsoft Academic Search

    Ayd?n Ece; Selvi Kelekçi; A?k?n Hekimo?lu; Halil Kocamaz; Hasan Bal?k; ?lyas Yolba?; Özcan Erel

    2007-01-01

    The aim of this study was to investigate the role of neutrophil activation, protein oxidation and ceruloplasmin (CLP) in the\\u000a pathogenesis of Henoch-Schönlein purpura (HSP), which has not been investigated previously. Serum activities of myeloperoxidase\\u000a (MPO) and arylesterase (ARYL) and levels of free thiol groups, CLP and total oxidant status (TOS) were measured in 29 children\\u000a with HSP at the

  5. Goodpasture syndrome during the course of a Schönlein-Henoch purpura

    Microsoft Academic Search

    Luis Carreras; Rafael Poveda; Jordi Bas; Mariona Mestre; Inés Rama; Marta Carrera

    2002-01-01

    Two months after surgical resection of a bronchogenic carcinoma, a 69-year-old patient presented with Schönlein-Henoch purpura with kidney involvement followed by pulmonary hemorrhage. The presence of an IgA linear pattern on the kidney biopsy specimen and circulating anti-glomerular basement membrane (GBM) IgA antibodies led to the diagnosis of Goodpasture syndrome, which implies the possibility that the well-known pulmonary involvement during

  6. Guillain-Barre syndrome in an adult patient with Henoch-Schonlein purpura

    PubMed Central

    Aggarwal, Puneet; Sahoo, Ratnakar; Gadpayle, A K; Kumar, Gunjan

    2013-01-01

    A 42-year-old man presented with pain in the abdomen, massive haematemesis and rashes over the body and development of bilateral lower limb weakness the next day. The patient was later diagnosed with Guillain-Barre syndrome with Henoch-Schonlein purpura. He was treated with intravenous immunoglobulins. At 3?months of follow-up and rehabilitation, patient showed complete recovery from weakness. PMID:23559644

  7. Spontaneous Bacterial Peritonitis and Henoch-Schönlein Purpura in a Patient with Liver Cirrhosis

    PubMed Central

    Gupta, Neil; Kim, Joyce; Njei, Basile

    2015-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel systemic vasculitis, predominantly affecting children, characterized by a tetrad of manifestations, specifically palpable purpura, arthralgia, abdominal pain, and renal disease. HSP in the adult population is rare, and no case has been described of HSP in liver cirrhosis with spontaneous bacterial peritonitis (SBP). We present the case of a 58-year-old male with liver cirrhosis, who was subsequently diagnosed with SBP and later HSP. In this patient, the diagnosis of HSP was demonstrated clinically by his palpable purpura, diarrhea, hematuria, and abdominal pain and confirmed pathologically by his renal and skin biopsies demonstrating leukocytoclastic vasculitis and IgA complexes. We believe that this is an example of altered IgA processing in cirrhosis leading to the development of IgA immune complexes and ultimately HSP. The patient additionally had SBP, which may have increased his risk for developing HSP given antigen processing by mucosa-associated lymphoid tissues leading to immune complex deposition, which may not have been effectively cleared in the context of his liver disease. The patient unfortunately died of gastrointestinal hemorrhage, which is unclear to be due to his underlying cirrhosis or a gastrointestinal manifestation of HSP itself.

  8. Differences in clinical manifestations and outcomes between adult and child patients with Henoch-Schönlein purpura.

    PubMed

    Kang, Yoon; Park, Jin-su; Ha, You-Jung; Kang, Mi-il; Park, Hee-Jin; Lee, Sang-Won; Lee, Soo-Kon; Park, Yong-Beom

    2014-02-01

    We aimed to investigate differences in clinical manifestations and outcomes between adult and child patients with Henoch-Schönlein purpura (HSP), and to analyze the factors associated with poor prognosis for HSP nephritis. This retrospective 10-yr study enrolled 160 patients with HSP who visited Severance Hospital. Purpura was mostly detected in lower extremities, but purpura in upper extremities was more frequently observed in adults than children (41.7% vs 19.3%). Children had a greater frequency of arthralgia (55.4% vs 27.1%), while adults had a greater frequency of diarrhea (20% vs 1.6%). Anemia, elevated C-reactive protein, and level of IgA were more frequently observed in adults (25% vs 7.1%, 65.6% vs 38.4%, 26.3% vs 3.5%). Renal involvement in adults was more severe than in children (79.2% vs 30.4%). Chronic renal failure showed a significant difference in outcomes of HSP between adults (10.4%) and children (1.8%) after a follow up period of an average of 27 months. Furthermore, renal insufficiency at diagnosis was significantly related to the progression to chronic renal failure. Our results showed several differences in the clinical features of HSP between adults and children. Adults with HSP had a higher frequency of renal insufficiency and worse renal outcomes than children. Renal insufficiency at diagnosis might be of predictive value for the progression to chronic renal failure in HSP patients. PMID:24550645

  9. An atypical case of Henoch-Shonlein purpura in a young patient: treatment of the skin lesions with hyaluronic acid-based dressings.

    PubMed

    Carella, Sara; Maruccia, Michele; Fino, Pasquale; Onesti, Maria Giuseppina

    2013-01-01

    Henoch-Shönlein purpura (HSP) is an acute, self-limited, systemic, small vessel vasculitis, that induces skin lesions, arthritis and abdominal pain. Palpable purpura is the most common manifestation in pediatric patients with HSP. We present an atypical case of HSP in a young patient and report successful treatment of the atypical skin lesions, while avoiding surgery. PMID:23239864

  10. Pravastatin-induced rhabdomyolysis and purpura fulminans in a patient with chronic renal failure

    PubMed Central

    Kato, Kazuya; Onodera, Kazuhiko; Iwasaki, Yoshiaki; Matsuda, Minoru; Kawakami, Takako; Higuchi, Mineko; Kato, Kimitaka; Kato, Yurina; Taniguchi, Masahiko; Furukawa, Hiroyuki

    2015-01-01

    Introduction Rhabdomyolysis associated with the use of pravastatin has been demonstrated to be a rare but potentially life-threatening adverse effect of statins. Here, we report a rare case of rhabdomyolysis and purpura fulminans in a patient who had used pravastatin and developed chronic renal failure (CRF) necessitating the initiation of dialysis. Presentation of case We present the case of an 86-year-old man with chronic kidney disease (CKD) treated with dialysis who was admitted with back pain. He was prescribed and took pravastatin for almost 3 years to treat hyperlipidemia. He received hemodialysis therapy 7 times prior to presentation. Laboratory values included a serum creatine concentration of 6.6 mg/dl and a creatinine phosphokinase (CPK) concentration of 2350 IU/L. An abdominal computed tomography scan showed swollen muscles with reduced muscle density and air density in the multifidus muscle. Two days after admission, he had large, tender ecchymotic lesions and purpuric progressive skin necrosis over the back, abdomen, and upper and lower extremities. The patient died 6 days after the initial admission due to disseminated intravascular coagulation (DIC). Based on these findings and the clinical history, a diagnosis of pravastatin-induced rhabdomyolysis and purpura fulminans was made. Discussion The long-term use of statin therapy and the initiation of dialysis therapy due to ESRD, followed by a rapid onset of rhabdomyolysis within 6 days, is indicative of an elevated statin concentration. Conclusion We report an extremely rare case of pravastatin-induced rhabdomyolysis and purpura fulminans with DIC in a patient with CRF. PMID:25644555

  11. Acquired amegakaryocytic thrombocytopenia purpura and eosinophilic fasciitis: a long relapsing and remitting course.

    PubMed

    Chaudhary, Uzair B; Eberwine, Stephen F; Hege, Kristen M

    2004-03-01

    Acquired amegakaryocytic thrombocytopenia purpura (AATP) is a rare disorder of unclear etiology characterized by severe thrombocytopenia, preservation of erythroid and myeloid cell lines, and absence of megakaryocytes in the bone marrow. We report herein a patient who developed eosinophilic fasciitis preceding a diagnosis of AATP. Longitudinal follow-up and treatment of this individual show a relapsing and remitting disease course which appears closely related to the dosing of cyclosporine. Later in the treatment course, dosing of anti-thymocyte globulin (ATG) appeared to have important beneficial contributions in the management of this patient's disease. PMID:14978695

  12. Henoch-Schönlein Purpura with thoraco-lumbar spine involvement precipitated by trampoline jumping

    Microsoft Academic Search

    Alexander K. C. Leung

    1995-01-01

    A nine-year-old boy with Henoch-Schönlein Purpura (HSP) presented with an arthropathy of the thoraco-lumbar spine. The boy\\u000a played on a trampoline for several days before the onset of the low-back pain. The vascultic rash of HSP is recognized to\\u000a be pressure-dependent. The authors speculate that the arthropathy of HSP is also pressure-dependent and that the low back\\u000a pain in this

  13. Treatment of progressive pigmented purpura with oral bioflavonoids and ascorbic acid: An open pilot study in 3 patients

    Microsoft Academic Search

    U. Reinhold; S. Seiter; S. Ugurel; W. Tilgen

    1999-01-01

    Background: Bioflavonoids and ascorbic acid have been shown to increase capillary resistance and to mediate potent antioxidative radical scavenging activities. Objective: We evaluated the clinical effect of oral bioflavonoids and ascorbic acid in patients with chronic progressive pigmented purpura (PPP). Methods: In an open pilot study, oral rutoside (50 mg twice a day) and ascorbic acid (500 mg twice a

  14. A rare presentation of Henoch-Schönlein purpura and myocardial infarction at the 5th decade of life.

    PubMed

    Rajan, Rajesh; Joseph, Peter K; Govindan, Vijayaraghavan

    2013-06-01

    Henoch-Schönlein purpura is an IgA-mediated, autoimmune, hypersensitivity vasculitis of childhood that results in a triad of symptoms, including a purpuric rash occurring on the lower extremities, abdominal pain or renal involvement, and arthritis. However, any of the triad may be absent, which often leads to a confusion in diagnosing the condition. Although the cause is unknown, Henoch-Schönlein purpura (HSP) is often associated with infectious agents, such as group A streptococci and mycoplasma. It has also been associated with food reactions, exposure to cold, insect bites, and drug allergies. The treatment is supportive and needs close followup of renal status. This report describes a rare presentation of Henoch-Schönlein purpura with coronary vasculitis which leads to myocardial infarction at the age of 53. Henoch-Schönlein purpura was diagnosed on the basis of no infection, accelerated ESR (35 mm/h), normal platelet count, positive skin biopsy, proteinuria, and negative searches for rheumatoid factor (RF), antinuclear antibody (ANA), antineutrophil cytoplasmic antibodies (ANCA), and anti-dsDNA. PMID:24265897

  15. Purpura and fillers: a review of pre-procedural, intra-procedural, and post-procedural considerations.

    PubMed

    Schlesinger, Todd E; Cohen, Joel L; Ellison, Sarah

    2013-10-01

    Injectable aesthetic fillers are associated with the common and expected side effect of purpura or bruising. There are pre-procedural, intra-procedural and post-procedural considerations that can potentially minimize bruising. Traditional and newer techniques are discussed in this review and the benefits and risks of each technique will be provided. PMID:24085049

  16. [Henoch-Schönlein purpura with late-onset necrotising glomerulonephritis--a case report].

    PubMed

    Mitrovi?, Joško; Pukši?, Silva; Horvati?, Ivica; Tišma, Vesna Sredoja; Bulimbaši?, Stela; Morovi?-Vergles, Jadranka

    2014-01-01

    Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, while it is rare in adults. Typical clinical manifestations include palpable purpura without thrombocytopenia and/or coagulopathy, arthritis/arthralgia, abdominal pain, and/or renal involvement. In adulthood the disease tends to be more serious than in children, with renal manifestations developing over a period of several days to one month after initial symptoms. In this article we present a 22-year-old female patient with cutaneous vasculitis and arthralgia, in whom renal disease developed 8 weeks after disease onset with microscopic hematuria and proteinuria in urinalysis. Renal biopsy subsequently performed revealed focal necrotising glomerulonephritis with IgA deposits. The patient was treated with high dose methylprednisolone followed by gradual tapering, which induced complete remission of the disease. In conclusion, patients with HSP should be carefully monitored for systemic involvement, since serious renal disease can develop even as late as two months after disease onset. PMID:25509835

  17. Renal manifestations in Henoch-Schönlein purpura: a 10-year clinical study.

    PubMed

    Chang, Wen-Liang; Yang, Yao-Hsu; Wang, Li-Chieh; Lin, Yu-Tsan; Chiang, Bor-Luen

    2005-09-01

    Henoch-Schönlein purpura (HSP) is an IgA-mediated systemic small vessel vasculitis of childhood. It is characterized by the symptoms including nonthrombocytopenic purpura, abdominal pain, hematuria/proteinuria, and arthargia/arthritis. We conducted a retrospective study of 261 patients diagnosed with HSP from December 1991 to December 2001. Of the 261 patients, fifty-three (20.3%) developed renal manifestations after onset of the disease. Two patients developed nephrotic syndrome. Four patients had group A beta-hemolytic streptococcal pharyngitis and subsequent depressed serum C3 concentration typical of post streptococcal glomerulonephritis. During the study period, the renal survival rate after disease onset was 100%. The prognosis of renal involvement was better than reports from other series. In this study we also found factors associated with HSP nephritis; these included older age at onset, GI bleeding, and central nervous system involvement. The long-term morbidity of HSP is predominantly attributed to renal involvement. It is thus recommended that patients with HSP nephritis are followed for longer periods of time. PMID:15947991

  18. IgA vasculitis (Henoch-Shönlein purpura) in adults: Diagnostic and therapeutic aspects.

    PubMed

    Audemard-Verger, Alexandra; Pillebout, Evangeline; Guillevin, Loïc; Thervet, Eric; Terrier, Benjamin

    2015-07-01

    Immunoglobulin A (IgA) vasculitis, formerly called Henoch-Schönlein purpura, is an immune complex vasculitis affecting small vessels with dominant IgA deposits. Clinical manifestations mainly involve cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis. IgA vasculitis is more common among children than adults, with more severe disease in adults. Gastrointestinal and renal involvements represent the principal causes of morbidity and mortality in adults. Factors associated with long-term end-stage renal disease (ESRD) include baseline renal function impairment and baseline proteinuria >1 or 1.5 g/day, and on renal biopsy degree of interstitial fibrosis, sclerotic glomeruli and fibrinoid necrosis. Management of IgA vasculitis in adults is rendered difficult for clinicians because of the absence of correlation between initial presentation and long-term renal outcome, and the possible occurrence of spontaneous remission in patients with severe presentation or, in contrast, possible evolution to ESRD in patients with mild symptoms. Treatment is often symptomatic because disease course is usually benign. Treatment of severe involvement, including severe gastrointestinal complications or proliferative glomerulonephritis, remains controversial, with no evidence that corticosteroids or immunosuppressive agents improved long-term outcome. Prospective, randomized, controlled trials are thus needed to analyze the benefit-risk ratio of such treatments. PMID:25688001

  19. I MMUNE T HROMBOCYTOPENIC P URPURA

    Microsoft Academic Search

    B. C INES; V ICTOR S. B LANCHETTE

    MMUNE thrombocytopenic purpura is an auto- immune disorder characterized by a low platelet count and mucocutaneous bleeding. The estimat- ed incidence is 100 cases per 1 million persons per year, and about half of these cases occur in children. 1-3 Im- mune thrombocytopenic purpura is classified as pri- mary or as secondary to an underlying disorder and as acute (of

  20. Thrombosis and priapism in a patient with Henoch-Schonlein purpura.

    PubMed

    Sari, Ismail; Akar, Servet; Secil, Mustafa; Birlik, Merih; Kefi, Aykut; Onen, Fatos; Celebi, Ilhan; Akkoc, Nurullah

    2005-08-01

    Henoch-Schönlein purpura (HSP) belongs to the category of systemic small-vessel vasculitis. Although long-term outcome is generally good, serious complications may occur. Thrombosis and priapism have been reported only as extremely rare complications of HSP. We describe a 37-year-old man who developed recurrent thrombotic events shortly after he had been diagnosed as having HSP. Although he had additional risk factors for thrombosis, such as prothrombin G20210A mutation and use of celecoxib before the last episode, temporal relation of the thrombotic attacks to the onset of HSP suggest that the disease itself may lead to a prothrombotic state. This case is the first adult HSP patient with priapism, which probably developed secondary to thrombosis of the dorsal penile vein. PMID:16133584

  1. [The case of Henoch-Schönlein Purpura associated with Blastocystis hominis].

    PubMed

    Tutanç, Murat; Silfeler, Ibrahim; Ozgür, Tümay; Motor, Vicdan Köksald?; Kurto?lu, Ahmet Ibrahim

    2013-01-01

    Blastocystis hominis (B. hominis) is a parasite that often causes gastrointestinal symptoms in patients with immune deficiency and has a controversial pathogenicity in healthy people, although some symptoms are reported outside of the gastrointestinal system in healthy persons. Henoch-Schönlein Purpura (HSP) vasculitis is an acute autoimmune disease characterised by IgA storage of small vessels that is believed to include infectious factors in its aetiology. A 30-month follow-up with a boy diagnosed with HSP being treated with steroid therapy showed that he had recurrent symptoms within two days, and B. hominis was detected in the faecal analysis. His symptoms including rash, abdominal pain, and arthritis improved after treatment with steroid and co-trimaksazol. This paper is the first to present a case of HSP associated with B. hominis. PMID:23955912

  2. Advances in our understanding of the pathogenesis of Henoch-Schönlein purpura and the implications for improving its diagnosis.

    PubMed

    Park, Se Jin; Suh, Jin-Soon; Lee, Jun Ho; Lee, Jung Won; Kim, Seong Heon; Han, Kyoung Hee; Shin, Jae Il

    2013-12-01

    Henoch-Schönlein purpura (HSP) is a leukocytoclastic vasculitis classically characterized by palpable purpura, arthritis, abdominal pain and renal disease. In this article, we summarize our current understanding of the pathogenesis of HSP and the implications for improving its diagnosis. Although the pathogenesis of HSP is not fully understood yet, exciting new information has emerged in recent years, leading to a better understanding of its pathogenesis. Here, we discuss genetic predisposition, immunoglobulins with a particular emphasis on IgA1, activated complements, cytokines and chemokines, abnormal coagulation and autoantibodies in the underlying pathogenic mechanisms. Finally, diagnostic criteria for HSP developed by institutions such as the American College of Rheumatology and the European League against Rheumatism/Paediatric Rheumatology European Society were proposed to improve early detection and diagnosis. PMID:24215411

  3. A case of elderly-onset Crescentic Henoch-Schönlein purpura nephritis with hypocomplementemia and positive MPO-ANCA.

    PubMed

    Yu, Jung-Hee; Lee, Kyu-Beck; Lee, Jae Eun; Kim, Hyang; Kim, Kyungeun; Jang, Ki-Seok; Park, Moon Hyang

    2012-08-01

    Henoch-Schönlein purpura (HSP) is common in childhood and often self-limiting. There have been limited studies on elderly-onset HSP nephritis (HSPN). A 76-yr-old man was transferred to our hospital with a 1-month history of oliguria, abdominal pain, edema and palpable purpura in the legs. Three months ago, he was admitted to another hospital with jaundice, and consequently diagnosed with early common bile duct cancer. The patient underwent a Whipple's operation. Antibiotics were administrated because of leakage in the suture from the surgery. However, he showed progressive renal failure with edema and purpura in the legs. Laboratory investigations showed serum creatinine 6.4 mg/dL, 24-hr urine protein 8,141 mg/day, myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) 1:40 and C(3) below 64.89 mg/dL. Renal biopsy showed crescentic glomerulonephritis, as well as mesangial and extracapillary Ig A deposition. We started steroid therapy and hemodialysis, but he progressed to end-stage renal failure and he has been under maintenance hemodialysis. We describe elderly onset HSPN with MPO-ANCA can be crescentic glomerulonephritis rapidly progressed to end stage renal failure. PMID:22876066

  4. Variation in inpatient therapy and diagnostic evaluation of children with Henoch Schönlein purpura

    PubMed Central

    Weiss, Pamela F.; Klink, Andrew J.; Hexem, Kari; Burnham, Jon M.; Leonard, Mary B.; Keren, Ron; Localio, Russell; Feudtner, Chris

    2009-01-01

    Objective To describe variation regarding inpatient therapy and evaluation of children with Henoch Schönlein purpura (HSP) admitted to children’s hospitals across the United States. Study design We conducted a retrospective cohort study of children discharged with a diagnosis of HSP between 2000 and 2007 using inpatient administrative data from 36 children’s hospitals. We examined variation among hospitals in the use of medications, diagnostic tests, and intensive care services using multivariate mixed effects logistic regression models. Results During the initial HSP hospitalization (N=1,988), corticosteroids were the most common medication (56% of cases), followed by opioids (36%), NSAIDs (35%), and anti-hypertensives (11%). After adjustment for patient characteristics, hospitals varied significantly in their use of corticosteroids, opioids, and NSAIDs; the use of diagnostic abdominal imaging, endoscopy, laboratory testing, and renal biopsy; and the utilization of intensive care services. By contrast, hospitals did not differ significantly regarding administration of anti-hypertensives or performance of skin biopsy. Conclusions The significant variation identified may contribute to varying HSP clinical outcomes between hospitals, warrants further investigation, and represents a potentially important opportunity to improve quality of care. PMID:19643437

  5. Relationship between Immune Parameters and Organ Involvement in Children with Henoch-Schonlein Purpura

    PubMed Central

    Shao, Wen-xia; Shang, Shi-qiang; Mao, Jian-hua; Zhang, Ting; Shen, Hong-qiang; Zhao, Ning

    2014-01-01

    Henoch-Schonlein purpura (HSP) is the most common type of connective tissue diseases which increasingly occurs in children in recent years and its pathogenesis remains unclear. In order to explore the immune parameters and underlying pathogenesis mechanism of children with HSP, the study involved 1232 patients with HSP having different clinical symptoms and their laboratory indicators were evaluated. Th1/Th2 imbalance and overactivity of Th2 cells can cause increase in the synthesis and release of immunoglobulins in children with HSP. The number of red blood cells and white blood cells in urine was directly proportional to the level of IgA and inversely proportional to the level of serum complements (C3 and C4). Activation of these complements caused by immunoglobulin in patients with HSP plays an important role in renal injury. The urinary protein content in children with HSP along with proteinuria was positively correlated with IgE level, and IgE mediated type 1 hypersensitivity can cause increase in capillary permeability and weakened the charge barrier; hence, it could be considered as one of the causes of proteinuria in HSP. Additionally, the NK cells percentage was reduced and impaired immune function of NK cells were related to the immune injury of the digestive tract and kidney. PMID:25514176

  6. Elevated Serum Levels of Visfatin in Patients with Henoch-Schönlein Purpura

    PubMed Central

    Cao, Na; Chen, Tao; Li, Meng-Meng; Jiao, Xiao-Yan

    2014-01-01

    Background Henoch-Schönlein purpura (HSP) is an immune complex-mediated disease predominantly characterized by the deposition of circulating immune complexes containing immunoglobulin A (IgA) on the walls of small vessels. Although the pathogenesis of HSP is not yet fully understood, some researchers proposed that B-cell activation might play a critical role in the development of this disease. Objective To investigate the serum levels of visfatin (pre-B-cell colony-enhancing factor), B-cell-activating factor (BAFF), and CXCL13, and to analyze their association with disease severity. Methods The serum levels of visfatin, BAFF, and CXCL13 were measured by using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 43 patients with HSP and 45 controls. The serum levels of IgA anticardiolipin antibodies (ACA) were detected by using a double-antigen sandwich ELISA. Results Levels of visfatin but not BAFF and CXCL13 were significantly elevated in the sera of patients with HSP in the acute stage, and restored to normal levels in the convalescent stage. Furthermore, serum levels of visfatin were significantly higher in patients with HSP having renal involvement than in those without renal involvement. Serum levels of visfatin were correlated with the severity of HSP and serum concentration of ACA-IgA. Conclusion We show for the first time that the serum levels of visfatin are abnormally elevated in patients with HSP. Visfatin may be associated with the pathogenesis of HSP. PMID:24966628

  7. Predictive factors of relapse in adult with Henoch-Schönlein purpura.

    PubMed

    Byun, Ji-Won; Song, Hee-Jin; Kim, Lucia; Shin, Jeong-Hyun; Choi, Gwang-Seong

    2012-04-01

    Henoch-Schönlein purpura (HSP) is an IgA-mediated small vessel vasculitis with a predominant cutaneous involvement. We assessed adult patients with HSP to identify the clinical and histopathological features and evaluate predictive factors of relapse. We reviewed the records of 29 adult patients with HSP who presented at our department between 2002 and 2009. Adult HSP was confirmed by skin biopsy showing leukocytoclastic vasculitis and direct immunofluorescence showing IgA deposit. Among the 29 patients (15 men, 14 women; mean age 36.2 years old), renal involvement was initially found in 22 patients (75.9%). They were divided into 2 groups according to the presence or absence of relapse. We compared clinical and histopathologic differences between 15 patients with relapse and 14 patients without relapse. By univariate analysis, older age at onset, persistent rash, abdominal pain, hematuria, and underlying disease at the onset of HSP are significantly related to relapse. Among the histopathological variables, severity of leukocytoclasis and absence of IgM deposit on the vessel walls are significantly associated to relapsing disease (P < 0.05). Our results are significant, because, they may help to understand the predictive factors related to relapses of HSP in adults. Further studies are necessary to identify whether more aggressive treatment in adults with HSP with these predictive factors can prevent relapse and severe renal sequelae. PMID:22441366

  8. Self-organizing phenomena induced by LLLT in Henoch-Schoenlein purpura

    NASA Astrophysics Data System (ADS)

    Ailioaie, Laura; Ailioaie, C.

    2001-06-01

    Henoch-Schoenlein purpura is characterized by vasculitis of small vessels, particularly those of the skin, gastrointestinal tract, and kidney. Patients have characteristic purpuric skin rash plus all or some of the following: migratory polyarthralgias or polyarthritis, colicky abdominal pain, nephritis. Because until now there is no satisfactory treatment, we applied low level laser therapy (LLLT) in order to compare it with the classical therapy. Twenty-three children (2-15 years of age) have been treated at debut of the disease. They were randomly divided: group A (11 children) received LLLT; group B (12 children) was administrated classical therapy. Two GaAlAs diode lasers (670 nm and 830 nm) were used. The density of energy (4-8 J/cm2), irradiating frequency (2.4 Hz) was applied one session daily, using scanning technique under a special treatment protocol on cutaneous purpuric areas (20 sessions). The best results were obtained in laser group. Despite the complex medication, some patients from group B fell back into the former state after apparent improvement, and two children developed nephritis. The results could be explained by self-organization. LLLT is acting as a trigger factor causing certain systemic effects through circulating blood and a response of the entire immune system, by way of synergetic mechanisms.

  9. Adult Henoch-Schönlein purpura associated with small cell lung cancer: A case report and review of the literature.

    PubMed

    Zhang, Xue-DE; Yang, Shuan-Ying; Li, Wei; Ming, Zong-Juan; Hou, Yan-Li; Niu, Ze-Qun; Zhang, Yu-Ping

    2013-06-01

    The present study reports the case of a 53-year-old male who had been suffering from coughing and the presence of a blood-streaked sputum for >1 month. Chest computed tomography (CT) and a bronchoscopic brush smear were performed. The patient was subsequently diagnosed with small cell lung cancer (limited stage). The patient developed polyarthritis, abdominal pain, diarrhea and a purpuric rash at 14 days post thoracotomy surgery for lung cancer. Henoch-Schönlein purpura (HSP) was diagnosed based on the clinical symptoms. The patient received chemotherapy with steroid therapy, which resulted in complete remission of the HSP. PMID:23833668

  10. The first case of Henoch-Schonlein purpura associated with rosuvastatin: colonic involvement coexisting with small intestine.

    PubMed

    Gonen, Korcan Aysun; Erfan, Gamze; Oznur, Meltem; Erdogan, Cuneyt

    2014-01-01

    Henoch-Schönlein purpura (HSP) is a systemic vasculitis affecting small vessels. It is the most common systemic vasculitis in children, and is rare in adults. Serious gastrointestinal complications are more common in childhood. Infections and drugs are the most prominent factors in the aetiology. Wall thickening in segments of the small intestine is commonly seen in imaging studies in gastrointestinal system (GIS) involvement. Simultaneous involvement of small intestine and colon is rare. An HSP case involving small intestine and colon in an adult patient due to the use of rosuvastatin, an antihyperlipidaemic agent, is presented, and is first of its kind reported in the literature. PMID:24648473

  11. IgA and temperature dependent IgG complex formation in a patient with Waldenström's hypergammaglobulinaemic purpura.

    PubMed Central

    Roberts-Thomson, P J; Kemp, A S

    1980-01-01

    We describe a patient with hypergammaglobulinaemic purpura and show that the serum contains IgG and IgA immune complexes sedimenting between IgM and IgG on ultracentrifugation. The complexes containing IgG were markedly temperature dependent. A drop in temperature from 37 degrees C to 28 degrees C gave a seventeen-fold increase in the quantity of these complexes. This temperature dependency may be an important factor in localizing the major pathological manifestation of this disease to the skin. PMID:7389190

  12. IgG and IgA classes of anti-neutrophil cytoplasmic autoantibodies in a 13-year-old girl with recurrent Henoch-Schonlein purpura

    Microsoft Academic Search

    Jen-Jar Lin; Charles L. Stewart; Frederick J. Kaskel; Richard N. Fine

    1993-01-01

    We describe a 13-year-old girl with recurrent Henoch-Schonlein purpura whose symptoms were precipitated by upper respiratory tract infections. Her serum was positive for both IgG and IgA classes of anti-neutrophil cytoplasmic autoantibodies by immunofluorescence. The titers of both autoantibodies correlated with disease activity. The immunopathology underlying these findings is discussed.

  13. Polyarteritis nodosa and Henoch-Schönlein purpura nephritis in a child with familial Mediterranean fever: a case report.

    PubMed

    Girisgen, Ilknur; Sonmez, Ferah; Koseoglu, Kutsi; Erisen, Seda; Yilmaz, Dilek

    2012-02-01

    Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent self-limited attacks of fever accompanied by peritonitis, pleuritis, and arthritis. Approximately 5% of individuals with familial Mediterranean fever have been reported to have Henoch-Schonlein purpura and about 1% to have polyarteritis nodosa. A 7-year-old girl presenting with complaints of purpuric rash, abdominal pain, arthritis, hematuria, and proteinuria and having IgA depositions on renal biopsy was diagnosed as Henoch-Schönlein nephritis. She had a history of recurrent fever, abdominal and joint pain and M694 V compound homozygote mutation. Colchicine treatment was started for the diagnosis of FMF. When constitutional symptoms such as myalgia, weight loss, fatigue, fever, and hypertension were added to the clinical picture, the diagnosis of polyarteritis nodosa HSP was thought and confirmed by the demonstration of microaneurisms on renal arteries. There was no response to corticosteroid and cyclophosphamide treatments; however, the symptoms were rapidly and dramatically reduced after the administration of intravenous immunoglobulin. In conclusion, polyarteritis nodosa and Henoch-Schonlein purpura can be seen together with familial Mediterranean fever. It is also suggested that IVIG might be an important adjunct therapy in selected patients with polyarteritis nodosa, especially in the lack of response to steroids and immunsuppressive drugs. PMID:21259007

  14. Differences in Platelet Function In Patients with Acute Myeloid Leukaemia and Myelodysplasia Compared to Equally Thrombocytopenic Patients with Immune Thrombocytopenia

    PubMed Central

    Psaila, Bethan; Bussel, James B.; Frelinger, Andrew L.; Babula, Bracken; Linden, Matthew D.; Li, Youfu; Barnard, Marc R.; Tate, Chinara; Feldman, Eric J.; Michelson, Alan D.

    2011-01-01

    Background Severe thrombocytopenia is a major risk factor for haemorrhage, and yet platelet function and bleeding risk at low platelet counts are poorly understood because of limitations of platelet function testing at very low platelet counts. Objectives To examine and compare platelet function in severely thrombocytopenic patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) to patients with immune thrombocytopenia (ITP). Methods Whole blood flow cytometric measurement of platelet activation and platelet reactivity to agonists was correlated with the immature platelet fraction (IPF) and bleeding symptoms. Results Compared with patients with ITP, patients with AML/MDS had smaller platelets, lower IPF, and substantially lower platelet surface expression of activated GPIIb/IIIa and GPIb both with and without addition of ex vivo ADP or TRAP. In both ITP and AML/MDS, increased platelet surface GPIb on circulating platelets and expression of activated GPIIb/IIIa and GPIb on ex vivo activated platelets correlated with a higher IPF. Whereas platelet reactivity was higher for AML/MDS patients with bleeding than those with no bleeding, platelet reactivity was lower for ITP patients with bleeding than those with no bleeding. Conclusions AML/MDS patients have lower in vivo platelet activation and ex vivo platelet reactivity than patients with ITP. The proportion of newly-produced platelets correlates with the expression of platelet surface markers of activation. These differences might contribute to differences in bleeding tendency between AML/MDS and ITP. This study is the first to define differences in platelet function between AML/MDS patients and ITP patients with equivalent degrees of thrombocytopenia. PMID:21920014

  15. Expression of acid-sensing ion channels of gastric mucosa from patients with Henoch-Schönlein purpura.

    PubMed

    Yuan, Li-ping; Bo, Yan; Ming, Gui; Zhou, Qi-lian

    2012-04-01

    Acid-sensing ion channels (ASICs) are members of the voltage-insensitive, amiloride-sensitive degenerin/epithelial Na channel family of cation channels and have been shown to mediate pain associated with tissue acidosis after inflammation or injury; however, the expression and role of ASICs in gastrointestinal tract of Henoch-Schönlein purpura (HSP) patients were still uncertain. The present study was designed to examine the expression and localization of ASICs in gastric mucosa from patients with HSP using immunochemical techniques. The results showed that there was a significant increase in the mean relative optical density of ASIC2 and ASIC3 but not ASIC1a in the lining epithelium and glandular tubes of gastric mucosa from HSP patients with HSP. This finding suggested that ASICs may be related to the pathogenesis of gastrointestinal manifestations in patients with HSP. PMID:22157923

  16. A rare association of acute bacterial endocarditis with Henoch-Schönlein purpura (HSP) in an adult patient.

    PubMed

    Ilyas, Shahid; Salim, Sumera

    2014-12-01

    Henoch-Schönlein purpura (HSP) is a systemic, small vessel vasculitic disorder that mainly affects joint, skin, gastrointestinal tract and kidneys. It is primarily a disease of children that is typically self-limited, but 10 percent of cases occur in adults where features and outcomes may vary. The underlying pathogenesis of HSP remains unknown. We report a case of HSP that occurred with the onset of acute bacterial endocarditis (ABE) in an otherwise healthy 37-year-old Native American male. The patient presented with fevers, fatigue, abdominal pain and renal failure and was found to have acute left-sided staphylococcal endocarditis. He subsequently developed small bowel perforation and purpuric rash. Initially he was treated with broad spectrum antibiotics and small bowel resection. However, resolution of HSP and the associated signs and symptoms was only achieved after treatment with oral steroids and plasmapheresis. PMID:25571618

  17. Henoch–Schönlein purpura in a renal transplant recipient with prior IgA nephropathy following influenza vaccination

    PubMed Central

    McNally, Andrew; McGregor, David; Searle, Martin; Irvine, John; Cross, Nicholas

    2013-01-01

    Henoch–Schönlein purpura (HSP) is a systemic small-vessel leucocytoclastic vasculitis with deposition of immune complexes containing Immunoglobulin A (IgA). IgA Nephropathy (IgAN) is a glomerulonephritis caused by mesangial deposition of IgA. The onset of HSP, but not IgAN, has been linked to influenza vaccination. We report the first case of HSP with glomerular involvement, in a renal transplant recipient following influenza vaccination. The patient had prior end-stage renal failure (ESRF) secondary to IgAN, without clinical evidence of IgAN recurrence after transplantation. This is of clinical relevance as influenza vaccination is regarded safe, effective, and recommended after renal transplantation. Nephrologists should be aware of the potential for influenza vaccination to have adverse effects in renal transplant recipients, especially if the primary renal disease is HSP or IgAN.

  18. Intravenous dexamethasone followed by oral prednisolone versus oral prednisolone in the treatment of childhood Henoch-Schönlein purpura.

    PubMed

    Shin, Jae Il; Lee, Su Jin; Lee, Jae Seung; Kim, Kee Hyuck

    2011-11-01

    The aim of this study was to evaluate the effectiveness of intravenous corticosteroid therapy when Henoch-Schönlein purpura (HSP) patients are unable to tolerate oral medications due to abdominal pain. We retrospectively analyzed 111 children with a diagnosis of HSP (mean age 6.9 ± 2.3 years, male:female = 54:57) from the years 2000 to 2007. They were divided into two groups: 49 patients received only oral prednisolone (PL group) and 62 patients received oral prednisolone after intravenous dexamethasone (Dexa + PL group). Palpable purpura was seen in all 111 patients (100%), abdominal pain in 55 (50%), and arthralgia in 65 (59%). Dexa + PL group had significantly longer duration of fasting than PL group (0.7 ± 1.2 vs. 0.02 ± 0.1 days, P < 0.01) due to more severe and frequent abdominal pain (68 vs. 27%, P < 0.01). Intravenous dexamethasone resulted in the rapid resolution of abdominal pain or arthralgia in all patients without major complications. However, the development of nephritis (21% in PL group versus 32% in Dexa + PL group, P = 0.098), the number of relapse (4 vs. 11%, P = 0.167), and persistent nephritis at last follow-up (12 vs. 16%, P = 0.563) were not different between the two groups despite more severe symptoms in Dexa + PL group. Intravenous dexamethasone followed by oral prednisolone may be a useful and effective therapeutic strategy in HSP children who cannot tolerate oral medications due to severe abdominal pain. PMID:20464400

  19. How Is Thrombocytopenia Diagnosed?

    MedlinePLUS

    ... Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Aplastic Anemia Blood Transfusion Disseminated Intravascular Coagulation Immune Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link ...

  20. Haematology and neurology

    Microsoft Academic Search

    Steven Austin; Hannah Cohen; Nick Losseff

    2007-01-01

    This review aims to update the reader on advances in the understanding of haematological conditions that may arise in neurological practice. Thrombophilia, antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, sickle cell and clonal disorders associated with neuropathy are discussed.

  1. What Causes Excessive Blood Clotting?

    MedlinePLUS

    ... blood clots. Thrombotic Thrombocytopenic Purpura and Disseminated Intravascular Coagulation Two rare, but serious conditions that can cause ... PURR-purr-ah), or TTP, and disseminated intravascular coagulation (ko-ag-u-LA-shun), or DIC. TTP ...

  2. Hemostatic Function and Transfusion Efficacy of Apheresis Platelet Concentrates Treated with Gamma Irradiation in Use for Thrombocytopenic Patients

    PubMed Central

    Zhu, Mei; Xu, Wei; Wang, Bao-Long; Su, Hong

    2014-01-01

    Summary Background During the transfusion of blood components, the transfer of allogeneic donor white blood cells (WBCs) can mediate transfusion-associated graft-versus-host disease (TA-GVHD). To minimize the reaction, exposure of blood products to gamma irradiation is currently the standard of care. The aim of our study was to evaluate and compare hemostatic function, transfusion efficacy, and safety of gamma-irradiated single-donor apheresis platelet concentrates (PCs) and of conventional non-irradiated PCs in patients with chemotherapy-induced thrombocytopenia. Methods 20 double-dose single-donor leukoreduced PCs were split in two identical units; one was gamma-irradiated with 25 Gy (study arm A) and the other remains non-irradiated (study arm B). Both units were stored under equal conditions. Hematologic patients were randomly assigned to receive gamma-irradiated or conventional non-irradiated PCs. Hemostatic function was evaluated by thrombelastography (TEG). TEG measurements were taken pre transfusion and 1 and 24 h post transfusion. TEG profiles were measured, noting the time to initiate clotting (R), the angle of clot formation (?), and the maximum amplitude (clot strength (MA)). Whole blood samples were collected from these thrombocytopenic patients at 1 and 24 h for PLT count increments (CIs) and corrected count increments (CCIs) with assessments of transfusion efficacy. Time to next PLT transfusion, transfusion requirement of RBCs, active bleeding, and adverse events (AEs), were analyzed. Results No differences could be found in hemostatic function parameters (MA, R, and ?) between study arms A and B (all p values > 0.096) pre transfusion as well as 1 and 24 h post transfusion. No differences between study arms A and B were observed for mean (± standard deviation (SD)) 1-hour CCI (12.83 ± 6.33 vs. 11.59 ± 5.97) and 24-hour CCI (6.56 ± 4.10 vs. 5.76 ± 4.05). Mean 1-hour CI and 24-hour CI were not significantly different in both study arms (p = 0.254 and p = 0.242 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2.4 vs. 2.2 days, p = 0.767). No differences could be found in transfusion requirement of red blood cells (p = 0.744) between both study arms. There were also no regarding bleeding, adverse events, and acute transfusion reaction(s). Conclusions This study confirms safety of gamma-irradiated PCs for treatment thrombocytopenia. Hemostatic function, transfusion efficacy, bleeding, and safety of single-donor apheresis PCs treated with gamma irradiation versus untreated control PCs are comparable. PMID:25053932

  3. Anti B cell therapy (rituximab) in the treatment of autoimmune diseases.

    PubMed

    Kazkaz, Hanadi; Isenberg, David

    2004-08-01

    B cells play an important role in the pathogenesis of many autoimmune diseases. Selective targeting of these cells has been recently achieved using a chimeric monoclonal antibody against the pan B cell surface marker CD20 (rituximab). This antibody was originally developed for the treatment of non-Hodgkin's lymphoma. It was found to be effective, well tolerated and had a very good safety profile. Recent studies have demonstrated the efficacy of rituximab in several refractory autoimmune disorders including rheumatoid arthritis, systemic lupus erythematosus, immune thrombocytopenic purpura, chronic cold agglutinin disease, IgM-mediated neuropathies and mixed cryoglobulinemia. PMID:15251135

  4. An Unusual Presentation of Childhood Vasculitis Presenting in Adulthood: A Challenging Diagnosis of Henoch-Schönlein Purpura

    PubMed Central

    Thongprayoon, Charat; Cheungpasitporn, Wisit; Thamcharoen, Natanong; Bruminhent, Jackrapong

    2014-01-01

    Context: Henoch-Schönlein purpura (HSP), a systemic IgA vascultitis, is uncommon in adults, with an incidence rate of 0.1 to 1.2 per million in adults over 20 years old. This vasculitic syndrome can present as an uncommon cause of intestinal obstruction in older patients. We report a case of an older woman with HSP presenting with small bowel obstruction and vasculitic rash. Case Report: We report a 67-year-old woman who presented with small bowel obstruction and skin rash. Skin biopsy revealed leukocytoclastic vasculitis with +IgA granular deposition within the walls of superficial dermal vessels. Kidney biopsy confirmed the diagnosis of HSP with mild mesangial proliferative IgA nephropathy. Her abdominal pain and small bowel obstruction were improved with conservative treatment. She continued to do well with normal kidney function at a 3-month follow-up visit. Conclusion: HSP, a systemic IgA vasculitis, is a predominantly pediatric vasculitis and is uncommon in adults. In adults, the disease process is identical to that in children. However, gastrointestinal manifestation is less common in older patients, and bowel perforation and obstruction are rare. Intestinal obstruction with skin rash and renal involvement should raise suspicions of HSP. PMID:25489569

  5. Adhesion of Neisseria meningitidis to Dermal Vessels Leads to Local Vascular Damage and Purpura in a Humanized Mouse Model

    PubMed Central

    Melican, Keira; Michea Veloso, Paula; Martin, Tiffany; Bruneval, Patrick; Duménil, Guillaume

    2013-01-01

    Septic shock caused by Neisseria meningitidis is typically rapidly evolving and often fatal despite antibiotic therapy. Further understanding of the mechanisms underlying the disease is necessary to reduce fatality rates. Postmortem samples from the characteristic purpuric rashes of the infection show bacterial aggregates in close association with microvessel endothelium but the species specificity of N. meningitidis has previously hindered the development of an in vivo model to study the role of adhesion on disease progression. Here we introduced human dermal microvessels into SCID/Beige mice by xenografting human skin. Bacteria injected intravenously exclusively associated with the human vessel endothelium in the skin graft. Infection was accompanied by a potent inflammatory response with the secretion of human inflammatory cytokines and recruitment of inflammatory cells. Importantly, infection also led to local vascular damage with hemostasis, thrombosis, vascular leakage and finally purpura in the grafted skin, replicating the clinical presentation for the first time in an animal model. The adhesive properties of the type IV pili of N. meningitidis were found to be the main mediator of association with the dermal microvessels in vivo. Bacterial mutants with altered type IV pili function also did not trigger inflammation or lead to vascular damage. This work demonstrates that local type IV pili mediated adhesion of N. meningitidis to the vascular wall, as opposed to circulating bacteria, determines vascular dysfunction in meningococcemia. PMID:23359320

  6. Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

    ClinicalTrials.gov

    2005-06-23

    Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

  7. Tissue Deposits of IgA-Binding Streptococcal M Proteins in IgA Nephropathy and Henoch-Schönlein Purpura

    PubMed Central

    Schmitt, Roland; Carlsson, Fredric; Mörgelin, Matthias; Tati, Ramesh; Lindahl, Gunnar; Karpman, Diana

    2010-01-01

    IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are diseases characterized by IgA deposits in the kidney and/or skin. Both may arise after upper respiratory tract infections, but the pathogenic mechanisms governing these diseases remain unclear. Patients with IgAN (n = 16) and HSP (n = 17) were included in this study aimed at examining whether IgA-binding M proteins of group A streptococci could be involved. As M proteins vary in sequence, the study focused on the IgA-binding-region (IgA-BR) of three different M proteins: M4, M22, and M60. Renal tissue from IgAN and HSP patients and skin from HSP patients were examined for deposits of streptococcal IgA-BR by immunohistochemistry and electron microscopy using specific antibodies, and a skin sample from a HSP patient was examined by mass spectrometry. IgA-BR deposits were detected in 10/16 IgAN kidneys and 7/13 HSP kidneys. Electron microscopy demonstrated deposits of IgA-BRs in the mesangial matrix and glomerular basement membrane, which colocalized with IgA. Skin samples exhibited IgA-BR deposits in 4/5 biopsies, a result confirmed by mass spectrometry in one patient. IgA-BR deposits were not detected in normal kidney and skin samples. Taken together, these results demonstrate IgA-BR from streptococcal M proteins in patient tissues. IgA-BR, would on gaining access to the circulation, encounter circulatory IgA and form a complex with IgA-Fc that could deposit in tissues and contribute to the pathogenesis of IgAN and HSP. PMID:20056836

  8. Similar disturbances in B cell activity and regulatory T cell function in Henoch-Schonlein purpura and systemic lupus erythematosus

    SciTech Connect

    Beale, M.G. (St. Louis Children's Hospital, MO); Nash, G.S.; Bertovich, M.J.; MacDermott, R.P.

    1982-01-01

    The immunoglobulin synthesizing activities of peripheral mononuclear cells (MNC) from five patients with Henoch-Schonlein purpura (HSP) and eight patients with active systemic lupus erythematosus (SLE) were compared. Cumulative amounts of IgM, IgG, and IgA synthesized and secreted by unstimulated and PWM-stimulated patient cells over a 12-day period were determied in a solid-phase radioimmunoassay. In unstimulated control cultures mean rates of IgM, IgG, and IgA synthesis were less than 250 ng/ml. The synthetic activities of patient MNC were markedly increased. In HSP cultures IgA was the major immunoglobulin class produced (2810 x/divide 1.33 ng/ml) followed by IgG (1754 x/divide 1.32 ng/ml) and IgM (404 x/divide 1.16 ng/ml). In SLE cultures IgA and IgG syntheses were equally elevated (4427 x/divide 1.20 and 4438 x/divide 1.49 ng/ml, respectively) whereas IgM synthesis averaged 967 x/divide 1.66 ng/ml. PWM stimulation of pateient MNC caused a sharp decline in the synthesis of all three immunoglobulin classes. After T cell depletion B cell-enriched fractions from HSP and SLE patients maintained high levels of IgA and IgG synthesis that were inhibited by PWM and by normal allogeneic but not autologous T cells. In PWM-stimulted co-cultures, patient T cells nonspecifically suppressed the synthetic activities of autologous and control B cells. in contrast patient B cells achieved normal levels of immunoglobulin synthesis when cultured with control T cells plus PWM. In longitudinal studies patient B and T cell disturbances persisted despite clinical improvement.

  9. Clinico-pathological association of Henoch-Schoenlein purpura nephritis and IgA nephropathy in children

    PubMed Central

    Mao, Song; Xuan, Xiaoyan; Sha, Yugen; Zhao, Sanlong; Zhu, Chunhua; Zhang, Aihua; Huang, Songming

    2015-01-01

    Objective: Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are similar syndromes. We aimed to determine whether the crescent formation/immunocomplex in glomeruli is associated with the differences of the biochemical indexes between HSPN and IgAN. Methods: We investigated the medical records of 137 HSPN cases and 41 IgAN cases from January 2009 to April 2014 in Nanjing Children’s Hospital of Nanjing Medical University. The clinical and pathological data were analyzed and compared between HSPN and IgAN. Results: HSPN patients had markedly higher levels of blood white blood cell (WBC), hemoglobulin (Hb) and platelet (PLT), lower levels of hematuria, blood nitrogen (BUN) and C4 compared with IgAN cases. Crescents formation and C3 deposition in the kidney did not affect these differences. Significantly lower levels of hematuria, blood IgG, IgM and C4 in HSPN compared with IgAN cases were observed among patients with IgG deposition. Markedly higher levels of WBC and Hb, lower levels of hematuria, creatinine (Cr), C4 in HSPN compared with IgAN cases were observed among patients with IgM deposition. No marked differences of the biochemical indexes were noted between HSPN and IgAN cases among patients with C1q deposition. Markedly higher levels of WBC and Hb, lower level of blood C4 in HSPN compared with IgAN cases were observed among patients with fibrogen deposition. Conclusions: The different levels of biochemical indexes at presentation between HSPN and IgAN may be associated with the deposition of IgG, IgM, C1q and fibrogen in the kidney.

  10. Antigen and substrate withdrawal in the management of autoimmune thrombotic disorders

    PubMed Central

    McCrae, Keith R.; Zheng, X. Long; Sachais, Bruce S.; Luning Prak, Eline T.; Siegel, Don L.

    2012-01-01

    Prevailing approaches to manage autoimmune thrombotic disorders, such as heparin-induced thrombocytopenia, antiphospholipid syndrome and thrombotic thrombocytopenic purpura, include immunosuppression and systemic anticoagulation, though neither provides optimal outcome for many patients. A different approach is suggested by the concurrence of autoantibodies and their antigenic targets in the absence of clinical disease, such as platelet factor 4 in heparin-induced thrombocytopenia and ?2-glycoprotein-I (?2GPI) in antiphospholipid syndrome. The presence of autoantibodies in the absence of disease suggests that conformational changes or other alterations in endogenous protein autoantigens are required for recognition by pathogenic autoantibodies. In thrombotic thrombocytopenic purpura, the clinical impact of ADAMTS13 deficiency caused by autoantibodies likely depends on the balance between residual antigen, that is, enzyme activity, and demand imposed by local genesis of ultralarge multimers of von Willebrand factor. A corollary of these concepts is that disrupting platelet factor 4 and ?2GPI conformation (or ultralarge multimer of von Willebrand factor oligomerization or function) might provide a disease-targeted approach to prevent thrombosis without systemic anticoagulation or immunosuppression. Validation of this approach requires a deeper understanding of how seemingly normal host proteins become antigenic or undergo changes that increase antibody avidity, and how they can be altered to retain adaptive functions while shedding epitopes prone to elicit harmful autoimmunity. PMID:22966172

  11. [Detection, diagnosis and analysis of the first case of neonatal alloimmune thrombocytopenia purpura associated with anti-HPA-5b in China].

    PubMed

    Zhou, Yan; Zhong, Zhou-Lin; Li, Li-Lan; Shen, Wei-Dong; Wu, Guo-Guang

    2014-04-01

    This study was aimed to investigate the detection and diagnosis of the neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti-HPA-5b antibody. The platelet count and clinical manifestation in the newborn were examined. The HPA-1-21bw genotypes of the newborn and her parents were detected by multiple-PCR and DNA sequencing. The HPA-specific antibody in the sera of newborn and her mother were detected and identified by flow cytometry (FCM) and monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The results indicated that the clinical manifestations of the newborn were lighter. The HPA genotyping showed that the genotype of the newborn was HPA-5ab, while that of her mother and father were HPA-5aa and HPA-5ab, respectively. The antibody against the platelet of newborn's father existed in the newborn's mother sera. The HPA antibody of the mother was identified as anti-HPA-5b. It is concluded that the newborn with neonatal alloimmune thrombocytopenia purpura was caused by the antibody against HPA-5b. PMID:24763012

  12. Kawasaki disease and Henoch Schonlein purpura: changing trends at a tertiary care hospital in north India (1993-2008).

    PubMed

    Singh, Surjit; Aulakh, Roosy

    2010-04-01

    The objective of the study was to evaluate the epidemiologic trends (1993-2008) in Kawasaki disease (KD) and Henoch Schonlein purpura (HSP) among children as seen in a tertiary care north Indian hospital. A hospital-based retrospective chart analysis of all the patients diagnosed with KD and HSP in our pediatric rheumatology clinic from January 1993 to December 2008 was performed. The diagnosis of KD and HSP was based on the American Heart Association and American College of Rheumatology criteria respectively. The collected data were analyzed for any yearly or seasonal trends in the incidence of the two diseases. KD was diagnosed in 196 patients (135 males, 61 females, ratio 2.21:1), while HSP was diagnosed in 209 patients (155 males, 54 females, ratio 2.87:1). The median age at the time of diagnosis was 5.1 +/- 3.04 years (range 4 months-14 years) for KD and 6.9 +/- 2.98 years (range 1-17 years) for HSP. Over this 16-year period, the number of patients diagnosed with KD progressively increased from 1993 to 2008 (p < 0.001, chi-square test) with a clear majority of these (162 cases, 82.6%) being diagnosed in the last 8 years. The number of children diagnosed with HSP progressively increased from 1993 to 1997, after which it has remained relatively uniform, and only 93 cases (44.5%) were diagnosed in the last 8-year period (p > 0.05, chi-square test). However, both the diseases exhibited a comparable seasonal trend in the distribution with a noticeable peak being discernible in the months of October and November. KD has shown a rising trend over the recent years in our hospital. Since 2004; the annual number of KD cases has outnumbered the HSP cases. Seasonal predilection is noticeable for both conditions. This is the first hospital-based report on epidemiological trends of KD and HSP from a developing country. PMID:19633856

  13. The Interaction between Circulating Complement Proteins and Cutaneous Microvascular Endothelial Cells in the Development of Childhood Henoch-Schönlein Purpura

    PubMed Central

    Yang, Yao-Hsu; Tsai, I-Jung; Chang, Chun-Jung; Chuang, Ya-Hui; Hsu, Hui-Yao; Chiang, Bor-Luen

    2015-01-01

    Objective In addition to IgA, the deposition of complement (C)3 in dermal vessels is commonly found in Henoch-Schönlein purpura (HSP). The aim of this study is to elucidate the role of circulating complement proteins in the pathogenesis of childhood HSP. Methods Plasma levels of C3a, C4a, C5a, and Bb in 30 HSP patients and 30 healthy controls were detected by enzyme-linked immunosorbent assay (ELISA). The expression of C3a receptor (C3aR), C5a receptor (CD88), E-selectin, intercellular adhesion molecule 1 (ICAM-1), C3, C5, interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, and RANTES by human dermal microvascular endothelial cells (HMVEC-d) was evaluated either by flow cytometry or by ELISA. Results At the acute stage, HSP patients had higher plasma levels of C3a (359.5 ± 115.3 vs. 183.3 ± 94.1 ng/ml, p < 0.0001), C5a (181.4 ± 86.1 vs. 33.7 ± 26.3 ng/ml, p < 0.0001), and Bb (3.7 ± 2.6 vs. 1.0 ± 0.6 ?g/ml, p < 0.0001), but not C4a than healthy controls. Although HSP patient-derived acute phase plasma did not alter the presentation of C3aR and CD88 on HMVEC-d, it enhanced the production of endothelial C3 and C5. Moreover, C5a was shown in vitro to up-regulate the expression of IL-8, MCP-1, E-selectin, and ICAM-1 by HMVEC-d with a dose-dependent manner. Conclusion In HSP, the activation of the complement system in part through the alternative pathway may have resulted in increased plasma levels of C3a and C5a, which, especially C5a, may play a role in the disease pathogenesis by activating endothelium of cutaneous small vessels. PMID:25760949

  14. Lack of association between macrophage migration inhibitory factor gene promoter (-173 G/C) polymorphism and childhood Henoch-Schönlein purpura in Turkish patients.

    PubMed

    Nalbantoglu, Sinem; Tabel, Y?lmaz; Mir, Sevgi; Berdeli, Afig

    2013-04-01

    Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis of autoimmune hypersensitivity with rash, arthritis, abdominal pain and renal involvements. Macrophage migration inhibitory factor (MIF) is a immunoregulatory proinflammatory cytokine, and a major mediator at the inflammatory sites. The pathogenesis of HSP has not been fully elucidated. Here we aimed to assess the influence of macrophage migration inhibitory factor gene (-173 G/C) polymorphism in the susceptibility and clinical expression of patients with Henoch-Schönlein purpura (HSP). HSP patients (n:139) and ethnically matched healthy controls (n:100) were genotyped by PCR-RFLP. Genotype analysis of both polymorphisms did not reveal a significant deviation from Hardy-Weinberg equilibrium in any group (p > 0.05). No significant difference was obtained in genotype distribution (p > 0.05) and allele frequencies (p > 0.05) between patients and controls. A statistically significant genotype-phenotype correlation was not obtained when HSP patients were stratified by the presence of certain systemic complications and the macrophage migration inhibitory factor gene (-173 G/C) polymorphism (p > 0.05). A significant risk was not observed in the subjects both with the GC+CC genotype (p = 0.06, OR: 0.5538, 95% CI: 0.2985-1.0274) and C allele (odds ratio: C vs. G: 1.799, 95% CI: 1.002-3.23, p = 0.05). Our findings suggest that MIF gene -173 G/C polymorphism is not associated with HSP in the present Turkish population. PMID:23523092

  15. Targeted ?-Therapy

    PubMed Central

    Brechbiel, Martin W.

    2008-01-01

    Monoclonal antibodies have become a viable strategy for the delivery of therapeutic, particle emitting radionuclides specifically to tumor cells to either augment anti-tumor action of the native antibodies or to solely take advantage of their action as targeting vectors. Proper and rational selection of radionuclide and antibody combinations is critical to making radioimmunotherapy (RIT) a standard therapeutic modality due to the fundamental and significant differences in the emission of either ?- and ?-particles. The ?-particle has a short path length (50-80 ?m) that is characterized by high linear energy transfer (?100 keV/?m). Actively targeted ?-therapy potentially offers a more specific tumor cell killing action with less collateral damage to the surrounding normal tissues than ß-emitters. These properties make targeted ?-therapy appropriate therapies to eliminate of minimal residual or micrometastatic disease. RIT using ?-emitters such as 213Bi, 211At, 225Ac, and others has demonstrated significant activity in both in vitro and in vivo model systems. Limited numbers of clinical trials have progressed to demonstrate safety, feasibility, and therapeutic activity of targeted ?-therapy, despite having to traverse complex obstacles. Further advances may require more potent isotopes, additional sources and more efficient means of isotope production. Refinements in chelation and/or radiolabeling chemistry combined with rational improvements of isotope delivery, targeting vectors, molecular targets, and identification of appropriate clinical applications remains as active areas of research. Ultimately, randomized trials comparing targeted ?-therapy combined with integration into existing standard of care treatment regimens will determine the clinical utility of this modality. PMID:17992276

  16. Henoch-Schönlein Purpura

    MedlinePLUS

    ... org American Society of Pediatric Nephrology 3400 Research Forest Drive, Suite B–7 The Woodlands, TX 77381 Phone: 281–419–0052 Fax: 281–419–0082 Email: info@aspneph.com Internet: www.aspneph.com National Institute of Arthritis and Musculoskeletal and Skin Diseases ...

  17. Progressive Pigmentary Purpura

    MedlinePLUS

    ... the American Osteopathic College of Dermatology. Community Search Search » Sign In Remember Me Forgot your password? Haven't registered yet? more Calendar 10/16/2015 » 10/18/2015 2015 AOCD Fall Meeting 3/30/2016 » 4/3/2016 2016 AOCD Spring Current Concepts in Dermatology Meeting 3/29/2017 » 4/2/ ...

  18. Henoch-Schonlein Purpura

    MedlinePLUS

    ... resolved. HSP is the most common form of vasculitis in children, with an annual incidence on the ... can be mimicked by other forms of systemic vasculitis that are more often life-threatening. Granulomatosis with ...

  19. On Target

    NSDL National Science Digital Library

    WGBH

    2010-01-01

    In this design challenge activity, learners modify a cup so it can carry a marble down a zip line and also drop it onto a target. Learners are encouraged to brainstorm answers to design questions, build a prototype using simple materials, and test, evaluate, and redesign their structure. The activity guide includes troubleshooting tips. The related Leader's Notes guide contains information on how to connect this to NASA and aerospace engineering.

  20. Immune thrombocytopenia after renal transplantation for IgA nephropathy.

    PubMed

    Talaulikar, Dipti; Falk, Michael; Talaulikar, Girish; Pidcock, Michael

    2007-01-01

    Immune thrombocytopenic purpura associated with renal disease is usually therapy-related, occurring after administration of intravenous immunoglobulin therapy or anti-D. Secondary cases occurring after renal transplantation are extremely rare. We present the second reported case of immune thrombocytopenic purpura occurring after renal transplantation for IgA nephropathy. Primary IgA nephropathy is the most common form of primary glomerulonephritis and although the pathogenesis of the disease remains incompletely understood, recent evidence suggests that the basic abnormality lies within the IgA immune system rather than in the kidney. We postulate a novel mechanism for thrombocytopenia occurring in such cases. PMID:17106188

  1. Immune thrombocytopenia. Use of a Coombs antiglobulin test to detect IgG and C3 on platelets

    Microsoft Academic Search

    Douglas B. Cines; Alan D. Schreiber

    1979-01-01

    We applied a radiolabeled Coombs antiglobulin test to the diagnosis and management of immune thrombocytopenia in adults and children. This assay substantiated that the majority of patients with idiopathic thrombocytopenic purpura have increased levels of IgG on their platelets. Platelets from a patient with the post-transfusion-purpura syndrome also carried increased IgG, indicating a role for IgG antibody or IgG-containing immune

  2. [Targeted therapy].

    PubMed

    Niitsu, Nozomi

    2014-03-01

    Rituximab, a genetically engineered chimeric monoclonal antibody that specifically binds to CD20, is the first monoclonal antibody approved for the treatment of B-cell lymphoma. It has been shown that rituximab exerts cytotoxic activities through CDC and ADCC, and that it directly induces apoptosis. The CD20 protein has four transmembrane domains (tetraspan structure) and is not internalized following antibody binding, and is not shed or secreted into the circulation. Therefore, CD20 can serve as a target of antibody therapy. As the other anti-CD20 antibodies, there are ofatumumab and obinutuzumab, and clinical development is expected. In addition, histone deacetylate inhibitor or proteasome inhibitor as a new drugs for lymphoma in the future. PMID:24724406

  3. An analysis of the levels of the soluble form of the endothelial protein C receptor in children with Henoch-Schönlein Purpura.

    PubMed

    Cayci, Fatma Semsa; Ekim, Mesiha; Egin, Yonca; Gökce, Hafize; Yalcinkaya, Fatos; Ozcakar, Birsin; Akar, Nejat

    2015-03-01

    The pathogenesis of Henoch-Schönlein Purpura (HSP) has not been clearly defined. Inflammatory cytokines have been associated with HSP but there are only a few reports that have focused on coagulation. The endothelial protein C receptor (EPCR), which has anticoagulant and antiinflammatory activity, is the key component of the protein C pathway. Recent studies have implicated the soluble form of EPCR (sEPCR) in Wegener's granulomatosis, Behçet's disease, and systemic lupus erythematosus. The aim of this study was to evaluate the levels of sEPCR in HSP children. Twenty-two children with HSP and 17 healthy children were included. We found no significant differences (P > .05) between patient and control groups in the levels of von Willebrand factor and thrombomodulin. The median sEPCR values in the HSP group were lower than the control group (79 vs. 102 ng/mL, respectively) (P > .05). The mean sEPCR value in HSP patients with severe abdominal pain was lower than without (88.8 ± 54.9 vs. 108.2 ± 66.3 ng/mL, respectively) (P > .05). In addition, the mean IL-6 serum levels were significantly elevated in HSP patients during the acute stage of HSP (2.1 ± 1.7 vs. 1.5 ± 1.2 pg/mL, P = .038). We also observed a slight negative correlation between the levels of sEPCR and IL-6 (R = -.135, P > .05). To our knowledge, this was the first study to analyze sEPCR levels in HSP. Our results did not conclusively identify a direct role of sEPCR in HSP, but our findings warrant further investigations, especially in severe HSP cases characterized by gastrointestinal bleeding or renal involvement. PMID:24308805

  4. The level of IgA antibodies to human umbilical vein endothelial cells can be enhanced by TNF-? treatment in children with Henoch–Schönlein purpura

    PubMed Central

    Yang, Y -H; Wang, S J; Chuang, Y -H; Lin, Y -T; Chiang, B -L

    2002-01-01

    Anti-endothelial cell antibodies (AECA) have been found to play an important role in many vascular disorders. In order to determine the presence of AECA in children with Henoch–Schönlein purpura (HSP), and to elucidate the pathogenic and clinical value of their measurement in this disease, AECA were detected by immunofluorescence staining and a human umbilical vein endothelial cell (HUVEC)-based enzyme-linked immunosorbent assay (ELISA) in 20 children with HSP, 10 children with juvenile rheumatoid arthritis (JRA) without vasculitis and 10 normal healthy children. Antibodies against another endothelial cells, human dermal microvascular endothelial cells (HMVEC-d) were also detected by cell-based ELISA. In some experiments, we compared the binding activity of antibodies to HUVEC with and without tumour necrosis factor-? (TNF-?) or interleukin-1 (IL-1) pretreatment. Patients with acute onset of HSP had higher serum levels of IgA antibodies, both against HUVEC and against HMVEC-d, than healthy controls (P = 0·001, P = 0·008, respectively). Forty-five per cent of patients had positive IgA AECA to HUVEC, and 35% had positive IgA AECA to HMVEC-d. The titres of IgA antibodies to HUVEC paralleled the disease activity. After TNF-? treatment, the values of IgA AECA to HUVEC in HSP patients were significantly increased (P = 0·02). For IgG and IgM AECA, there was no difference between HSP patients and controls (P = 0·51, P = 0·91). Ten JRA children without vasculitis had no detectable IgG, IgM or IgA AECA activity. The results of this study showed that children with HSP had IgA AECA, which were enhanced by TNF-? treatment. Although the role of these antibodies is not clear, IgA AECA provide another immunological clue for the understanding of HSP. PMID:12390327

  5. Students' Target

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Context image for PIA03648 Ascraeus Mons

    After examining numerous THEMIS images and using the JMars targeting software, eighth grade students from Charleston Middle School in Charleston, IL, selected the location of -8.37N and 276.66E for capture by the THEMIS visible camera during Mars Odyssey's sixth orbit of Mars on Nov. 22, 2005. The students are investigating relationships between channels, craters, and basins on Mars. The Charleston Middle School students participated in the Mars Student Imaging Project (MSIP) and submitted a proposal to use the THEMIS visible camera.

    Image information: VIS instrument. Latitude 8.8S, Longitude 279.6E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  6. MERIT INSTALLATIONMERIT INSTALLATION TargetTarget

    E-print Network

    McDonald, Kirk

    MERIT INSTALLATIONMERIT INSTALLATION TargetTarget CartCart Target Transporter Common Baseplate #12;MERIT INSTALLATIONMERIT INSTALLATION Total supported weight Solenoid: 5500 kg (12000 lbs)g ( ) Hg") to meet CERN facility constraintsy AB/ATB-EA ML, le 30/03/07 2 #12;MERIT INSTALLATIONMERIT INSTALLATION

  7. Amegakaryocytic thrombocytopenia of 4 years duration: successful treatment with antithymocyte globulin.

    PubMed

    Trimble, M S; Glynn, M F; Brain, M C

    1991-06-01

    Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare cause of thrombocytopenia. Since it is a syndrome of diverse etiologies, the optimal treatment is often uncertain. In a patient with longstanding AATP, a complete remission was obtained with antithymocyte globulin. PMID:2069157

  8. Human megakaryocyte production: cell biology and clinical considerations.

    PubMed

    Gewirtz, A M; Hoffman, R

    1990-02-01

    Advances in the methodologic study of megakaryocytopoiesis are discussed, and their effect on the understanding of the production of platelets is included. This knowledge has led to a better understanding of disorders of megakaryocytopoiesis and platelet production. Specific diseases discussed are congenital megakaryocyte hypoplasia, acquired amegakaryocytic thrombocytopenic purpura, myeloproliferative disorders, reactive thrombocytosis, megakaryoblastic leukemia, and megakaryocyte and marrow fibrosis. PMID:2179214

  9. Inactivation of Escherichia coli O157:H7 by cinnamic aldehyde purified from Cinnamomum cassia shoot

    Microsoft Academic Search

    H.-O. Kim; S.-W. Park; H.-D. Park

    2004-01-01

    Escherichia coli O157:H7 is a pathogen, which causes the hemorrhagic colitis, hemolytic uremic syndrome and thrombotic thrombocytopenic purpura in humans. Control of the bacterial cells in foods is an important factor to reduce outbreaks of the foodborne diseases. In this study, cinnamic aldehyde possessing antimicrobial activity against the bacterial cells was purified from the extract of cinnamon (Cinnamomum cassia Blume)

  10. HUS AND TTP

    PubMed Central

    Trachtman, Howard

    2013-01-01

    SYNOPSIS This review will describe the epidemiology, pathophysiology, presentation, clinical causes, treatment, and long-term prognosis of pediatric patients who present with thrombotic microangiopathy (TMA). The focus will be on hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), the most common phenotypes of TMA. PMID:24237985

  11. Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes

    Microsoft Academic Search

    Leon Bernal-Mizrachi; Wenche Jy; Christian Fierro; Rick Macdonough; Hermes A. Velazques; Joshua Purow; Joaquin J. Jimenez; Lawrence L. Horstman; Alexandre Ferreira; Eduardo de Marchena; Yeon S. Ahn

    2004-01-01

    Background: Endothelial Microparticles (EMP) are small fragments of endothelial cell membrane shed during apoptosis or activation. Our group has previously reported elevations of EMP in patients with coronary artery disease (CAD), thrombotic thrombocytopenic purpura (TTP), pre-eclampsia, multiple sclerosis (MS), and severe hypertension (HTN). In the present study, we evaluate the possible relationship between EMP levels and the angiographic severity and

  12. Target Awareness: Lupus

    MedlinePLUS

    ... Target Awareness: Lupus Jan. 15, 2009 Target Awareness: Lupus Target Awareness: Lupus provides a brief overview of ... Email Print Tags for this Story treatments symptoms Lupus FAQ What is lupus? What are the common ...

  13. Electrically charged targets

    DOEpatents

    Goodman, Ronald K. (Livermore, CA); Hunt, Angus L. (Alamo, CA)

    1984-01-01

    Electrically chargeable laser targets and method for forming such charged targets in order to improve their guidance along a predetermined desired trajectory. This is accomplished by the incorporation of a small amount of an additive to the target material which will increase the electrical conductivity thereof, and thereby enhance the charge placed upon the target material for guidance thereof by electrostatic or magnetic steering mechanisms, without adversely affecting the target when illuminated by laser energy.

  14. Analytical modeling of laser pulse heating of embedded biological targets: An application to cutaneous vascular lesions

    NASA Astrophysics Data System (ADS)

    Mirkov, Mirko; Sherr, Evan A.; Sierra, Rafael A.; Lloyd, Jenifer R.; Tanghetti, Emil

    2006-06-01

    Detailed understanding of the thermal processes in biological targets undergoing laser irradiation continues to be a challenging problem. For example, the contemporary pulsed dye laser (PDL) delivers a complex pulse format which presents specific challenges for theoretical understanding and further development. Numerical methods allow for adequate description of the thermal processes, but are lacking for clarifying the effects of the laser parameters. The purpose of this work is to derive a simplified analytical model that can guide the development of future laser designs. A mathematical model of heating and cooling processes in tissue is developed. Exact analytical solutions of the model are found when applied to specific temporal and spatial profiles of heat sources. Solutions are reduced to simple algebraic expressions. An algorithm is presented for approximating realistic cases of laser heating of skin structures by heat sources of the type found to have exact solutions. The simple algebraic expressions are used to provide insight into realistic laser irradiation cases. The model is compared with experiments on purpura threshold radiant exposure for PDL. These include data from four independent groups over a period of 20 years. Two of the data sets are taken from previously published articles. Two more data sets were collected from two groups of patients that were treated with two PDLs (585 and 595 nm) on normal buttocks skin. Laser pulse durations were varied between 0.5 and 40 ms radiant exposures were varied between 3 and 20 J/cm2. Treatment sites were evaluated 0.5, 1, and 24 hours later to determine purpuric threshold. The analytical model is in excellent agreement with a wide range of experimental data for purpura threshold radiant exposure. The data collected by independent research groups over the last 20 years with PDLs with wavelengths ranged from 577 to 595 nm were described accurately by this model. The simple analytical model provides an accurate description of a wide range of experimental data. The model can be used to guide the development of future laser designs and help refine laser parameters.

  15. TARGETing Childhood Cancer

    Cancer.gov

    Published on Office of Cancer Genomics (https://ocg.cancer.gov) Home > TARGETing Childhood Cancer TARGETing Childhood Cancer [1] June 13, 2012 From AACR Cancer Discovery: NCI's Therapeutically Applicable Research to Generate Effective Treatments Initiative,

  16. TARGETing Childhood Cancer

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > TARGETing Childhood Cancer TARGETing Childhood Cancer [1] June 13, 2012 From AACR Cancer Discovery: NCI's Therapeutically Applicable Research to Generate Effective Treatments Initiative,

  17. Therapeutic gene targeting.

    PubMed

    Yáñez, R J; Porter, A C

    1998-02-01

    Gene targeting is the use of homologous recombination to make defined alterations to the genome. One of the possible outcomes of gene targeting is the accurate correction of genetic defects, and this would make it the ideal method of gene therapy for single gene disorder. While gene targeting has been achieved both in human cell lines and in nontransformed, primary human cells, its low efficiency has been a major limitation to its therapeutic potential. Gene therapy in vivo gene targeting is there for impractical without dramatic improvements in targeting efficiency. Ex vivo approaches might more realistically be considered, but would benefit from progress in the isolation and growth of somatic stem cells and improvements in targeting efficiency. We provide here a brief review of the challenges of gene therapy by gene targeting. This is followed by a critical overview of recent developments in gene targeting techniques, and in our understanding of the underlying processes of homologous and nonhomologous recombination. PMID:9578833

  18. High Power Cryogenic Targets

    SciTech Connect

    Gregory Smith

    2011-08-01

    The development of high power cryogenic targets for use in parity violating electron scattering has been a crucial ingredient in the success of those experiments. As we chase the precision frontier, the demands and requirements for these targets have grown accordingly. We discuss the state of the art, and describe recent developments and strategies in the design of the next generation of these targets.

  19. The Targeting of Advertising

    Microsoft Academic Search

    Ganesh Iyer; David Soberman; J. Miguel Villas-Boas

    2005-01-01

    An important question that firms face in advertising is developing effective media strategy. Major improvements in the quality of consumer information and the growth of targeted media vehicles allow firms to precisely target advertising to consumer segments within a market. This paper examines advertising strategy when competing firms can target advertising to different groups of consumers within a market. With

  20. Using TARGET Data

    Cancer.gov

    The TARGET Initiative produces large-scale genomic data for a selected set of pediatric cancers and provides the research community access to those data. The goal for broadly sharing TARGET data is to facilitate the discovery of therapeutic targets for childhood cancers and catalyze the translation of these discoveries into clinical applications.

  1. Graphite targets at LAMPF

    SciTech Connect

    Brown, R.D.; Grisham, D.L.

    1983-01-01

    Rotating polycrystalline and stationary pyrolytic graphite target designs for the LAMPF experimental area are described. Examples of finite element calculations of temperatures and stresses are presented. Some results of a metallographic investigation of irradiated pyrolytic graphite target plates are included, together with a brief description of high temperature bearings for the rotating targets.

  2. Inflation Forecast Targeting: Implementing and Monitoring Inflation Targets

    Microsoft Academic Search

    Lars E. O. Svensson

    1997-01-01

    Inflation targeting is shown to imply inflation forecast targeting: the central bank's inflation forecast becomes an explicit intermediate target. Inflation forecast targeting simplifies both implementation and monitoring of monetary policy. The weight on output stabilization determines how quickly the inflation forecast is adjusted towards the inflation target. Money growth or exchange rate targeting is generally inferior to inflation targeting and

  3. Bar coded retroreflective target

    SciTech Connect

    Vann, C.S.

    2000-01-25

    This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

  4. Moving target exploitation

    Microsoft Academic Search

    Bruce L. Johnson; Timothy P. Grayson

    1998-01-01

    The understanding of maneuvering forces is invaluable to the warfighter, as it enhances understanding of enemy force structure and disposition, provides cues to potential enemy actions, and expedites targeting of time critical targets. Airborne ground moving target indicator (GMTI) radars are a class of highly-effective, all-weather, wide-area senors that aid in the surveillance of these moving ground vehicles. Unfortunately conventional

  5. Targeting the tumor microenvironment

    SciTech Connect

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

  6. Targeted Radionuclide Therapy

    PubMed Central

    Ersahin, Devrim; Doddamane, Indukala; Cheng, David

    2011-01-01

    Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose. PMID:24213114

  7. GWAS and drug targets

    PubMed Central

    2014-01-01

    Background Genome wide association studies (GWAS) have revealed a large number of links between genome variation and complex disease. Among other benefits, it is expected that these insights will lead to new therapeutic strategies, particularly the identification of new drug targets. In this paper, we evaluate the power of GWAS studies to find drug targets by examining how many existing drug targets have been directly 'rediscovered' by this technique, and the extent to which GWAS results may be leveraged by network information to discover known and new drug targets. Results We find that only a very small fraction of drug targets are directly detected in the relevant GWAS studies. We investigate two possible explanations for this observation. First, we find evidence of negative selection acting on drug target genes as a consequence of strong coupling with the disease phenotype, so reducing the incidence of SNPs linked to the disease. Second, we find that GWAS genes are substantially longer on average than drug targets and than all genes, suggesting there is a length related bias in GWAS results. In spite of the low direct relationship between drug targets and GWAS reported genes, we found these two sets of genes are closely coupled in the human protein network. As a consequence, machine-learning methods are able to recover known drug targets based on network context and the set of GWAS reported genes for the same disease. We show the approach is potentially useful for identifying drug repurposing opportunities. Conclusions Although GWA studies do not directly identify most existing drug targets, there are several reasons to expect that new targets will nevertheless be discovered using these data. Initial results on drug repurposing studies using network analysis are encouraging and suggest directions for future development. PMID:25057111

  8. Knowing Your Learning Target

    ERIC Educational Resources Information Center

    Moss, Connie M.; Brookhart, Susan M.; Long, Beverly A.

    2011-01-01

    No matter what we decide students need to learn, not much will happen until students understand what they are supposed to learn during a lesson and set their sights on learning it. Crafting learning targets for each lesson and deliberately sharing them with students is one way to give students the direction they need. Targets that tell students…

  9. Inflation Targeting: Some Extensions

    Microsoft Academic Search

    Lars E. o. Svensson

    1998-01-01

    Previous analyses of the implementation of inflation targeting are extended to monetary policy responses to different shocks, consequences of model uncertainty, and effects of interest rate smoothing and stabilization. Model uncertainty, output stabilization, and interest rate stabilization or smoothing all call for a more gradual adjustment of the conditional inflation forecast toward the inflation target. The conditional inflation forecast is

  10. Moving target exploitation

    NASA Astrophysics Data System (ADS)

    Johnson, Bruce L.; Grayson, Timothy P.

    1998-08-01

    The understanding of maneuvering forces is invaluable to the warfighter, as it enhances understanding of enemy force structure and disposition, provides cues to potential enemy actions, and expedites targeting of time critical targets. Airborne ground moving target indicator (GMTI) radars are a class of highly-effective, all-weather, wide-area senors that aid in the surveillance of these moving ground vehicles. Unfortunately conventional GMTI radars are incapable of identifying individual vehicles, and techniques for exploiting information imbedded within GMTI radar reports are limited. The Defense Advanced Research Projects Agency (DARPA) Moving Target Exploitation (MTE) program is working to mitigate these deficiencies by developing, integrating, and evaluating a suite of automated and semi-automated technologies to classify moving targets and units, and to provide indications of their activities. These techniques include: aid in the interpretation of GMTI data to provide moving force structure analysis, automatic tracking of thousands of moving ground vehicles, 1-D target classification based upon high-range- resolution (HRR) radar profiles, and 2-D target classification based upon moving target imaging (MTIm) synthetic aperture radar (SAR). This paper shall present the MTE concept and motivation and provide an overview of results to date.

  11. Target Motion Analysis Visualisation

    Microsoft Academic Search

    Andrew Cunningham; Bruce H. Thomas

    2005-01-01

    Target motion analysis (TMA) visualisation is used by naval ships to locate targets around ownship when more accurate methods such as active sonar are not viable. TMA utilises an array of data, the main source being passive sonar, and results in an almost infinite number of possible solutions. These solutions must be filtered by the TMA operator to identify the

  12. Step tracking shrinking targets

    NASA Technical Reports Server (NTRS)

    Johnson, Walter W.; Hart, Sandra G.

    1987-01-01

    Four models describing how people might acquire targets that dynamically vary in size were examined; two that described movement speed as a simple function of target size (either initial or final) and two that described movement speed as a function of the predicted size of the targets at a fixed time in the future (one was referenced to the beginning of the reaction time phase, and the other to the end of this phase). It was found that movement time was best described as a function of a size prediction made at the end, rather than the start, of the reaction time phase. Subjective workload ratings primarily reflected the total amount of time needed to acquire the targets rather than the time pressure imposed by the diminishing size of these targets.

  13. Therapeutic targets for neuroblastomas

    PubMed Central

    Brodeur, Garrett M; lIyer, Radhika; Croucher, Jamie L; Zhuang, Tiangang; Higashi, Mayumi; Kolla, Venkatadri

    2014-01-01

    Introduction Neuroblastoma (NB) is the most common and deadly solid tumor in children. Despite recent improvements, the long-term outlook for high-risk NB is still < 50%. Further, there is considerable short- and long-term toxicity. More effective, less toxic therapy is needed, and the development of targeted therapies offers great promise. Areas covered Relevant literature was reviewed to identify current and future therapeutic targets that are critical to malignant transformation and progression of NB. The potential or actual NB therapeutic targets are classified into four categories: i) genes activated by amplification, mutation, translocation or autocrine overexpression; ii) genes inactivated by deletion, mutation or epigenetic silencing; iii) membrane-associated genes expressed on most NBs but few other tissues; or iv) common target genes relevant to NB as well as other tumors. Expert opinion Therapeutic approaches have been developed to some of these targets, but many remain untargeted at the present time. It is unlikely that single targeted agents will be sufficient for long-term cure, at least for high-risk NBs. The challenge will be how to integrate targeted agents with each other and with conventional therapy to enhance their efficacy, while simultaneously reducing systemic toxicity. PMID:24387342

  14. Solid Target for a Neutrino Factory Neutrino Factory Target Concepts

    E-print Network

    McDonald, Kirk

    of the target material. These shocks can potentially exceed the mechanical strength of solid materialsSolid Target for a Neutrino Factory Neutrino Factory Target Concepts Parameters of the Neutrino Factory Target Proton Beam pulsed 50 Hz bunches 3 (2 ns rms) energy 10 GeV beam power 4 MW Target (not

  15. Tracking Visible Targets Automatically

    NASA Technical Reports Server (NTRS)

    Armstrong, R. W.

    1984-01-01

    Report summarizes techniques for automatic pointing of scientific instruments by reference to visible targets. Applications foreseen in industrial robotics. Measurement done by image analysis based on gradient edge location, image-centroid location and/or outline matching.

  16. Penetration of concrete targets

    Microsoft Academic Search

    M. J. Forrestal; J. D. Cargile; R. D. Y. Tzou

    1993-01-01

    We developed penetration equations for ogive-nosed projectiles that penetrated concrete targets after normal impact. Our penetration equations predict axial force on the projectile nose, rigid-body motion, and final penetration depth. For target constitutive models, we conducted triaxial material experiments to confining pressures of 600 MPa and curve-fit these data with a linear pressure-volumetric strain relation and with a linear Mohr-Coulomb,

  17. Solid Target Options S. Childress

    E-print Network

    McDonald, Kirk

    Solid Target Options NuFACT'00 S. Childress Solid Target Options · The choice of a primary beam to demonstrate basic feasibility #12;Solid Target Options NuFACT'00 S. Childress Case for a Solid Target power is higher than for existing solid target designs - but not by a large factor. · NuMI graphite

  18. High power density targets

    NASA Astrophysics Data System (ADS)

    Pellemoine, Frederique

    2013-12-01

    In the context of new generation rare isotope beam facilities based on high-power heavy-ion accelerators and in-flight separation of the reaction products, the design of the rare isotope production targets is a major challenge. In order to provide high-purity beams for science, high resolution is required in the rare isotope separation. This demands a small beam spot on the production target which, together with the short range of heavy ions in matter, leads to very high power densities inside the target material. This paper gives an overview of the challenges associated with this high power density, discusses radiation damage issues in targets exposed to heavy ion beams, and presents recent developments to meet some of these challenges through different projects: FAIR, RIBF and FRIB which is the most challenging. Extensive use of Finite Element Analysis (FEA) has been made at all facilities to specify critical target parameters and R&D work at FRIB successfully retired two major risks related to high-power density and heavy-ion induced radiation damage.

  19. Increased transforming growth factor-beta (TGF-?)-secreting T cells and IgA anti-cardiolipin antibody levels during acute stage of childhood Henoch–Schönlein purpura

    PubMed Central

    Yang, Y-H; Huang, M-T; Lin, S-C; Lin, Y-T; Tsai, M-J; Chiang, B-L

    2000-01-01

    Henoch–Schönlein purpura (HSP) is a small vessel vasculitis characterized by increased serum IgA and IgA-dominant immune complex deposition in lesions. The involvement of IgA implies a probable role for TGF-?, a major factor in IgA production, in the pathogenesis of HSP. Among IgA antibodies, serum IgA anti-cardiolipin antibodies (aCL) have been found in many diseases, including vasculitis. In addition to the clinical presentations and laboratory parameters, we further investigated the roles of IgA aCL and TGF-? in childhood HSP. Twenty-six Chinese children with the diagnosis of HSP were enrolled. Blood samples from these patients were collected at both acute and convalescent stages. Intracellular staining of lymphocytes was performed to enumerate type 1 (interferon-gamma-secreting), type 2 (IL-4-secreting), and type 3 (TGF-?-secreting) helper T cells. Serum levels of TGF-? were detected by ELISA. Serum IgA aCL of 21 of 26 patients at the acute stage, 11 of them at the convalescent stage, were measured by ELISA. The data showed that IgA aCL serum levels were significantly elevated in patients compared with healthy controls (P < 0·001), and those patients at the convalescent stage (P < 0·001). In addition, TGF-?-secreting T cells were significantly elevated during the acute stage, and decreased at the convalescent stage. Although more studies are needed, the high prevalence of IgA aCL and increased TGF-?-secreting T cells in children with acute HSP revealed some points which should permit a better understanding of the pathogenesis of HSP. PMID:11091287

  20. Penetration of concrete targets

    SciTech Connect

    Forrestal, M.J. [Sandia National Labs., Albuquerque, NM (United States); Cargile, J.D. [Corps of Engineers, Vicksburg, MS (United States). Waterways Experiment Station; Tzou, R.D.Y. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Mechanical Engineering

    1993-08-01

    We developed penetration equations for ogive-nosed projectiles that penetrated concrete targets after normal impact. Our penetration equations predict axial force on the projectile nose, rigid-body motion, and final penetration depth. For target constitutive models, we conducted triaxial material experiments to confining pressures of 600 MPa and curve-fit these data with a linear pressure-volumetric strain relation and with a linear Mohr-Coulomb, shear strength-pressure relation. To verify our penetration equations, we conducted eleven penetration experiments with 0.90 kg, 26.9-mm-diameter, ogive-nosed projectiles into 1.37-m-diameter concrete targets with unconfined compressive strengths between 32-40 MPa. Predictions from our penetration equation are compared with final penetration depth measurements for striking velocities between 280--800 m/s.

  1. Targeted antithrombotic protein micelles.

    PubMed

    Kim, Wookhyun; Haller, Carolyn; Dai, Erbin; Wang, Xiowei; Hagemeyer, Christoph E; Liu, David R; Peter, Karlheinz; Chaikof, Elliot L

    2015-01-26

    Activated platelets provide a promising target for imaging inflammatory and thrombotic events along with site-specific delivery of a variety of therapeutic agents. Multifunctional protein micelles bearing targeting and therapeutic proteins were now obtained by one-pot transpeptidation using an evolved sortase?A. Conjugation to the corona of a single-chain antibody (scFv), which binds to the ligand-induced binding site (LIBS) of activated GPIIb/IIIa receptors, enabled the efficient detection of thrombi. The inhibition of thrombus formation was subsequently accomplished by incorporating the catalytically active domain of thrombomodulin (TM) onto the micelle corona for the local generation of activated protein?C, which inhibits the formation of thrombin. An effective strategy has been developed for the preparation of protein micelles that can be targeted to sites of activated platelets with broad potential for treatment of acute thrombotic events. PMID:25504546

  2. Obsession with targets.

    PubMed

    Anil, P

    1994-06-01

    Every year from January to March throughout India the entire Family Welfare Department is active to achieve targets for family planning. Experts on population have determined that India needs to achieve a couple protection rate (CPR) of 60% by the year 2000 to reduce the population growth rate and help stabilize the population. CPR is defined as the percentage of eligible couples effectively protected against childbirth by one or the other approved methods of family planning: sterilization, IUD, condom or oral contraceptive (OC) pills. It is estimated that there are 150-180 currently married eligible couples per 1000 population in India where the wife is in the reproductive age. Each state allocates targets: the number of sterilizations to be performed, IUDs to be inserted, and OC pills and condoms to be distributed for each district. The District Medical Officers are allocated targets who direct their subordinates to meet the requirements. The high rate of sterilizations performed as well as coercion and threats are part of target completion. At sterilization camps "motivated acceptors" are sterilized and left alone to bear the side effects. It is estimated that 72 condoms are required by a couple a year. Whether the couple uses the condoms at all is no concern for the target hunters. There have been newspaper reports of large quantities of OC pills and condoms being dumped into ditches. Targets of CPR have been reached with no significant effect on birth rate and growth rate. Deficiencies also exist in relation to the crude birth rate and annual population growth rate. 41.2% of the sterilization acceptors have four or more living children. Their inclusion in the records only boosts the CPR statistics with hardly any impact on the demographic scenario. More attention should be paid to quality rather than quantity and holistic health care especially for women and children. PMID:12345779

  3. Target Heart Rate

    NSDL National Science Digital Library

    Mr. Peterson

    2011-09-18

    Students will practice how to calculate their Target Heart Rate to use during exercise routines. This will help students monitor the intensity of their workouts, and ultimately help them achieve results from their workout. Standard 2: Objective 2: a,b,c Before we discuss what the Target Heart Range is and how we can us it, we must first have some basic knowledge of the heart and it's functions. Click the "habits of the heart" to learn the basics of the heart and how it circulates blood throughout the body. Habits of the Heart The hearts ...

  4. Development of an underwater target classifier using target specific features

    Microsoft Academic Search

    M. H. Supriya; P. R. Saseendran Pillai

    2003-01-01

    In Sonar, the detection and estimation functions are performed by signal processors, which involve the computation of various statistics, for enhancing the overall performance of the system. This also takes into account all the undesirable propagation effects caused by the underwater channel. Underwater targets can be classified by using certain target specific features such as target strength, target dynamics, and

  5. Targets of curcumin

    PubMed Central

    Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

    2010-01-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-?B), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

  6. Nanocrystal targeting in vivo

    Microsoft Academic Search

    Maria E. Åkerman; Warren C. W. Chan; Pirjo Laakkonen; Sangeeta N. Bhatia; Erkki Ruoslahti

    2002-01-01

    Inorganic nanostructures that interface with biological systems have recently attracted widespread interest in biology and medicine. Nanoparticles are thought to have potential as novel intravascular probes for both diagnostic (e.g., imaging) and therapeutic purposes (e.g., drug delivery). Critical issues for successful nanoparticle delivery include the ability to target specific tissues and cell types and escape from the biological particulate filter

  7. Targeting Chromatin Readers

    PubMed Central

    James, LI; Frye, SV

    2015-01-01

    Modulation of gene expression through epigenetic signaling has recently emerged as a novel approach in treating human disease. Specifically, chromatin reader proteins, which mediate protein–protein interactions via binding to modified lysine residues, are gaining traction as potential therapeutic targets. Herein, we review recent efforts to understand and modulate the activity of chromatin reader proteins with small-molecule ligands. PMID:23403847

  8. Targeted radionuclide therapy.

    PubMed

    Williams, Lawrence E; DeNardo, Gerald L; Meredith, Ruby F

    2008-07-01

    Targeted radionuclide therapy (TRT) seeks molecular and functional targets within patient tumor sites. A number of agents have been constructed and labeled with beta, alpha, and Auger emitters. Radionuclide carriers spanning a broad range of sizes; e.g., antibodies, liposomes, and constructs such as nanoparticles have been used in these studies. Uptake, in percent-injected dose per gram of malignant tissue, is used to evaluate the specificity of the targeting vehicle. Lymphoma (B-cell) has been the primary clinical application. Extension to solid tumors will require raising the macroscopic absorbed dose by several-fold over values found in present technology. Methods that may effect such changes include multistep targeting, simultaneous chemotherapy, and external sequestration of the agent. Toxicity has primarily involved red marrow so that marrow replacement can also be used to enhance future TRT treatments. Correlation of toxicities and treatment efficiency has been limited by relatively poor absorbed dose estimates partly because of using standard (phantom) organ sizes. These associations will be improved in the future by obtaining patient-specific organ size and activity data with hybrid SPECT/CT and PET/CT scanners. PMID:18697529

  9. Opportunity Spies Its Target

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This is a forward-looking view of the Meridiani Planum plains that lie between the Mars Exploration Rover Opportunity and its primary drive target, 'Endurance Crater.' The images in this image mosaic were taken by the rover's panoramic camera on sol 88.

  10. Target fragmentation in radiobiology

    NASA Technical Reports Server (NTRS)

    Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.; Townsend, Lawrence W.

    1993-01-01

    Nuclear reactions in biological systems produce low-energy fragments of the target nuclei seen as local high events of linear energy transfer (LET). A nuclear-reaction formalism is used to evaluate the nuclear-induced fields within biosystems and their effects within several biological models. On the basis of direct ionization interaction, one anticipates high-energy protons to have a quality factor and relative biological effectiveness (RBE) of unity. Target fragmentation contributions raise the effective quality factor of 10 GeV protons to 3.3 in reasonable agreement with RBE values for induced micronuclei in bean sprouts. Application of the Katz model indicates that the relative increase in RBE with decreasing exposure observed in cell survival experiments with 160 MeV protons is related solely to target fragmentation events. Target fragment contributions to lens opacity given an RBE of 1.4 for 2 GeV protons in agreement with the work of Lett and Cox. Predictions are made for the effective RBE for Harderian gland tumors induced by high-energy protons. An exposure model for lifetime cancer risk is derived from NCRP 98 risk tables, and protraction effects are examined for proton and helium ion exposures. The implications of dose rate enhancement effects on space radiation protection are considered.

  11. Metastatic cancer-related thrombotic microangiopathies: a cohort study.

    PubMed

    Ducos, Guillaume; Mariotte, Eric; Galicier, Lionel; Canet, Emmanuel; Boutboul, David; Lemiale, Virginie; Schlemmer, Benoit; Veyradier, Agnes; Azoulay, Elie; Zafrani, Lara

    2014-08-01

    Thrombotic microangiopathies (TMAs) in patients with metastatic cancer are poorly characterized. We recorded 17 patients who had TMAs associated with disseminated solid cancer in our intensive care unit over an 11-year period. We compared them with a group of 20 patients with proven idiopathic thrombotic thrombocytopenic purpura hospitalized during the same period. We aimed to specify the clinical and biological features of cancer-related TMAs (CR-TMAs). CR-TMAs can either be inaugural of the underlying cancer or reflect worsening course. Clues to the presence of CR-TMA include respiratory symptoms, bone pain, myelemia or higher platelet count than in thrombotic thrombocytopenic purpura. In this context, bone marrow aspiration is a fast and gainful investigation to avoid plasmatherapy and immunosuppressive drugs. Indeed, this severe and poor-prognosis disease requires prompt diagnosis and rapid initiation of specific chemotherapy. PMID:25303053

  12. Targeting nanoparticles to cancer.

    PubMed

    Wang, M; Thanou, M

    2010-08-01

    Nanotechnology applications in medicine, termed as nanomedicine, have introduced a number of nanoparticles of variable chemistry and architecture for cancer imaging and treatment. Nanotechnology involves engineering multifunctional devices with dimensions at the nanoscale, similar dimensions as those of large biological vesicles or molecules in our body. These devices typically have features just tens to hundred nanometers across and they can carry one or two detection signals and/or therapeutic cargo(s). One unique class of nanoparticles is designed to do both, providing this way the theragnostic nanoparticles (therapy and diagnosis). Being inspired by physiologically existing nanomachines, nanoparticles are designed to safely reach their target and specifically release their cargo at the site of the disease, this way increasing the drug's tissue bioavailability. Nanoparticles have the advantage of targeting cancer by simply being accumulated and entrapped in tumours (passive targeting). The phenomenon is called the enhanced permeation and retention effect, caused by leaky angiogenetic vessels and poor lymphatic drainage and has been used to explain why macromolecules and nanoparticles are found at higher ratios in tumours compared to normal tissues. Although accumulation in tumours is observed cell uptake and intracellular drug release have been questioned. Polyethyleneglycol (PEG) is used to protect the nanoparticles from the Reticulo-Endothelial System (RES), however, it prevents cell uptake and the required intracellular drug release. Grafting biorecognition molecules (ligands) onto the nanoparticles refers to active targeting and aims to increase specific cell uptake. Nanoparticles bearing these ligands are recognised by cell surface receptors and this leads to receptor-mediated endocytosis. Several materials are suggested for the design of nanoparticles for cancer. Polymers, linear and dendrimers, are associated with the drug in a covalent or non-covalent way and have been used with or without a targeting ligand. Stealth liposomes are suggested to carry the drug in the aqueous core, and they are usually decorated by recognition molecules, being widely studied and applied. Inorganic nanoparticles such as gold and iron oxide are usually coupled to the drug, PEG and the targeting ligand. It appears that the PEG coating and ligand decoration are common constituents in most types of nanoparticles for cancer. There are several examples of successful cancer diagnostic and therapeutic nanoparticles and many of them have rapidly moved to clinical trials. Nevertheless there is still a room for optimisation in the area of the nanoparticle kinetics such as improving their plasma circulation and tumour bioavailability and understanding the effect of targeting ligands on their efficiency to treat cancer. The need to develop novel and efficient ligands has never been greater, and the use of proper conjugation chemistry is mandatory. PMID:20380880

  13. Air target algorithm development (ATAD)

    Microsoft Academic Search

    B. Overfield; J. Thomas; M. Cohen; V. Sylvester; R. Rogers; D. Morgan

    1998-01-01

    The Combat Air Forces have invested heavily in a sensor and weapon capability to detect and attack air targets at long ranges. Unfortunately, the ability to identify these targets lags behind these capabilities. Under the Air Force sponsored Air Target Algorithm Development (ATAD) program, model-based reasoning (MBR) fusion algorithms have been developed and demonstrated for improved air target identification (ID).

  14. Affordable moving surface target engagement

    Microsoft Academic Search

    M. Veth; J. Busque; D. Heesch; T. Burgess; F. Douglas; B. Kish

    2002-01-01

    This paper presents the results of the Defense Advanced Research Project Agency-funded Affordable Moving Surface Target Engagement program. The overall objective was to develop affordable technologies to engage moving surface targets such as tanks, tactical ballistic missile transporters and small boats. The Northrop Grumman team used moving target indicator sensors on multiple aircraft to individually track moving ground targets. Report

  15. Laboratory evaluation of a bleeding patient.

    PubMed Central

    Wallerstein, R O

    1989-01-01

    Most causes of abnormal bleeding can be determined from a complete blood count including platelet count and bleeding, prothrombin, activated partial thromboplastin, and thrombin times. Occasionally, further evaluation is necessary, such as tests of factor XIII function, fibrinolysis, and vascular integrity. Possible diagnoses include disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, vitamin K deficiency, von Willebrand's disease, heparin-induced thrombocytopenia, acquired inhibitors of factor VIII, lupus anticoagulants, and coagulation disorders related to the acquired immunodeficiency syndrome. PMID:2660407

  16. Severe Thrombocytopenia in Aged Rhesus Macaques (Macaca mulatta) Infected with Simian Varicella Virus

    PubMed Central

    Halliday, Lisa C; Fortman, Jeffrey D

    2011-01-01

    Simian varicella virus was diagnosed in 2 geriatric rhesus macaques (Macaca mulatta). The macaques presented with typical skin lesions as well as severe thrombocytopenia as a result of infection. Idiopathic thrombocytopenic purpura is a known complication of varicella zoster virus infection in humans; however, this condition has not been reported previously as a complication of SVV infection. This case report discusses the clinical presentation, pathology, and thrombocytopenia of the affected macaques. PMID:21333173

  17. 47,XXX in an Adolescent with Premature Ovarian Failure and Autoimmune Disease

    Microsoft Academic Search

    C. M Holland

    2001-01-01

    Background: Premature ovarian failure (POF) may be idiopathic or may be associated with genetic or autoimmune disorders. The 47,XXX karyotype has been associated with POF and other genitourinary anomalies.Case: A 17-year-old woman with a history of immune thrombocytopenic purpura was referred to the adolescent medicine clinic for evaluation of oligomenorrhea with secondary amenorrhea. Evaluation revealed hypergonadotrophic premature ovarian failure, a

  18. Inhibition of Autoantibody Binding to Platelet Glycoprotein lib\\/Illa by Anti-Idiotypic Antibodies in Intravenous Gammaglobulin

    Microsoft Academic Search

    Peter Berchtold; George L. Dale; Patricia Tani; Robert McMillan

    1989-01-01

    Intravenous immunoglobulin (lVlgG) causes an acute rise in the platelet count in the majority of patients with chronic immune thrombocytopenic purpura (ITP) but the mecha- nism(s) of action is still unknown. We evaluated the ability of three different IVIgG preparations to inhibit the in vitro binding of autoantibody to platelet glycoprotein (GP) llb\\/ lila. ITP plasma. known to contain anti-GPIIb\\/Illa

  19. Autoantibodies Against the Platelet Glycoprotein lib\\/Illa Complex in Patients With Chronic ITP

    Microsoft Academic Search

    Virgil L. Woods; Esther H. Oh; Donna Mason; Robert McMillan

    1984-01-01

    Chronic idiopathic thrombocytopenic purpura (ITP) is caused by an antibody reactive with platelet-associated antigens. The present studies provide direct evidence that some patients with chronic ITP have autoantibodies against the platelet glycoprotein (GP) lIb\\/Illa complex. Microtiter wells. coated with a monoclonal antibody (2G12) specific for GPIIb\\/GPIlIa were reacted with GPlIb\\/GPlIla contained in a platelet extract. Control wells containing the same

  20. Molecular targets in glioblastoma.

    PubMed

    Zorzan, Maira; Giordan, Enrico; Redaelli, Marco; Caretta, Antonio; Mucignat-Caretta, Carla

    2015-05-01

    ABSTRACT? Glioblastoma is the most lethal brain tumor. The poor prognosis results from lack of defined tumor margins, critical location of the tumor mass and presence of chemo- and radio-resistant tumor stem cells. The current treatment for glioblastoma consists of neurosurgery, followed by radiotherapy and temozolomide chemotherapy. A better understanding of the role of molecular and genetic heterogeneity in glioblastoma pathogenesis allowed the design of novel targeted therapies. New targets include different key-role signaling molecules and specifically altered pathways. The new approaches include interference through small molecules or monoclonal antibodies and RNA-based strategies mediated by siRNA, antisense oligonucleotides and ribozymes. Most of these treatments are still being tested yet they stay as solid promises for a clinically relevant success. PMID:25952786

  1. Predicting European Takeover Targets

    Microsoft Academic Search

    Gurvinder Brar; Daniel Giamouridis; Manolis Liodakis

    2009-01-01

    AbstractThis article extends the Palepu (1986) acquisition likelihood model by incorporating measures of a technical nature, e.g. momentum, trading volume as well as a measure of market sentiment. We use the proposed model to predict takeover targets in a large sample of European and cross-border merger and acquisition deals and validate its performance on an in- and out-of-sample basis. The

  2. Windowless solid hydrogen target

    Microsoft Academic Search

    S. Ishimoto; T. Kobayashi; K. Morimoto; I. Nomura; A. Ozawa; S. Suzuki; Y. Takahashi; I. Tanihata; T. Tsuru

    2002-01-01

    A windowless solid hydrogen target has been successfully developed for RI-beam-induced nuclear reactions in the RIKEN RI Beam Facility. Hydrogen crystals of high quality were grown reproducibly in a cell bored in a 10mm thick pure copper plate which was in direct contact with a liquid helium reservoir. Normal hydrogen gas was crystallized directly on the cell wall between 4.7

  3. Drug targets in Leishmania

    Microsoft Academic Search

    Bhavna Chawla; Rentala Madhubala

    2010-01-01

    Leishmaniasis is a major public health problem and till date there are no effective vaccines available. The control strategy\\u000a relies solely on chemotherapy of the infected people. However, the present repertoire of drugs is limited and increasing resistance\\u000a towards them has posed a major concern. The first step in drug discovery is to identify a suitable drug target. The genome

  4. Novel diuretic targets

    PubMed Central

    Pao, Alan C.; Maduke, Merritt

    2013-01-01

    As the molecular revolution continues to inform a deeper understanding of disease mechanisms and pathways, there exist unprecedented opportunities for translating discoveries at the bench into novel therapies for improving human health. Despite the availability of several different classes of antihypertensive medications, only about half of the 67 million Americans with hypertension manage their blood pressure appropriately. A broader selection of structurally diverse antihypertensive drugs acting through different mechanisms would provide clinicians with greater flexibility in developing effective treatment regimens for an increasingly diverse and aging patient population. An emerging body of physiological, genetic, and pharmacological evidence has implicated several renal ion-transport proteins, or regulators thereof, as novel, yet clinically unexploited, diuretic targets. These include the renal outer medullary potassium channel, ROMK (Kir1.1), Kir4.1/5.1 potassium channels, ClC-Ka/b chloride channels, UTA/B urea transporters, the chloride/bicarbonate exchanger pendrin, and the STE20/SPS1-related proline/alanine-rich kinase (SPAK). The molecular pharmacology of these putative targets is poorly developed or lacking altogether; however, recent efforts by a few academic and pharmaceutical laboratories have begun to lessen this critical barrier. Here, we review the evidence in support of the aforementioned proteins as novel diuretic targets and highlight examples where progress toward developing small-molecule pharmacology has been made. PMID:23863472

  5. Apparatus for forming targets

    DOEpatents

    Woerner, Robert L. (Livermore, CA)

    1980-01-01

    Apparatus and method for cryoinduced uniform deposition of cryogenic materials, such as deuterium-tritium (DT) mixtures, on the inner surface of hollow spherical members, such as inertially imploded targets. By vaporizing and quickly refreezing cryogenic materials contained within a hollow spherical member, a uniform layer of the materials is formed on the inner surface of the spherical member. Heating of the cryogenic material, located within a non-isothermal compact freezing cell, is accomplished by an electrical heat pulse, whereafter the material is quickly frozen forming a uniform layer on the inner surface of the spherical member. The method is not restricted to producing a frozen layer on only the inner surface of the innermost hollow member, but where multiple concentric hollow spheres are involved, such as in multiple shell targets for lasers, electron beams, etc., layers of cryogenic material may also be formed on the inner surface of intermediate or outer spherical members, thus providing the capability of forming targets having multiple concentric layers or shells of frozen DT.

  6. Targeted Endoscopic Imaging

    PubMed Central

    Li, Meng; Wang, Thomas D

    2011-01-01

    Summary Endoscopy has undergone explosive technological growth in over recent years, and with the emergence of targeted imaging, its truly transformative power and impact in medicine lies just over the horizon. Today, our ability to see inside the digestive tract with medical endoscopy is headed toward exciting crossroads. The existing paradigm of making diagnostic decisions based on observing structural changes and identifying anatomical landmarks may soon be replaced by visualizing functional properties and imaging molecular expression. In this novel approach, the presence of intracellular and cell surface targets unique to disease are identified and used to predict the likelihood of mucosal transformation and response to therapy. This strategy can result in the development of new methods for early cancer detection, personalized therapy, and chemoprevention. This targeted approach will require further development of molecular probes and endoscopic instruments, and will need support from the FDA for streamlined regulatory oversight. Overall, this molecular imaging modality promises to significantly broaden the capabilities of the gastroenterologist by providing a new approach to visualize the mucosa of the digestive tract in a manner that has never been seen before. PMID:19423025

  7. Targeting Systems Characterization Facility

    NASA Astrophysics Data System (ADS)

    Lucius, Charles E.; Waggoner, Drexel G.

    1986-08-01

    For nearly five years, the Air Force Avionics Laboratory has operated the Targeting Systems Characterization Facility (TSCF) at Wright-Patterson Air Force Base, Ohio. This has resulted in an extremely large amount of archived data describing the performance of an infrared sensor, the target and backgrounds observed by the sensor, and the environmental conditions occurring during the measurement periods. Since these data are stored in a digital computer in a rigid format, they can be efficiently and conveniently accessed. The TSCF data are available to the sensor community and have proven to be a valuable asset in the development and validation of the Research Grade Infrared Tactical Decision Aid, and in the investigation of environmental influences on infrared sensor performance. This paper describes the Targeting Systems Characterization Facility itself and demonstrates the usefulness of the data. Emphasis is placed on the measurement procedures and instrumentation used for the data collection. The preparation of this paper is sponsored by the Air Force Avionics Laboratory.

  8. Follicular penetration and targeting.

    PubMed

    Lademann, Jürgen; Otberg, Nina; Jacobi, Ute; Hoffman, Robert M; Blume-Peytavi, Ulrike

    2005-12-01

    In the past, intercellular penetration was assumed to be the most important penetration pathway of topically applied substances. First hints that follicular penetration needs to be taken into consideration were confirmed by recent investigations, presented during the workshop "Follicular Penetration and Targeting" at the 4th Intercontinental Meeting of Hair Research Societies", in Berlin 2004. Hair follicles represent an efficient reservoir for the penetration of topically applied substances with subsequent targeting of distinct cell populations, e.g., nestin-expressing follicular bulge cells. The volume of this reservoir can be determined by differential stripping technology. The follicular penetration processes are significantly influenced by the state of the follicular infundibulum; recent experimental investigations could demonstrate that it is essential to distinguish between open and closed hair follicles. Topically applied substances can only penetrate into open hair follicle. Knowledge of follicular penetration is of high clinical relevance for functional targeting of distinct follicular regions. Human hair follicles show a hair-cycle-dependent variation of the dense neuronal and vascular network. Moreover, during hair follicle cycling with initiation of anagen, newly formed vessels occur. Thus, the potential of nestin-expressing hair follicle stem cells to form neurons and blood vessels was investigated. PMID:16382687

  9. A Note on Inflation Targeting.

    ERIC Educational Resources Information Center

    Lai, Ching-chong; Chang, Juin-jen

    2001-01-01

    Presents a pedagogical graphical exposition to illustrate the stabilizing effect of price target zones. Finds that authorities' commitment to defend a price target zone affects the public's inflation expectations and, in turn, reduces actual inflation. (RLH)

  10. Target mass corrections revisited

    SciTech Connect

    Steffens, F.M. [NFC-FCBEE-Universidade Presbiteriana Mackenzie, Rua da Consolacao 930, 01302-907, Sao Paulo, SP, Brazil IFT-UNESP, Rua Pamplona 145, 01405-900, Sao Paulo, SP (Brazil); Melnitchouk, W. [Jefferson Lab, 12000 Jefferson Avenue, Newport News, Virginia 23606 (United States)

    2006-05-15

    We propose a new implementation of target mass corrections to nucleon structure functions which, unlike existing treatments, has the correct kinematic threshold behavior at finite Q{sup 2} in the x{yields}1 limit. We illustrate the differences between the new approach and existing prescriptions by considering specific examples for the F{sub 2} and F{sub L} structure functions, and discuss the broader implications of our results, which call into question the notion of universal parton distribution at finite Q{sup 2}.

  11. Target Mass Corrections Revisited

    SciTech Connect

    W. Melnitchouk; F. Steffens

    2006-03-07

    We propose a new implementation of target mass corrections to nucleon structure functions which, unlike existing treatments, has the correct kinematic threshold behavior at finite Q{sup 2} in the x {yields} 1 limit. We illustrate the differences between the new approach and existing prescriptions by considering specific examples for the F{sub 2} and F{sub L} structure functions, and discuss the broader implications of our results, which call into question the notion of universal parton distribution at finite Q{sup 2}.

  12. Cryogenic Tritium Target

    SciTech Connect

    Yukhimchuk, A.A. [Russian Federal Nuclear Center-All-Russian Scientific Research Institute of Experimental Physics (Russian Federation); Tumkin, D.P. [Russian Federal Nuclear Center-All-Russian Scientific Research Institute of Experimental Physics (Russian Federation); Boitsov, I.Ye. [Russian Federal Nuclear Center-All-Russian Scientific Research Institute of Experimental Physics (Russian Federation)] (and others)

    2005-07-15

    To measure muon catalyzed fusion (MC) parameters in liquid tritium with the accuracy better than 10% in the reaction tt{mu} {yields} {sup 4}He + n +n+ {mu}, a cryogenic tritium target (CTT) of a 8.1 cm{sup 3} volume was created. The CTT is a radiation-safe complex containing chemically bound tritium in the form of uranium tritide in a special source.In 2003, using the CTT, two runs of measurements with liquid tritium MC parameters were made on the synchrocyclotron muon channel in the Dzhelepov Laboratory of Nuclear Problems, Joint Institute for Nuclear Research (DLNP JINR)

  13. SNS Target Systems Operational

    E-print Network

    McDonald, Kirk

    .0 30.0 45.0 60.0 75.0 90.0 105.0 120.0 135.0 150.0 165.0 180.0 195.0 210.0 225.0 240.0 255.0 270.0 285 production during the next run cycle · The Inconel 718 Proton Beam Window (PBW) was also replaced during 200 300 400 500 600 700 800 Beam power on target [kW] Operatinghours Hour

  14. Open-Economy Inflation Targeting

    Microsoft Academic Search

    Lars E. O. Svensson

    1998-01-01

    The paper examines inflation targeting in a small open economy with forward-looking aggregate supply and demand with microfoundations, and with stylised realistic lags in the different monetary-policy transmission channels. The paper compares strict and flexible targeting of CPI and domestic inflation and inflation-targeting reaction functions and the Taylor rule. Flexible CPI-inflation targeting does not only limit the variability of CPI

  15. Open-economy inflation targeting

    Microsoft Academic Search

    Lars E. O. Svensson

    2000-01-01

    The paper examines inflation targeting in a small open economy with forward-looking aggregate supply and demand with microfoundations, and with stylized realistic lags in the different monetary-policy transmission channels. The paper compares strict and flexible targeting of CPI and domestic inflation, and inflation-targeting reaction functions and the Taylor rule. Flexible CPI-inflation targeting does not limit the variability of CPI inflation

  16. Policy Rules for Inflation Targeting

    Microsoft Academic Search

    Glenn D. Rudebusch; Lars E. O. Svensson

    1998-01-01

    Policy rules that are consistent with inflation targeting are examined in a small macroeconomic model of the US economy. We compare the properties and outcomes of explicit instrument rules' as well as targeting rules.' The latter, which imply implicit instrument rules, may be closer to actual operating procedures of inflation-targeting central banks. We find that inflation forecasts are central for

  17. Oxide Fiber Targets at ISOLDE

    Microsoft Academic Search

    U Köster; U C Bergmann; D Carminati; R Catherall; J Cederkäll; J G Correia; B Crepieux; M Dietrich; K Elder; V Fedosseev; L M Fraile-Prieto; S Franchoo; H O U Fynbo; U Georg; T Giles; A Joinet; O C Jonsson; R Kirchner; C Lau; Jacques Lettry; H J Maier; V I Mishin; M Oinonen; K Peräjärvi; H L Ravn; T Rinaldi; M Santana-Leitner; U Wahl; L Weissman

    2002-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxyde fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some contact points. The experience with various oxyde fiber targets (titania, zirconia, ceria and thoria) used

  18. Oxide fiber targets at ISOLDE

    Microsoft Academic Search

    U. Köster; U. C. Bergmann; D. Carminati; R. Catherall; J. Cederkäll; B. Crepieux; M. Dietrich; K. Elder; V. N. Fedoseyev; L. Fraile; S. Franchoo; H. Fynbo; U. Georg; T. Giles; A. Joinet; O. C. Jonsson; R. Kirchner; Ch. Lau; J. Lettry; H. J. Maier; V. I. Mishin; M. Oinonen; K. Peräjärvi; H. L. Ravn; T. Rinaldi; M. Santana-Leitner; U. Wahl; L. Weissman

    2003-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxide fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some contact points.The experience with various oxide fiber targets (titania, zirconia, ceria and thoria) used in

  19. Rotating Target Development for SNS Second Target Station

    SciTech Connect

    McManamy, Thomas J [ORNL; Rennich, Mark J [ORNL; Crawford, Roy K [ORNL; Geoghegan, Patrick J [ORNL; Janney, Jim G [ORNL

    2010-01-01

    A rotating target for the second target station (STS) at SNS has been identified as an option along with a mercury target. Evaluation of the rotating target alternative for STS has started at 1.5 MW which is considered an upper bound for the power. Previous preconceptual design work for a 3 MW rotating target is being modified for the lower power level. Transient thermal analysis for a total loss of active water cooling has been done for a simplified 2D model of the target and shielding monolith which shows that peak temperatures are well below the level at which tungsten vaporization by steam could exceed site boundary dose limits. Design analysis and integration configuration studies have been done for the target-moderator-reflector assembly which maximizes the number of neutron beam lines and provides for replacement of the target and moderators. Target building hot cell arrangement for this option will be described. An option for operation in rough vacuum without a proton beam window using Ferro fluid seals on a vertical shaft is being developed. A full scale prototypic drive module based on the 3 MW preconceptual design has been fabricated and successfully tested with a shaft and mock up target supplied by the ESS-Bilbao team. Overall planning leading to decision between mercury and the rotating target in 2011 will be discussed

  20. Split-target neutronics and the MLNSC spallation target system

    SciTech Connect

    Russell, G.J.; Ferguson, P.D.; Pitcher, E.J.; Court, J.D.

    1996-12-31

    The Manuel Lujan, Jr., Neutron Scattering Center (MLNSC) at the Los Alamos National Laboratory is one of four operating Short-Pulse Spallation Sources worldwide. The MLNSC target system (composed of targets, moderators, and reflectors) was first installed in 1985. The target system employs a split tungsten spallation target with a void space in between (the flux-trap gap); this target system will be upgraded in 1998. The ability to efficiently split a spallation target allowed us to introduce the concept of flux-trap moderators and ultimately the notion of backscattering and upstream moderators. The upgraded MLNSC target system will employ both flux-trap and upstream/backscattering moderators to simultaneously service 16 neutron flight paths with high-intensity neutron beams for materials science research.

  1. Liquid Hydrogen: Target, Detector

    SciTech Connect

    Mulholland, G.T. [Applied Cryogenics Technology, Ovilla TX 75154 (United States); Harigel, G.G. [CERN, European Organization for Nuclear Research, 1211 Geneva 23 (Switzerland)

    2004-06-23

    In 1952 D. Glaser demonstrated that a radioactive source's radiation could boil 135 deg. C superheated-diethyl ether in a 3-mm O glass vessel and recorded bubble track growth on high-speed film in a 2-cm3 chamber. This Bubble Chamber (BC) promised improved particle track time and spatial resolution and cycling rate. Hildebrand and Nagle, U of Chicago, reported Liquid Hydrogen minimum ionizing particle boiling in August 1953. John Wood created the 3.7-cm O Liquid Hydrogen BC at LBL in January 1954. By 1959 the Lawrence Berkley Laboratory (LBL) Alvarez group's '72-inch' BC had tracks in liquid hydrogen. Within 10 years bubble chamber volumes increased by a factor of a million and spread to every laboratory with a substantial high-energy physics program. The BC, particle accelerators and special separated particle beams created a new era of High Energy Physics (HEP) experimentation. The BC became the largest most complex cryogenic installation at the world's HEP laboratories for decades. The invention and worldwide development, deployment and characteristics of these cryogenic dynamic target/detectors and related hydrogen targets are described.

  2. Targeted therapy for sarcomas

    PubMed Central

    Forscher, Charles; Mita, Monica; Figlin, Robert

    2014-01-01

    Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing’s sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing’s sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. PMID:24669185

  3. Gelina neutron target optimisation.

    PubMed

    Flaska, M; Plompen, A J M; Mondelaers, W; Lathouwers, D; van der Hagen, T H J J; van Dam, H

    2005-01-01

    A study is being performed on the properties of the Geel Electron Linear Accelerator (GELINA), a powerful white neutron source, designed for the high-energy resolution time-of-flight measurements. The main aim of this study is to reduce the time spread of neutrons of the given energy without compromising the neutron yield. Both time spread and neutron intensity influence the experimental accuracy of high-resolution neutron cross section measurements, which are particularly important in the resonance region. The quantities of interest have been simulated with coupled electron-photon-neutron steady state and transient MCNP4C3 calculations. Following benchmarking of the code to the properties of the existing target, neutron yield, energy spectra, resolution functions, and neutron and heat spatial distributions have been determined for various alternative geometries and materials. At a fixed accelerator power, actinides deliver the highest neutron yield and a small target provides the best time resolution. The resulting high-power density requires a joint optimisation of the thermal hydraulics and neutronics properties. PMID:16381756

  4. Magnetized Target Fusion

    NASA Technical Reports Server (NTRS)

    Griffin, Steven T.

    2002-01-01

    Magnetized target fusion (MTF) is under consideration as a means of building a low mass, high specific impulse, and high thrust propulsion system for interplanetary travel. This unique combination is the result of the generation of a high temperature plasma by the nuclear fusion process. This plasma can then be deflected by magnetic fields to provide thrust. Fusion is initiated by a small traction of the energy generated in the magnetic coils due to the plasma's compression of the magnetic field. The power gain from a fusion reaction is such that inefficiencies due to thermal neutrons and coil losses can be overcome. Since the fusion reaction products are directly used for propulsion and the power to initiate the reaction is directly obtained from the thrust generation, no massive power supply for energy conversion is required. The result should be a low engine mass, high specific impulse and high thrust system. The key is to successfully initiate fusion as a proof-of-principle for this application. Currently MSFC is implementing MTF proof-of-principle experiments. This involves many technical details and ancillary investigations. Of these, selected pertinent issues include the properties, orientation and timing of the plasma guns and the convergence and interface development of the "pusher" plasma. Computer simulations of the target plasma's behavior under compression and the convergence and mixing of the gun plasma are under investigation. This work is to focus on the gun characterization and development as it relates to plasma initiation and repeatability.

  5. Hemolytic uremic syndrome.

    PubMed

    Webster, Kathleen; Schnitzler, Eugene

    2014-01-01

    The thrombotic microangiopathies include both hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Although debate exists as to whether these are separate entities or a spectrum of disease, both result in the clinical picture of thrombocytopenia, hemolytic anemia, and varying degrees of renal and neurologic involvement. Etiology of HUS includes diarrheal infection due to Shiga toxin-producing bacteria, complement deficiency, pneumococcal infection, and cobalamin deficiency. In disease ascribed to TTP, the main etiologic factor is deficiency of an enzyme known as a disintegrin-like and metalloprotease with thrombospondin type 1 repeats, number 13 (ADAMTS-13). The clinical manifestations may vary, but neurologic involvement can be significant, with reports of hypertensive encephalopathy, seizures, thrombosis and infarct. In nondiarrheal forms of disease, recurrence may occur and clinical diagnosis is essential in order to provide a targeted therapy for the suspected etiology. Therapies include supportive care, cobalamin supplementation, as well as plasma infusion and exchange. End stage renal disease may result and transplantation is curative for some forms of the disease. More recent research focuses on targeted immunotherapy to prevent autoantibody prevention. As of yet, there is no one cure for these potentially devastating diseases, and diagnosis and treatment selection presents a challenge to the clinician. PMID:24365375

  6. Robotic Target-Tracking Subsystem

    NASA Technical Reports Server (NTRS)

    Shawaga, Lawrence M.

    1989-01-01

    Position and orientation of target measured in six degrees of freedom. Robotic vision subsystem measures relative position and orientation of specially designed target. Uses standard image-processing algorithms implemented directly in circuitry instead of computer programs. This feature makes it possible to extract complete sets of target-tracking data from successive image frames at rate of 30 frames per second. Five bright circles of target positioned in such way that video images of them processed into data on position and orientation of target relative to camera. Subsystem useful in industrial assembly operation requiring automatic joining of parts initially oriented and moving randomly.

  7. Target control of complex networks

    PubMed Central

    Gao, Jianxi; Liu, Yang-Yu; D'Souza, Raissa M.; Barabási, Albert-László

    2014-01-01

    Controlling large natural and technological networks is an outstanding challenge. It is typically neither feasible nor necessary to control the entire network, prompting us to explore target control: the efficient control of a preselected subset of nodes. We show that the structural controllability approach used for full control overestimates the minimum number of driver nodes needed for target control. Here we develop an alternate ‘k-walk’ theory for directed tree networks, and we rigorously prove that one node can control a set of target nodes if the path length to each target node is unique. For more general cases, we develop a greedy algorithm to approximate the minimum set of driver nodes sufficient for target control. We find that degree heterogeneous networks are target controllable with higher efficiency than homogeneous networks and that the structure of many real-world networks are suitable for efficient target control. PMID:25388503

  8. Targeting Histone Demethylases

    PubMed Central

    Rotili, Dante; Mai, Antonello

    2011-01-01

    In addition to genetic disorders, epigenetic alterations have been shown to be involved in cancer, through misregulation of histone modifications. Miswriting, misreading, and mis-erasing of histone acetylation as well as methylation marks can be actually associated with oncogenesis and tumor proliferation. Historically, methylation of Arg and Lys residues has been considered a stable, irreversible process due to the slow turnover of methyl groups in chromatin. The discovery in recent years of a large number of histone Lys demethylases (KDMs, belonging to either the amino oxidase or the JmjC family) totally changed this point of view and suggested a new role for dynamic histone methylation in biological processes. Since overexpression, alteration, or mutation of a number of KDMs has been found in many types of cancers, such enzymes could represent diagnostic tools as well as epigenetic targets to modulate for obtaining novel therapeutic weapons against cancer. The first little steps in this direction are described here. PMID:21941621

  9. Targeting the glycoproteome.

    PubMed

    Nilsson, Jonas; Halim, Adnan; Grahn, Ammi; Larson, Göran

    2013-02-01

    Despite numerous original publications describing the structural complexity of N- and O-linked glycans on glycoproteins, only very few answer the basic question of which particular glycans are linked to which amino acid residues along the polypeptide chain. Such structural information is of fundamental importance for understanding the biological roles of complex glycosylations as well as deciphering their non-template driven biosynthesis. This review focuses on presenting and commenting on recent strategies, specifically aimed at identifying the glycoproteome of cultured cells and biological samples, using targeted and global enrichment procedures and utilizing the high resolution power, high through-put capacity and complementary fragmentation techniques of tandem mass spectrometry. The goal is to give an update of this emerging field of protein and glyco-sciences and suggest routes to bridge the data gap between the two aspects of glycoprotein characteristics, i.e. glycan structures and their attachment sites. PMID:22886069

  10. ORION laser target diagnostics

    SciTech Connect

    Bentley, C. D.; Edwards, R. D.; Andrew, J. E.; James, S. F.; Gardner, M. D.; Comley, A. J.; Vaughan, K.; Horsfield, C. J.; Rubery, M. S.; Rothman, S. D.; Daykin, S.; Masoero, S. J.; Palmer, J. B.; Meadowcroft, A. L.; Williams, B. M.; Gumbrell, E. T.; Fyrth, J. D.; Brown, C. R. D.; Hill, M. P.; Oades, K. [Plasma Physics Department, Atomic Weapons Establishment, Aldermaston, Reading, Berkshire RG7 4PR (United Kingdom); and others

    2012-10-15

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  11. Electromagnetic targeting of guns

    SciTech Connect

    Pogue, E.W.; Boat, R.M.; Holden, D.N.; Lopez, J.R. [and others

    1996-10-01

    This is the final report of a one-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Electromagnetic pulse (EMP) signals produced from explosives being fired have been reported in the literature for fifty years. When a gun is fired it produces an EMP muzzle blast signal. The strength and nature of these signals was first analyzed in the early 1970s, while the results were interesting, no follow-up studies were conducted. With modern detection and signal processing technology, we believe that these signals could be used to instantaneously locate guns of virtually all calibers as they fire. The objective of our one-year project was to establish the basic nature of these signals and their utility in the concept of electromagnetic targeting of guns.

  12. Targeting neutrophils in sepsis.

    PubMed

    Sônego, Fabiane; Alves-Filho, José Carlos; Cunha, Fernando Queiróz

    2014-08-01

    Sepsis continues to have a high mortality rate worldwide. The multi-step effects of this syndrome make it difficult to develop a comprehensive understanding of its pathophysiology and to identify a direct treatment. Neutrophils play a major role in controlling infection. Interestingly, the recruitment of these cells to an infection site is markedly reduced in severe sepsis. The systemic activation of Toll-like receptors and high levels of TNF-? and nitric oxide are involved in the reduction of neutrophil recruitment due to down-regulation of CXCR2 in neutrophils. By contrast, CCR2 is expressed in neutrophils after sepsis induction and contributes to their recruitment to organs far from the infection site, which contributes to organ damage. This review provides an overview of the recent advances in the understanding of the role of neutrophils in sepsis, highlighting their potential as a therapeutic target. PMID:24867165

  13. Carbon Monoxide Targeting Mitochondria

    PubMed Central

    Queiroga, Cláudia S. F.; Almeida, Ana S.; Vieira, Helena L. A.

    2012-01-01

    Mitochondria present two key roles on cellular functioning: (i) cell metabolism, being the main cellular source of energy and (ii) modulation of cell death, by mitochondrial membrane permeabilization. Carbon monoxide (CO) is an endogenously produced gaseoustransmitter, which presents several biological functions and is involved in maintaining cell homeostasis and cytoprotection. Herein, mitochondrion is approached as the main cellular target of carbon monoxide (CO). In this paper, two main perspectives concerning CO modulation of mitochondrial functioning are evaluated. First, the role of CO on cellular metabolism, in particular oxidative phosphorylation, is discussed, namely, on: cytochrome c oxidase activity, mitochondrial respiration, oxygen consumption, mitochondrial biogenesis, and general cellular energetic status. Second, the mitochondrial pathways involved in cell death inhibition by CO are assessed, in particular the control of mitochondrial membrane permeabilization. PMID:22536507

  14. Target detection portal

    DOEpatents

    Linker, Kevin L. (Albuquerque, NM); Brusseau, Charles A. (Tijeras, NM)

    2002-01-01

    A portal apparatus for screening persons or objects for the presence of trace amounts of target substances such as explosives, narcotics, radioactive materials, and certain chemical materials. The portal apparatus can have a one-sided exhaust for an exhaust stream, an interior wall configuration with a concave-shape across a horizontal cross-section for each of two facing sides to result in improved airflow and reduced washout relative to a configuration with substantially flat parallel sides; air curtains to reduce washout; ionizing sprays to collect particles bound by static forces, as well as gas jet nozzles to dislodge particles bound by adhesion to the screened person or object. The portal apparatus can be included in a detection system with a preconcentrator and a detector.

  15. Targeting HER2

    PubMed Central

    Wong, Karen J; Baidoo, Kwamena E; Nayak, Tapan K; Regino, Celeste AS; Garmestani, Kayhan; Brechbiel, Martin W

    2010-01-01

    The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A?-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of 111In-trastuzumab by melanoma (A375) s.c. xenografts and 111In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected 111In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of 111In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by ?-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected 111In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama. PMID:20716957

  16. Target support for inertial confinement fusion

    SciTech Connect

    Schultz, K.R.

    1995-08-01

    General Atomics (GA) plays an important industrial support role for the US Inertial Confinement Fusion (ICF) program in the area of target technology. This includes three major activities: target fabrication support, target handling systems development, and target chamber design. The work includes target fabrication for existing ICF experiments, target and target system development for future experiments, and target research and target chamber design for experiments on future machines, such as the National Ignition Facility (NIF).

  17. Immunotherapy Targets in Pediatric Cancer

    PubMed Central

    Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

    2011-01-01

    Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer. PMID:22645714

  18. The OLYMPUS internal hydrogen target

    NASA Astrophysics Data System (ADS)

    Bernauer, J. C.; Carassiti, V.; Ciullo, G.; Henderson, B. S.; Ihloff, E.; Kelsey, J.; Lenisa, P.; Milner, R.; Schmidt, A.; Statera, M.

    2014-08-01

    An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

  19. Multiple target laser ablation system

    DOEpatents

    Mashburn, Douglas N. (Knoxville, TN)

    1996-01-01

    A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film.

  20. Multiple target laser ablation system

    DOEpatents

    Mashburn, D.N.

    1996-01-09

    A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film. 3 figs.

  1. Targetability of human disease genes.

    PubMed

    Sakharkar, Meena K; Sakharkar, Kishore R

    2007-06-01

    The availability of complete genome sequences and the wealth of large-scale biological datasets provide an unprecedented opportunity to elucidate the genetic basis of human diseases. Therapeutically relevant targets should be both 'druggable' and 'disease modifying'. In this review we examine the application of computational biology towards the exploration of druggability, targetability and evolutionary conservation of human disease genes. These analyses could have a tremendous potential for systematic in silico drug target identification in the post-genomic era. PMID:17630928

  2. Windowless solid hydrogen target

    NASA Astrophysics Data System (ADS)

    Ishimoto, S.; Kobayashi, T.; Morimoto, K.; Nomura, I.; Ozawa, A.; Suzuki, S.; Takahashi, Y.; Tanihata, I.; Tsuru, T.

    2002-03-01

    A windowless solid hydrogen target has been successfully developed for RI-beam-induced nuclear reactions in the RIKEN RI Beam Facility. Hydrogen crystals of high quality were grown reproducibly in a cell bored in a 10 mm thick pure copper plate which was in direct contact with a liquid helium reservoir. Normal hydrogen gas was crystallized directly on the cell wall between 4.7 and 7.3 K. The diameter of the crystal was 25 mm and the thickness was chosen to be either 5 or 10 mm. After crystallization, sidewalls of the cell were separated from both the crystal and cell plate, and removed to a remote position inside a cryostat. Thus, the crystal was self-supported in the cell without any extra material in its neighborhood. No damage was observed in the separating process. The observed hydrogen pressure indicated the crystal temperature of 4.3 K, when the liquid helium reservoir was at 4.2 K, in agreement with the temperature estimated from the heat balance in the crystal. It shows that we can put the crystal temperature close to the reservoir temperature, though we could not confirm the crystal temperature when the reservoir temperature was reduced to 3 K. Hydrogen sublimation rate was calculated from the vapor pressure and pumping condition. The sublimation loss is negligibly small if the crystal is held at 3 K.

  3. Targeted nanotechnology for cancer imaging.

    PubMed

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B; Karathanasis, Efstathios

    2014-09-30

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

  4. Multisource fusion for target detection

    NASA Astrophysics Data System (ADS)

    Izraelevitz, David; Cochand, Jeffrey A.

    1990-11-01

    An approach to the fusion of information from airborne sensors for the purpose of target detection is described. This approach differs from alternate strategies in that the fusion occurs at the target hypothesis level, a symbolic level, rather than at the sensor level, i.e., candidate target coordinates are merged into correlated target hypotheses. Thus, a source in this approach consists of both a sensor which provides data about the target environment, and a list of candidate target coordinates generated as output from a target detection algorithm. The fusion algorithm is based on generating a statistical model for the detection and false alarm performance of each target coordinate source. Special emphasis is placed on modeling the positional misregistration which occurs when imagery is extracted from different platforms. An iterative clustering algorithm is derived from the source models based on a maximum likelihood target location estimation approach. Results of multisource fusion on several synthetic datasets are provided which indicate the encouraging performance of the system even under severe clutter and sensor misregistration conditions.

  5. Data Mining for Target Marketing

    NASA Astrophysics Data System (ADS)

    Levin, Nissan; Zahavi, Jacob

    Targeting is the core of marketing management. It is concerned with offering the right product/service to the customer at the right time and using the proper channel. In this chapter we discuss how Data Mining modeling and analysis can support targeting applications. We focus on three types of targeting models: continuous-choice models, discrete-choice models and in-market timing models, discussing alternative modeling for each application and decision making. We also discuss a range of pitfalls that one needs to be aware of in implementing a data mining solution for a targeting problem.

  6. Target-directed catalytic metallodrugs

    PubMed Central

    Joyner, J.C.; Cowan, J.A.

    2013-01-01

    Most drugs function by binding reversibly to specific biological targets, and therapeutic effects generally require saturation of these targets. One means of decreasing required drug concentrations is incorporation of reactive metal centers that elicit irreversible modification of targets. A common approach has been the design of artificial proteases/nucleases containing metal centers capable of hydrolyzing targeted proteins or nucleic acids. However, these hydrolytic catalysts typically provide relatively low rate constants for target inactivation. Recently, various catalysts were synthesized that use oxidative mechanisms to selectively cleave/inactivate therapeutic targets, including HIV RRE RNA or angiotensin converting enzyme (ACE). These oxidative mechanisms, which typically involve reactive oxygen species (ROS), provide access to comparatively high rate constants for target inactivation. Target-binding affinity, co-reactant selectivity, reduction potential, coordination unsaturation, ROS products (metal-associated vs metal-dissociated; hydroxyl vs superoxide), and multiple-turnover redox chemistry were studied for each catalyst, and these parameters were related to the efficiency, selectivity, and mechanism(s) of inactivation/cleavage of the corresponding target for each catalyst. Important factors for future oxidative catalyst development are 1) positioning of catalyst reduction potential and redox reactivity to match the physiological environment of use, 2) maintenance of catalyst stability by use of chelates with either high denticity or other means of stabilization, such as the square planar geometric stabilization of Ni- and Cu-ATCUN complexes, 3) optimal rate of inactivation of targets relative to the rate of generation of diffusible ROS, 4) targeting and linker domains that afford better control of catalyst orientation, and 5) general bio-availability and drug delivery requirements. PMID:23828584

  7. The Geometry of Escaping Targets

    Microsoft Academic Search

    E. J. Hilliard; R. F. Pinkos

    1978-01-01

    The escape regions for alerted targets are analytically defined.Sets of circles which circumscribe these regions provide simplified meas of the resulting escape involutes and yield important weapon guidance and sensor search parameters. These regions permit the selection of an aimpoint which incorporates the potential of target maneuers. Applications that illustrate the improved performance of these solutions in missile deployment and

  8. Cancer Cell Targeting Androgen Receptor

    E-print Network

    Liu, Xiaole Shirley

    Cancer Cell Article Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer Min Ni therapies for breast cancer that target the estrogen receptor (ER) are ineffective in the 25%­30% of cases-regulated gene expression in ER­/HER2+ breast cancers we find that AR mediates ligand- dependent activation

  9. Spinning targets for laser fusion

    SciTech Connect

    Baldwin, D.E.; Ryutov, D.D.

    1995-09-01

    Several techniques for spinning the ICF targets up prior to or in the course of their compression are suggested. Interference of the rotational shear flow with Rayleigh-Taylor instability is briefly discussed and possible consequences for the target performance are pointed out.

  10. Killing cells by targeting mitosis

    Microsoft Academic Search

    E Manchado; M Guillamot; M Malumbres

    2012-01-01

    Cell cycle deregulation is a common feature of human cancer. Tumor cells accumulate mutations that result in unscheduled proliferation, genomic instability and chromosomal instability. Several therapeutic strategies have been proposed for targeting the cell division cycle in cancer. Whereas inhibiting the initial phases of the cell cycle is likely to generate viable quiescent cells, targeting mitosis offers several possibilities for

  11. Target identification from radar signatures

    Microsoft Academic Search

    R. Strattan

    1978-01-01

    Modern high resolution radar techniques and real time digital signal processing advances indicate the feasibility of extracting characteristic features of aircraft targets from their radar signatures. Two basic approaches have been suggested. The low frequency approach utilizes harmonically related radar frequencies with wavelengths comparable to the target dimensions. The microwave approach utilizes spread spectrum techniques to achieve high range resolution.

  12. The target strengths of fish

    Microsoft Academic Search

    R. W. G. Haslett

    1969-01-01

    Knowledge of the acoustic target strength of a fish (or of a shoal of fish) is required to enable the performance of present and future sonar equipments to be determined for fish targets. Also, it is hoped that measurement of the strengths and characters of the echoes received from fish will give a reliable guide to the size of the

  13. Molecular Targeting in Pancreatic Cancer

    Microsoft Academic Search

    Scott Wadler

    2007-01-01

    The mortality and morbidity of tumors of the upper GI tract are formidable with incidence and mortality nearly the same. Therefore, better therapies are necessary, and these are generally molecularly targeted therapies. This chapter focuses on the treatment of pancreatic cancer with targeted therapy. Important cellular pathways are reviewed, including signal transduction, proteasome inhibition, cell cycle, anti-angiogenesis pathways, immunologic therapies,

  14. Recent progress in targeting cancer

    PubMed Central

    Demidenko, Zoya N.; McCubrey, James A.

    2011-01-01

    In recent years, numerous new targets have been identified and new experimental therapeutics have been developed. Importantly, existing non-cancer drugs found novel use in cancer therapy. And even more importantly, new original therapeutic strategies to increase potency, selectivity and decrease detrimental side effects have been evaluated. Here we review some recent advances in targeting cancer. PMID:22228887

  15. Dual targeting of peroxisomal proteins

    PubMed Central

    Ast, Julia; Stiebler, Alina C.; Freitag, Johannes; Bölker, Michael

    2013-01-01

    Cellular compartmentalization into organelles serves to separate biological processes within the environment of a single cell. While some metabolic reactions are specific to a single organelle, others occur in more than one cellular compartment. Specific targeting of proteins to compartments inside of eukaryotic cells is mediated by defined sequence motifs. To achieve multiple targeting to different compartments cells use a variety of strategies. Here, we focus on mechanisms leading to dual targeting of peroxisomal proteins. In many instances, isoforms of peroxisomal proteins with distinct intracellular localization are encoded by separate genes. But also single genes can give rise to differentially localized proteins. Different isoforms can be generated by use of alternative transcriptional start sites, by differential splicing or ribosomal read-through of stop codons. In all these cases different peptide variants are produced, of which only one carries a peroxisomal targeting signal. Alternatively, peroxisomal proteins contain additional signals that compete for intracellular targeting. Dual localization of proteins residing in both the cytoplasm and in peroxisomes may also result from use of inefficient targeting signals. The recent observation that some bona fide cytoplasmic enzymes were also found in peroxisomes indicates that dual targeting of proteins to both the cytoplasm and the peroxisome might be more widespread. Although current knowledge of proteins exhibiting only partial peroxisomal targeting is far from being complete, we speculate that the metabolic capacity of peroxisomes might be larger than previously assumed. PMID:24151469

  16. Target Injection By Electrostatic Acceleration

    NASA Astrophysics Data System (ADS)

    Friend, R. K.; Petzoldt, R. W.; Valmianski, E.; Carlson, L.; Stromsoe, J.; Hares, J.

    2008-11-01

    For a direct drive IFE source, the fuel targets must enter the reaction chamber with precise velocity so that they may be accurately irradiated. In this work, a system of electrostatic rings provides acceleration and also enables steering of the target during acceleration. A charge is first placed on the fuel target. Optical fibers mounted on each accelerator electrode trigger a voltage jump in that ring when the target breaks their path. Every third ring will be connected in parallel and accelerating voltage will be advanced as the target passes each electrode. A laser backlights the target along its injection trajectory creating a Poisson spot in the shadow of the fuel target. This spot is used to track the transverse position of the target. Two of the three phases will have rings that are split to allow transverse direction control. Up to ±5 kV accelerating voltage between electrodes will be utilized to achieve 15-20 m/s in 0.9 m.

  17. Targetability of Human Disease Genes

    Microsoft Academic Search

    Meena K. Sakharkar; Kishore R. Sakharkar

    The availability of complete genome sequences and the wealth of large-scale biological datasets provide an un- precedented opportunity to elucidate the genetic basis of human diseases. Therapeutically relevant targets should be both 'druggable' and 'disease modifying'. In this review we examine the application of computational biology towards the ex- ploration of druggability, targetability and evolutionary conservation of human disease genes.

  18. The OPERA experiment Target Tracker

    Microsoft Academic Search

    G. Wilquet; J. Wurtz

    The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead\\/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintilla- tor strips, one per transverse

  19. The OPERA experiment Target Tracker

    Microsoft Academic Search

    T. Adam; E. Baussan; K. Borer; J. E. Campagne; N. Chon-Sen; C. de La Taille; N. Dick; M. Dracos; G. Gaudiot; T. Goeltzenlichter; Y. Gornushkin; J. N. Grapton; J. L. Guyonnet; M. Hess; R. Igersheim; J. Janicsko Csathy; C. Jollet; F. Juget; H. Kocher; A. Krasnoperov; Z. Krumstein; G. Martin-Chassard; U. Moser; A. Nozdrin; A. Olchevski; S. Porokhovoi; L. Raux; A. Sadovski; J. Schuler; H. U. Schütz; C. Schwab; A. Smolnikov; G. Van Beek; P. Vilain; T. Wälchli; G. Wilquet; J. Wurtz

    2007-01-01

    The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead\\/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction.

  20. Radioisotope production targets and modules

    NASA Astrophysics Data System (ADS)

    Johnson, R. R.; Erdman, K.; Gyles, W.; Burbee, J.; Manegoda, A.; Sabaiduc, V.; Kovac, B.; VanLier, E.; Wong, J.; Watt, R.; Wilson, J.; Zyuzin, A.

    2005-12-01

    We have experienced the need to supply full radioisotope production systems that incorporate the accelerator, the beam lines, the targets and the radiochemistry in a unified package. The key component improvements are higher beam currents, more robust production targets, and efficient radiosynthesis modules. This note describes the progress we have made to produce efficient, high yield systems.

  1. Bioinformatics and cancer target discovery

    Microsoft Academic Search

    Brian Desany; Zemin Zhang

    2004-01-01

    The convergence of genomic technologies and the development of drugs designed against specific molecular targets provides many opportunities for using bioinformatics to bridge the gap between biological knowledge and clinical therapy. Identifying genes that have properties similar to known targets is conceptually straightforward. Additionally, genes can be linked to cancer via recurrent genomic or genetic abnormalities. Finally, by integrating large

  2. Manpower Targets and Educational Investments

    ERIC Educational Resources Information Center

    Ritzen, Jo M.

    1976-01-01

    Discusses the use of quadratic programming to calculate the optimal distribution of educational investments required to closely approach manpower targets when financial resources are insufficient to meet manpower targets completely. Demonstrates use of the quadratic programming approach by applying it to the training of supervisory technicians in…

  3. Magnetized target fusion. An overview

    SciTech Connect

    Kirkpatrick, R.C.; Lindemuth, I.R.; Ward, M.S. [Los Alamos National Lab., NM (United States)

    1995-05-01

    The magnetized target fusion (MTF) concept is explained, and the underlying principles are discussed. The necessity of creating a target plasma and the advantage of decoupling its creation from the implosion used to achieve fusion ignition are explained. The Sandia National Laboratories {Phi}-target experiments is one concrete example of the MTF concept, but other experiments have involved some elements of MTF. Lindl-Widner diagrams are used to elucidate the parameter space available to MTF and the physics of MTF ignition. Magnetized target fusion has both limitations and advantages relative to inertial confinement fusion. The chief advantage is that the driver for an MTF target can be orders of magnitude less powerful and intense than what is required for other inertial fusion approaches. A number of critical issues challenge the practical realization of MTF. Past experience, critical issues, and potential integral MTF experiments are discussed. 25 refs., 12 figs.

  4. Targeted marketing and public health.

    PubMed

    Grier, Sonya A; Kumanyika, Shiriki

    2010-01-01

    Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies. PMID:20070196

  5. Unintended events following immunization with MMR: a systematic review.

    PubMed

    Jefferson, Tom; Price, Deirdre; Demicheli, Vittorio; Bianco, Elvira

    2003-09-01

    Public debate over the safety of the trivalent measles, mumps and rubella (MMR) vaccine and the drop in vaccination rates in several countries persists despite its almost universal use and accepted effectiveness. We carried out a systematic review to assess the evidence of unintended effects (beneficial or harmful) associated with MMR and the applicability of systematic reviewing methods to the field of safety evaluation. Eligible studies were comparative prospective or retrospective on healthy individuals up to 15 years of age, carried out or published by 2003. We identified 120 articles satisfying our inclusion criteria and included 22. MMR is associated with a lower incidence of upper respiratory tract infections, a higher incidence of irritability, similar incidence of other adverse effects compared to placebo and is likely to be associated with benign thrombocytopenic purpura (TP), parotitis, joint and limb complaints and aseptic meningitis (mumps Urabe strain-containing MMR). Exposure to MMR is unlikely to be associated with Crohn's disease, ulcerative colitis, autism or aseptic meningitis (mumps Jeryl-Lynn strain-containing MMR). The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunization with MMR cannot be separated from its role in preventing the target diseases. PMID:12922131

  6. IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune conditions

    PubMed Central

    Collin, Mattias; Shannon, Oonagh; Björck, Lars

    2008-01-01

    EndoS from Streptococcus pyogenes efficiently hydrolyzes the functionally important and conserved N-linked glycan of IgG in human blood. Repeated i.v. administration of EndoS in rabbits completely hydrolyzes the glycans of the whole IgG pool, despite the generation of anti-EndoS antibodies. EndoS administration had no apparent effects on the health of the animals. EndoS hydrolysis of the IgG glycan has profound effects on IgG effector functions, such as complement activation and Fc receptor binding, suggesting that the enzyme could be used as an immunomodulatory therapeutic agent against IgG-mediated diseases. We demonstrate here that EndoS indeed has a protective effect in a mouse model of lethal IgG-driven immune (or idiopathic) thrombocytopenic purpura. EndoS pretreatment of pathogenic antibodies inhibits the development of disease, and the enzyme also rescues mice from already established disease when severe thrombocytopenia and s.c. bleeding have developed. These results identify EndoS as a potential therapeutic agent against diseases where pathogenic IgG antibodies are important and further emphasize antibody glycans as possible targets in future therapies against antibody-mediated autoimmune conditions. PMID:18332429

  7. Fecal microbiota transplantation broadening its application beyond intestinal disorders.

    PubMed

    Xu, Meng-Que; Cao, Hai-Long; Wang, Wei-Qiang; Wang, Shan; Cao, Xiao-Cang; Yan, Fang; Wang, Bang-Mao

    2015-01-01

    Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis. PMID:25574083

  8. Role of Siglec-7 in Apoptosis in Human Platelets

    PubMed Central

    Nguyen, Kim Anh; Hamzeh-Cognasse, Hind; Palle, Sabine; Anselme-Bertrand, Isabelle; Arthaud, Charles-Antoine; Chavarin, Patricia; Pozzetto, Bruno; Garraud, Olivier; Cognasse, Fabrice

    2014-01-01

    Background Platelets participate in tissue repair and innate immune responses. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are well-characterized I-type lectins, which control apoptosis. Methodology/Principal Findings We characterized the expression of Siglec-7 in human platelets isolated from healthy volunteers using flow cytometry and confocal microscopy. Siglec-7 is primarily expressed on ? granular membranes and colocalized with CD62P. Siglec-7 expression was increased upon platelet activation and correlated closely with CD62P expression. Cross-linking Siglec-7 with its ligand, ganglioside, resulted in platelet apoptosis without any significant effects on activation, aggregation, cell morphology by electron microscopy analysis or secretion. We show that ganglioside triggered four key pathways leading to apoptosis in human platelets: (i) mitochondrial inner transmembrane potential (??m) depolarization; (ii) elevated expression of pro-apoptotic Bax and Bak proteins with reduced expression of anti-apoptotic Bcl-2 protein; (iii) phosphatidylserine exposure and (iv), microparticle formation. Inhibition of NAPDH oxidase, PI3K, or PKC rescued platelets from apoptosis induced by Siglec-7 recruitment, suggesting that the platelet receptors P2Y1 and GPIIbIIIa are essential for ganglioside-induced platelet apoptosis. Conclusions/Significance The present work characterizes the role of Siglec-7 and platelet receptors in regulating apoptosis and death. Because some platelet pathology involves apoptosis (idiopathic thrombocytopenic purpura and possibly storage lesions), Siglec-7 might be a molecular target for therapeutic intervention/prevention. PMID:25230315

  9. Adult-onset Still's disease-pathogenesis, clinical manifestations, and new treatment options.

    PubMed

    Kadavath, Sabeeda; Efthimiou, Petros

    2015-02-01

    Adult-onset Still's disease (AOSD), a systemic inflammatory disorder, is often considered a part of the spectrum of the better-known systemic-onset juvenile idiopathic arthritis, with later age onset. The diagnosis is primarily clinical and necessitates the exclusion of a wide range of mimicking disorders. AOSD is a heterogeneous entity, usually presenting with high fever, arthralgia, skin rash, lymphadenopathy, and hepatosplenomegaly accompanied by systemic manifestations. The diagnosis is clinical and empirical, where patients are required to meet inclusion and exclusion criteria with negative immunoserological results. There are no clear-cut diagnostic radiological or laboratory signs. Complications of AOSD include transient pulmonary hypertension, macrophage activation syndrome, diffuse alveolar hemorrhage, thrombotic thrombocytopenic purpura and amyloidosis. Common laboratory abnormalities include neutrophilic leukocytosis, abnormal liver function tests, and elevated acute-phase reactants (ESR, CRP, ferritin). Treatment consists of anti-inflammatory medications. Non-steroidal anti-inflammatory drugs have limited efficacy, and corticosteroid therapy and disease-modifying anti-rheumatic drugs are usually required. Recent advances have revealed a pivotal role of proinflammatory cytokines such as tumor necrosis factor-? (TNF-?), interleukin (IL)-1, IL-6, IL-8, and IL-18 in disease pathogenesis, giving rise to the development of novel targeted therapies aiming at optimal disease control. The review aims to summarize recent advances in pathophysiology and potential therapeutic strategies in AOSD. PMID:25613167

  10. Fecal microbiota transplantation broadening its application beyond intestinal disorders

    PubMed Central

    Xu, Meng-Que; Cao, Hai-Long; Wang, Wei-Qiang; Wang, Shan; Cao, Xiao-Cang; Yan, Fang; Wang, Bang-Mao

    2015-01-01

    Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson’s disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis. PMID:25574083

  11. Clinical application of partial splenic embolization.

    PubMed

    Guan, Yong-Song; Hu, Ying

    2014-01-01

    Partial splenic embolization (PSE) is one of the intra-arterial therapeutic approaches of diseases. With the development of interventional radiology, the applications of PSE in clinical practice are greatly extended, while various materials are developed for embolization use. Common indications of PSE include hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia, autoimmune hemolytic anemia, splenic trauma, idiopathic thrombocytopenic purpura, splenic hemangioma, and liver cancer. It is also performed to exclude splenic artery aneurysms from the parent vessel lumen and prevent aneurysm rupture, to treat splenic artery steal syndrome and improve liver perfusion in liver transplant recipients, and to administer targeted treatment to areas of neoplastic disease in the splenic parenchyma. Indicators of the therapeutic effect evaluation of PSE comprise blood routine test, changes in hemodynamics and in splenic volume. Major complications of PSE include the pulmonary complications, severe infection, damages of renal and liver function, and portal vein thrombosis. The limitations of PSE exist mainly in the difficulties in selecting the arteries to embolize and in evaluating the embolized volume. PMID:25538966

  12. Pathology Case Study: Fever, Purpura and Hypotension

    NSDL National Science Digital Library

    Anhalt, John P.

    The Department of Pathology at the University of Pittsburgh Medical Center has compiled a wide range of pathology case studies to aid students and instructors in the medical/health science field. In this case, a 20 year old male college student is admitted to the emergency room with "general malaise, low-grade fever, and purplish discoloration on his face. Using the information provided, which includes patient and social history, images and descriptions from his physical exam, the hospital course and microscopic images, students are encouraged to test their knowledge of pathology and diagnose the patient's medical condition. You can check your diagnosis against the official conclusions in the "Final Diagnosis" section. This is an excellent resource for providing students experience with patient history, lab results and diagnostics.

  13. Aided targeting system simulation evaluation

    NASA Technical Reports Server (NTRS)

    Demaio, Joe; Becker, Curtis

    1994-01-01

    Simulation research was conducted at the Crew Station Research and Development Facility on the effectiveness and ease of use of three targeting systems. A manual system required the aviator to scan a target array area with a simulated second generation forward looking infrared (FLIR) sensor, locate and categorize targets, and construct a target hand-off list. The interface between the aviator and the system was like that of an advanced scout helicopter (manual mode). Two aided systems detected and categorized targets automatically. One system used only the FLIR sensor and the second used FLIR fused with Longbow radar. The interface for both was like that of an advanced scout helicopter aided mode. Exposure time while performing the task was reduced substantially with the aided systems, with no loss of target hand-off list accuracy. The fused sensor system showed lower time to construct the target hand-off list and a slightly lower false alarm rate than the other systems. A number of issues regarding system sensitivity and criterion, and operator interface design are discussed.

  14. Target identification with Bayesian networks

    NASA Astrophysics Data System (ADS)

    Hautaniemi, Sampsa K.; Korpisaari, Petri T.; Saarinen, Jukka P. P.

    2000-04-01

    Tracking algorithms can tell fairly reliable where target is heading. That is enough in civilian aviation, but in defence applications it might be not. Target's type and its hostility are at least as important. Normally, identification of type or friend or foe cannot be determined from target's kinematic information. To identify a target we also need other information. Every plane type has its own specialities e.g. we know that certain type has two engines which affects directly to heat of exhaust fumes. This kind of speciality is generally referred as an attribute information. Because attribute information is type depended, it must be modelled by an expert, who has beforehand knowledge of the target's causality relations. One of the best theories to get expert's knowledge into a tracking system is Bayesian networks. Bayesian networks is a model that describes relationships between attributes. In this paper we concentrate to identification problem. Question is how comprehension of the target's type changes with time when observations are corrupted by noise. We illustrate theory of Bayesian networks and explain its place in racking system. Finally we analyze performance of Bayesian networks in case where the problem is to identify targets from noisy data set.

  15. Development of targeted radiotherapy systems

    NASA Astrophysics Data System (ADS)

    Ferro, Guillermina; Murphy, Consuelo A.; Villarreal, José E.; Pedraza, Martha; García, Laura; Tendilla, José I.; Paredes, Lydia

    2001-10-01

    Conventional or external beam radiotherapy, has been a viable alternative for cancer treatment. Although this technique is effective, its use is limited if the patient has multiple malignant lesions (metastases). An alternative approach is based on the design of radiopharmaceuticals that, to be administered in the patient, are directed specifically toward the target cell producing a selective radiation delivery. This treatment is known as targeted radiotherapy. We have summarized and discussed some results related to our investigations on the development of targeted radiotherapy systems, including aspects of internal dosimetry.

  16. Targeting the p53 Pathway

    PubMed Central

    Golubovskaya, Vita M.; Cance, William G.

    2013-01-01

    SYNOPSIS This review summarizes data on translational studies to target the p53 pathway in cancer. It describes the functions of the p53 and Mdm-2 signaling pathways and discusses current therapeutic approaches to target p53 pathways, including reactivation of p53. In addition, direct interaction and colocalization of the p53 and focal adhesion kinase (FAK) proteins in cancer cells have been demonstrated, and different approaches to target this interaction are reviewed. In summary, this is a broad review of p53 function as it relates to the diagnosis and treatment of a broad range of cancers. PMID:24012397

  17. Cancer Target Discovery and Development

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > CTD² Cancer Target Discovery and Development [1] Program Body:  Network Centers The CTD2 Network Centers work both independently and collaboratively to advance the understanding of

  18. "Cavitation in a Mercury Target"

    SciTech Connect

    West, C.D.

    2000-09-06

    Recent theoretical work on the formation of bubble nucleation centers by energetic particles leads to some reasonably credible calculations of the maximum negative pressure that might be sustained without bubble formation in the mercury target of the Spallation Neutron Source.

  19. Nanoparticles for Targeted Drug Delivery

    E-print Network

    Chow, Gan-Moog

    Nanoparticles were synthesized and modified for target drug delivery. The research involved the aqueous synthesis of near infrared (NIR) sensitive Au-Au2S nanoparticles. An anti-cancer drug (cis-platin) ...

  20. Space Telescope moving target tracking

    NASA Technical Reports Server (NTRS)

    Strikwerda, T. E.; Strohbehn, K.; Fowler, K. R.; Skillman, D. R.

    1985-01-01

    This paper formulates a Space Telescope (ST) moving target tracking algorithm and evaluates a practical implementation. The algorithm is shown to be satisfactory for tracking such moving objects as the moons of Mars.

  1. Ion beam inertial confinement target

    DOEpatents

    Bangerter, Roger O. (Danville, CA); Meeker, Donald J. (Livermore, CA)

    1985-01-01

    A target for implosion by ion beams composed of a spherical shell of frozen DT surrounded by a low-density, low-Z pusher shell seeded with high-Z material, and a high-density tamper shell. The target has various applications in the inertial confinement technology. For certain applications, if desired, a low-density absorber shell may be positioned intermediate the pusher and tamper shells.

  2. Strings with discrete target space

    Microsoft Academic Search

    Ivan K. Kostov; Service de Physique Theorique

    1992-01-01

    We investigate the field theory of strings having as a target space an\\u000aarbitrary discrete one-dimensional manifold. The existence of the continuum\\u000alimit is guaranteed if the target space is a Dynkin diagram of a simply laced\\u000aLie algebra or its affine extension. In this case the theory can be mapped onto\\u000athe theory of strings embedded in the infinite

  3. Chloride channels as drug targets

    Microsoft Academic Search

    Luis J. V. Galietta; Alan S. Verkman

    2008-01-01

    Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets. Chloride channels are involved in a wide range of biological functions, including epithelial fluid secretion, cell-volume regulation, neuroexcitation, smooth-muscle contraction and acidification of intracellular organelles. Mutations in several chloride channels cause human

  4. Targeted therapy in gastric cancer.

    PubMed

    Thiel, Alexandra; Ristimäki, Ari

    2015-05-01

    Gastric cancer is often diagnosed at an advanced stage. Although chemotherapy prolongs survival and improves quality of life, the survival of gastric cancer patients with advanced disease is short. Thanks to recent insights into the molecular pathways involved in gastric carcinogenesis, new targeted treatment options have become available for gastric cancer patients. Trastuzumab, an antibody targeted to HER-2, was shown to improve survival of advanced gastric cancer patients harboring HER-2 overexpression due to gene amplification in their tumor cells, and is currently also explored in adjuvant and neoadjuvant settings. Another agent with promising results in clinical trials is ramucirumab, an antibody targeting VEGFR-2. No clear survival benefit, however, were experienced with agents targeting EGFR (cetuximab, panitumumab), VEGF-A (bevacizumab), or mTOR (everolimus). Drugs targeting c-MET/HGF are currently under investigation in biomarker-selected cohorts, with promising results in early clinical trials. This review will summarize the current status of targeted treatment options in gastric cancer. PMID:25706252

  5. Inflation targeting as a monetary policy rule

    Microsoft Academic Search

    Lars E. O. Svensson

    1999-01-01

    The purpose of the paper is to survey and discuss inflation targeting in the context of monetary policy rules. The paper provides a general conceptual discussion of monetary policy rules, attempts to clarify the essential characteristics of inflation targeting, compares inflation targeting to monetary targeting and nominal-GDP targeting, and draws some conclusions for the monetary policy of the European System

  6. LBNE Target Hall Instrumentation January 27, 2010

    E-print Network

    McDonald, Kirk

    stack produced high-contrast features Gap between baffle and target Horizontal fin · Beam was scanned · Electrically isolated target · Proton beam kicks off electrons and other charge particles from target segments targets #12;8 · Cross-hairs intercept primary proton beam Target must be out Beam also scatters on Horn

  7. Detecting slow moving targets in SAR images

    Microsoft Academic Search

    Robert Linnehan; Leonid Perlovsky; Chris W. Mutz; John Schindler

    2004-01-01

    Ground moving target indication (GMTI) radars can detect slow-moving targets if their velocities are high enough to produce distinguishable Doppler frequencies. However, no reliable technique is currently available to detect targets that fall below the minimum detectable velocity (MDV) of GMTI radars. In synthetic aperture radar (SAR) images, detection of moving targets is difficult because of target smear due to

  8. Unification of automatic target tracking and automatic target recognition

    NASA Astrophysics Data System (ADS)

    Schachter, Bruce J.

    2014-06-01

    The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT?ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

  9. Targets and methods for target preparation for radionuclide production

    DOEpatents

    Zhuikov, Boris L; Konyakhin, Nicolai A; Kokhanyuk, Vladimir M; Srivastava, Suresh C

    2012-10-16

    The invention relates to nuclear technology, and to irradiation targets and their preparation. One embodiment of the present invention includes a method for preparation of a target containing intermetallic composition of antimony Ti--Sb, Al--Sb, Cu--Sb, or Ni--Sb in order to produce radionuclides (e.g., tin-117 m) with a beam of accelerated particles. The intermetallic compounds of antimony can be welded by means of diffusion welding to a copper backing cooled during irradiation on the beam of accelerated particles. Another target can be encapsulated into a shell made of metallic niobium, stainless steel, nickel or titanium cooled outside by water during irradiation. Titanium shell can be plated outside by nickel to avoid interaction with the cooling water.

  10. Optimum Polarization for Foliage Camouflaged Target Discrimination

    E-print Network

    Sarabandi, Kamal

    Optimum Polarization for Foliage Camouflaged Target Discrimination Using a Genetic Algorithm camouflaged target detection at low microwave frequencies is investigated, using a powerful foliage and hard. Based on fully polarimetric simulation results of a foliage camouflaged metallic target a polarization

  11. Watch TARGET Presentations from AACR 2013

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > Watch TARGET Presentations from AACR 2013 Watch TARGET Presentations from AACR 2013 [1] April 07, 2013 TARGET researchers presented their work on pediatric cancers at the AACR Annual

  12. Watch TARGET Presentations from AACR 2013

    Cancer.gov

    Published on Office of Cancer Genomics (https://ocg.cancer.gov) Home > Watch TARGET Presentations from AACR 2013 Watch TARGET Presentations from AACR 2013 [1] April 07, 2013 TARGET researchers presented their work on pediatric cancers at the AACR Annual

  13. Molecular targets underlying general anaesthesia

    PubMed Central

    Franks, Nicholas P

    2006-01-01

    The discovery of general anaesthesia, over 150 years ago, revolutionised medicine. The ability to render a patient unconscious and insensible to pain made modern surgery possible and general anaesthetics have become both indispensible as well as one of the most widely used class of drugs. Their extraordinary chemical diversity, ranging from simple chemically inert gases to complex barbiturates, has baffled pharmacologists, and ideas about how they might work have been equally diverse. Until relatively recently, thinking was dominated by the notion that anaesthetics acted ‘nonspecifically' by dissolving in the lipid bilayer portions of nerve membranes. While this simple idea could account for the chemical diversity of general anaesthetics, it has proven to be false and it is now generally accepted that anaesthetics act by binding directly to sensitive target proteins. For certain intravenous anaesthetics, such as propofol and etomidate, the target has been identified as the GABAA receptor, with particular subunits playing a crucial role. For the less potent inhalational agents, the picture is less clear, although a relatively small number of targets have been identified as being the most likely candidates. In this review, I will describe the work that led up to the identification of the GABAA receptor as the key target for etomidate and propofol and contrast this with current progress that has been made in identifying the relevant targets for other anaesthetics, particularly the inhalational agents. PMID:16402123

  14. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  15. A Cryogenic Infrared Calibration Target

    NASA Technical Reports Server (NTRS)

    Wollack, E. J.; Kinzer, R. E., Jr.; Rinehart, S. A.

    2014-01-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R < or = 0.003, from 800 to 4800/cm (12 - 2 microns ). Upon expanding the spectral range under consideration to 400-10,000/ cm-1 (25 - 1 microns) the observed performance gracefully degrades to R < or = 0.02 at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to approx.4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials-Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder-are characterized and presented

  16. STIS Target Acquisitions During SMOV

    NASA Astrophysics Data System (ADS)

    Katsanis, Rocio M.; Downes, Ron; Hartig, George; Kraemer, Steve

    1997-07-01

    We summarize the first results on the analysis of in-flight STIS target acquisition (ACQ and ACQ/PEAK). These results show that the STIS target acquisition (ACQ) is working very accurately for point sources (within 0.5 pixels = 0.025 arcseconds), about 4 times better than specified in the Instrument Handbook. As a result of the accuracy of the ACQ algorithm, we are no longer recommending to perform ACQ/PEAKs for the 0.2 arcsecond wide slits. For diffuse acquisitions the accuracy varies with target size. Although analysis of ACQ/PEAK data is hampered by a flight software problem, we anticipate that peakups will be accurate to roughly ±5% of the slit width (instead of the ±15% pr eviously advertised). We are implementing several enhancements to the flight software that will take effect by mid- August to improve the quality of the acquisitions.

  17. Clinical Biomarkers for Hypoxia Targeting

    PubMed Central

    Le, Quynh-Thu; Courter, Don

    2010-01-01

    Tumor hypoxia or a reduction of the tissue oxygen tension is a key microenvironmental factor for tumor progression and treatment resistance in solid tumors. Because hypoxic tumor cells have been demonstrated to be more resistant to ionizing radiation, hypoxia has been a focus of laboratory and clinical research in radiation therapy for many decades. It is believed that proper detection of hypoxic regions would guide treatment options and ultimately improve tumor response. To date, most clinical efforts in targeting tumor hypoxia have yielded equivocal results due to the lack of appropriate patient selection. However, with improved understanding of the molecular pathways regulated by hypoxia and the discovery of novel hypoxia markers, the prospect of targeting hypoxia has become more tangible. This chapter will focus on the development of clinical biomarkers for hypoxia targeting. PMID:18483785

  18. Observations of Spacecraft Targets, Unusual Asteroids, and Targets of Opportunity

    NASA Technical Reports Server (NTRS)

    Tholen, David J.

    1998-01-01

    Obtain physical and astrometric observations of: (1) spacecraft targets to support mission operations; (2) known asteroids with unusual orbits to help determine their origin; and (3) newly discovered minor planets (including both asteroids and comets) that represent a particular opportunity to add significant new knowledge of the Solar System.

  19. Targeting antibodies to the cytoplasm

    PubMed Central

    Marschall, Andrea L J; Frenzel, André; Schirrmann, Thomas; Schüngel, Manuela

    2011-01-01

    A growing number of research consortia are now focused on generating antibodies and recombinant antibody fragments that target the human proteome. A particularly valuable application for these binding molecules would be their use inside a living cell, e.g., for imaging or functional intervention. Animal-derived antibodies must be brought into the cell through the membrane, whereas the availability of the antibody genes from phage display systems allows intracellular expression. Here, the various technologies to target intracellular proteins with antibodies are reviewed. PMID:21099369

  20. Targeting cancer using cholesterol conjugates

    PubMed Central

    Radwan, Awwad A.; Alanazi, Fares K.

    2013-01-01

    Conjugation of cholesterol moiety to active compounds for either cancer treatment or diagnosis is an attractive approach. Cholesterol derivatives are widely studied as cancer diagnostic agents and as anticancer derivatives either in vitro or in vivo using animal models. In largely growing studies, anticancer agents have been chemically conjugated to cholesterol molecules, to enhance their pharmacokinetic behavior, cellular uptake, target specificity, and safety. To efficiently deliver anticancer agents to the target cells and tissues, many different cholesterol–anticancer conjugates were synthesized and characterized, and their anticancer efficiencies were tested in vitro and in vivo. PMID:24493968

  1. The OPERA experiment Target Tracker

    E-print Network

    Adam, T

    2007-01-01

    The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described.

  2. The OPERA experiment Target Tracker

    NASA Astrophysics Data System (ADS)

    Adam, T.; Baussan, E.; Borer, K.; Campagne, J.-E.; Chon-Sen, N.; de La Taille, C.; Dick, N.; Dracos, M.; Gaudiot, G.; Goeltzenlichter, T.; Gornushkin, Y.; Grapton, J.-N.; Guyonnet, J.-L.; Hess, M.; Igersheim, R.; Janicsko Csathy, J.; Jollet, C.; Juget, F.; Kocher, H.; Krasnoperov, A.; Krumstein, Z.; Martin-Chassard, G.; Moser, U.; Nozdrin, A.; Olchevski, A.; Porokhovoi, S.; Raux, L.; Sadovski, A.; Schuler, J.; Schütz, H.-U.; Schwab, C.; Smolnikov, A.; Van Beek, G.; Vilain, P.; Wälchli, T.; Wilquet, G.; Wurtz, J.

    2007-07-01

    The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described.

  3. Splenectomy for haematological disorders.

    PubMed

    Jankulovski, N; Antovic, S; Kuzmanovska, B; Mitevski, A

    2014-01-01

    (Full text is available at http://www.manu.edu.mk/prilozi). Splenectomy is therapeutic for a large host of conditions. It is a consequence of expanding the list of disorders and liberalizing the indications for splenectomy in many diseases. Red blood cells disorders: autoimmune hemolytic anemia, hereditary spherocytosis, hemoglobinopathies and thalassemia are prone to splenectomy after failure of medical therapy. A variety of thrombocytopenic disorders are improved by splenectomy, and the most common indication for splenectomy is ITP (idiopathic thrombocytopenic purpura). Splenectomy is successful in reversing hypersplenism in a spectrum of disease called myeloproliferative disorders. Relief of symptoms from splenomegaly is also achieved, but it does not affect the inexorable course of the disorder. The role of splenectomy in white blood cells disorders (leukemias and lymphomas) is only palliative and facilitates chemotherapy. Splenectomy in patients with hemathologic disorders imparts a risk of fulminant and life threatening infection "overwhelming postsplenectomy sepsis" that can be obviated by appropriate treatment. Although splenectomy for hemathologic disorders is only therapeutic and not curative, the relief of symptoms and for some disorders facilitation of chemotherapy leads to better quality of life and longer survival. Key words: Splenectomy, laparoscopic splenectomy, hemathologic dsorders, hereditary spherocytosis, idio-pathic thrombocytopenic purpura, ITP, myeloproliferative disorders, lymphoma, overwhelming posts-plenectomy sepsis. PMID:24798604

  4. Epigenetic modifications as therapeutic targets

    Microsoft Academic Search

    Theresa K Kelly; Daniel D De Carvalho; Peter A Jones

    2010-01-01

    Epigenetic modifications work in concert with genetic mechanisms to regulate transcriptional activity in normal tissues and are often dysregulated in disease. Although they are somatically heritable, modifications of DNA and histones are also reversible, making them good targets for therapeutic intervention. Epigenetic changes often precede disease pathology, making them valuable diagnostic indicators for disease risk or prognostic indicators for disease

  5. Aptamers for Targeted Drug Delivery

    PubMed Central

    Ray, Partha; White, Rebekah R.

    2010-01-01

    Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  6. A variable optical target simulator

    Microsoft Academic Search

    C. E. Kulas; E. D. Crosswhite

    1979-01-01

    A crucial experiment, relative to determining the ability of an imaging seeker to track a target and generate accurate terminal guidance, requires an optical device which can provide imagery that grows in size as a real-time estimate of true missile flight conditions. The basic components of an Optical Contrast TV Imaging Seeker are reviewed to establish the need for an

  7. CEO-Specific Leadership Targets

    ERIC Educational Resources Information Center

    Eadie, Doug

    2004-01-01

    One critical element to maintaining a close, productive and enduring partnership with the governing board is a well-designed and executed process for board evaluation of the superintendent's performance. For the board's evaluation to be a powerful partnership-building tool, it must be based on two sets of performance targets. The two basic steps…

  8. Targeting multidrug resistance in cancer

    Microsoft Academic Search

    Gergely Szakács; Jill K. Paterson; Joseph A. Ludwig; Catherine Booth-Genthe; Michael M. Gottesman

    2006-01-01

    Effective treatment of metastatic cancers usually requires the use of toxic chemotherapy. In most cases, multiple drugs are used, as resistance to single agents occurs almost universally. For this reason, elucidation of mechanisms that confer simultaneous resistance to different drugs with different targets and chemical structures — multidrug resistance — has been a major goal of cancer biologists during the

  9. Magnetized target fusion ignition conditions

    SciTech Connect

    Peretti, M. de; Sabatier, M. [Centre d`Etudes de Limeil-Valenton, Villeneuve St. Georges (France)

    1995-12-31

    Magnetized Target Fusion (MTF) consists of the hydrodynamic compression of a wall, hot, magnetized DT plasma to ignition conditions. MTF takes advantage of two benefits of a magnetic field in a plasma: (1) reduction of the thermal conductivity and (2) enhancement of the charged particle reaction product energy deposition. To study the ignition conditions, the authors evaluate the gains brought by compression and fusion and losses dissipated by bremsstrahlung, compton, conduction and synchrotron. They are able to construct the boundaries for boot-strapping burn with or in absence (ICF) of magnetic field. They demonstrate that MTF ignition can occur using very low implosion velocities for plasmas with very low Rho-R and densities (by ICF standards). This is possible because the major heat loss mechanism, thermal conduction is suppressed by mega-gauss fields and the DT alpha particles are partially trapped within the plasma. They prove, unlike ICF, that the fusion region for MTF is sensitive to the mass of the DT in the target. This sensitivity just reflects the fact that the additional physical processes involved in MTF don`t have the same dependence on density and target radius separately, so the equations don`t scale in such a simple way with Rho-R. For a target containing 10 mu-gm of DT, the MTF region is considerably smaller than for 100 mu-gm, and even the ICF region is hardly enlarged at all.

  10. GABAA receptor target of tetramethylenedisulfotetramine

    E-print Network

    Hammock, Bruce D.

    as a chemical threat agent. TETS is a noncompetitive blocker of the GABA type A receptor (GABAAR), but itsGABAA receptor target of tetramethylenedisulfotetramine Chunqing Zhaoa,1 , Sung Hee Hwangb , Bruce for characterizing the binding sites of high-affinity 14 C radio- ligands. Fourteen noncompetitive antagonists

  11. Polarimetric imaging of underwater targets

    NASA Astrophysics Data System (ADS)

    Gilerson, Alex; Carrizo, Carlos; Tonizzo, Alberto; Ibrahim, Amir; El-Habashi, Ahmed; Foster, Robert; Ahmed, Samir

    2013-06-01

    Underwater imaging is challenging because of the significant attenuation of light due to absorption and scattering of light in water. Using polarization properties of light is one of the options for improving image quality. We present results of imaging of a polarized target in open ocean (Curacao) and coastal (NY Bight) waters. The target in the shape of a square is divided into several smaller squares, each of which is covered with a polarizing film with different polarization orientations or transmission coefficients was placed on a mirror and imaged under water by a green-band full-Stokes polarimetric video camera at the full range of azimuth angles against the Sun. The values of the Stokes vector components from the images are compared with the modeled image of the target using radiative transfer code for the atmosphere-ocean system combined with the simple imaging model. It is shown that even in clear water the impact of the water body on the polarized underwater image is very significant and retrieval of target polarization characteristics from the image is extremely challenging.

  12. Tumor Targeting via Integrin Ligands

    PubMed Central

    Marelli, Udaya Kiran; Rechenmacher, Florian; Sobahi, Tariq Rashad Ali; Mas-Moruno, Carlos; Kessler, Horst

    2013-01-01

    Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side-effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability, and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor-specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug-delivery systems, and discuss the prospects of such therapies to specifically target tumor cells. PMID:24010121

  13. Optimization in target movement simulations

    Microsoft Academic Search

    Anders Eriksson

    2008-01-01

    This paper discusses a methodology for fixed-time simulations of optimal movements of a mechanical system, between specified initial and target configurations, without any a priori knowledge on the trajectory between those. It is primarily aimed at human movement simulations with muscular controls. The basic formulation considers both displacements and forces as unknowns during the movement, connects them, and utilizes a

  14. Guide to Accessing TARGET Data

    Cancer.gov

    Published on Office of Cancer Genomics (https://ocg.cancer.gov) Home > Guide to Accessing TARGET Data   New user?                     Approved user?                [1] [2] [3] What type of data do you want to download: open and/or controlled access data? OPEN

  15. Guide to Accessing TARGET Data

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > Guide to Accessing TARGET Data   New user?                     Approved user?                [1] [2] [3] What type of data do you want to download: open and/or controlled access data? OPEN

  16. Terrain data aided passive ground target tracking

    Microsoft Academic Search

    Chang-Hwan Kim; Keeyoung Choi; Chang-Kyung Ryoo; Kyeong-Dae Park; Jin-Bok Kim; Ki-Sung Kim; Jong-Lae Jo

    2009-01-01

    The primary purpose of passive tracking function is to support weapon systems on the military aircraft. A ground-attacking aircraft must know the precise location of the target to fulfill its missions. The target tracking system must estimate location of the target passively, if the need of stealth performance is highly required. A target is designated using integrated sensors, such as

  17. An algorithm for tracking multiple targets

    Microsoft Academic Search

    D. R. Reid

    1979-01-01

    An algorithm for tracking multiple targets in a cluttered enviroment is developed. The algorithm is capable of initiating tracks, accounting for false or missing reports, and processing sets of dependent reports. As each measurement is received, probabilities are calculated for the hypotheses that the measurement came from previously known targets in a target file, or from a new target, or

  18. Nonsinusoidal radar signal design for stealth targets

    Microsoft Academic Search

    Nasser J. Mohamed

    1995-01-01

    The detection of stealth point targets challenges the design of conventional radars using sinusoidal carriers since the objective of stealth technology is to reduce the radar cross section (RCS) of targets to a level where the radar receiver cannot detect the target. While there are a number of techniques employing different technologies to reduce the RCS of targets, shaping and

  19. Adaptive detection in dense target environments

    Microsoft Academic Search

    W. L. Melvin; J. R. Guerci

    2001-01-01

    We consider the impact of target signals corrupting the covariance estimate when implementing STAP in ground moving target indication (GMTI) scenarios. Herein, we propose a model for seeding the radar data cube with target signals and calculate both asymptotic and finite training data detection losses. In general, both the location and strength of the corruptive target signals influence performance: under

  20. Tracking multiple targets with multifocal attention

    E-print Network

    Cavanagh, Patrick

    Tracking multiple targets with multifocal attention Patrick Cavanagh and George A. Alvarez to track four or more targets simultaneously. Although the mechanisms by which attention maintains contact of the tracking process, including properties defining a `trackable' target, the maximum number of targets

  1. obscuration managment for multiple ground target tracking

    E-print Network

    Paris-Sud XI, Université de

    Terrain obscuration managment for multiple ground target tracking Benjamin Pannetier Information Grenoble, France Email: michele.rombaut@lis.inpg.fr Abstract-- Multiple ground targets tracking with a GMTI to track multiple manoeuvring ground targets. However, the case of undetected targets due to terrain

  2. Digital filters for infrared target acquisition sensors

    Microsoft Academic Search

    J. J. Otazo; E. W. Tung; R. R. Parenti

    1980-01-01

    This paper describes an extension of the linear matched filter concept as it applies to the detection of resolved targets embedded in spatially correlated background clutter. The practical problems associated with the design of filters matched to sets of targets are discussed. The use of multiple or parallel filters for the detection of dissimilar targets or target ensembles is also

  3. A rotating target wheel system for Gammasphere

    NASA Astrophysics Data System (ADS)

    Greene, John P.; Falout, Joseph W.; Lister, Christopher J.; Nardi, Bruce G.; Fox, John D.

    1999-06-01

    A description is given for a low-mass, rotating target wheel to be used within the Gammasphere target chamber. This system was developed for experiments employing high beam currents in order to extend lifetimes of targets using low-melting point target material. The design is based on a previously successful implementation of rotating target wheels for the Argonne Positron Experiment (APEX) as well as the Fragment Mass Analyser (FMA) at ATLAS (Argonne Tandem Linac Accelerator System). A brief history of these rotating target wheel systems is given as well as a discussion on target preparation and performance.

  4. Exploiting target amplitude information to improve multi-target tracking

    NASA Astrophysics Data System (ADS)

    Ehrman, Lisa M.; Blair, W. Dale

    2006-05-01

    Closely-spaced (but resolved) targets pose a challenge for measurement-to-track data association algorithms. Since the Mahalanobis distances between measurements collected on closely-spaced targets and tracks are similar, several elements of the corresponding kinematic measurement-to-track cost matrix are also similar. Lacking any other information on which to base assignments, it is not surprising that data association algorithms make mistakes. One ad hoc approach for mitigating this problem is to multiply the kinematic measurement-to-track likelihoods by amplitude likelihoods. However, this can actually be detrimental to the measurement-to-track association process. With that in mind, this paper pursues a rigorous treatment of the hypothesis probabilities for kinematic measurements and features. Three simple scenarios are used to demonstrate the impact of basing data association decisions on these hypothesis probabilities for Rayleigh, fixed-amplitude, and Rician targets. The first scenario assumes that the tracker carries two tracks but only one measurement is collected. This provides insight into more complex scenarios in which there are fewer measurements than tracks. The second scenario includes two measurements and one track. This extends naturally to the case with more measurements than tracks. Two measurements and two tracks are present in the third scenario, which provides insight into the performance of this method when the number of measurements equals the number of tracks. In all cases, basing data association decisions on the hypothesis probabilities leads to good results.

  5. Effects of target typicality on categorical search

    PubMed Central

    Maxfield, Justin T.; Stalder, Westri D.; Zelinsky, Gregory J.

    2014-01-01

    The role of target typicality in a categorical visual search task was investigated by cueing observers with a target name, followed by a five-item target present/absent search array in which the target images were rated in a pretest to be high, medium, or low in typicality with respect to the basic-level target cue. Contrary to previous work, we found that search guidance was better for high-typicality targets compared to low-typicality targets, as measured by both the proportion of immediate target fixations and the time to fixate the target. Consistent with previous work, we also found an effect of typicality on target verification times, the time between target fixation and the search judgment; as target typicality decreased, verification times increased. To model these typicality effects, we trained Support Vector Machine (SVM) classifiers on the target categories, and tested these on the corresponding specific targets used in the search task. This analysis revealed significant differences in classifier confidence between the high-, medium-, and low-typicality groups, paralleling the behavioral results. Collectively, these findings suggest that target typicality broadly affects both search guidance and verification, and that differences in typicality can be predicted by distance from an SVM classification boundary. PMID:25274990

  6. Effects of target typicality on categorical search.

    PubMed

    Maxfield, Justin T; Stalder, Westri D; Zelinsky, Gregory J

    2014-01-01

    The role of target typicality in a categorical visual search task was investigated by cueing observers with a target name, followed by a five-item target present/absent search array in which the target images were rated in a pretest to be high, medium, or low in typicality with respect to the basic-level target cue. Contrary to previous work, we found that search guidance was better for high-typicality targets compared to low-typicality targets, as measured by both the proportion of immediate target fixations and the time to fixate the target. Consistent with previous work, we also found an effect of typicality on target verification times, the time between target fixation and the search judgment; as target typicality decreased, verification times increased. To model these typicality effects, we trained Support Vector Machine (SVM) classifiers on the target categories, and tested these on the corresponding specific targets used in the search task. This analysis revealed significant differences in classifier confidence between the high-, medium-, and low-typicality groups, paralleling the behavioral results. Collectively, these findings suggest that target typicality broadly affects both search guidance and verification, and that differences in typicality can be predicted by distance from an SVM classification boundary. PMID:25274990

  7. Remote moving target indication assessment

    SciTech Connect

    Canavan, G.H.

    1996-10-01

    The objective of this project was to design and test key components of a sensor to be used on remotely piloted vehicles, aircraft, or satellites for the detection of moving vehicles in cluttered backgrounds. The proposed sensor uses modern large-array focal planes to provide multiple infrared observations of moving targets and capable on-board computers to integrate multiple observations to detect moving targets in background clutter. This combination reduces the size, weight, and cost of the sensor to levels that can be flown on many small unmanned platforms. This effort selected the actual components, integrated them into a test bed, tested the performance of the sensor against realistic generated scenes, and designed a proof-of-concept prototype.

  8. Targeting glutamate synapses in schizophrenia

    PubMed Central

    Field, Julie R.; Walker, Adam G.; Conn, P. Jeffrey

    2011-01-01

    Although early clinical observations implicated dopamine dysfunction in the neuropathology of schizophrenia, accumulating evidence suggests that multiple neurotransmitter pathways are dysregulated. The psychotomimetic actions of NMDA receptor antagonists point to an imbalance of glutamatergic signaling. Encouragingly, numerous preclinical and clinical studies have elucidated several potential targets for increasing NMDA receptor function and equilibrating glutamatergic tone, including the metabotropic glutamate receptors 2, 3 and 5, the muscarinic acetylcholine receptors M1 and M4, and the glycine transporter GlyT1. Highly specific allosteric and orthosteric ligands have been developed that modify the activity of these novel target proteins, and in this review we summarize both the glutamatergic mechanisms and the novel compounds that are increasing promise for a multifaceted pharmacological approach to treat schizophrenia. PMID:21955406

  9. Targeting Wnt Pathways in Disease

    PubMed Central

    Zimmerman, Zachary F.; Moon, Randall T.

    2012-01-01

    Wnt-mediated signal transduction pathways have long been recognized for their roles in regulating embryonic development, and have more recently been linked to cancer, neurologic diseases, inflammatory diseases, and disorders of endocrine function and bone metabolism in adults. Although therapies targeting Wnt signaling are attractive in theory, in practice it has been difficult to obtain specific therapeutics because many components of Wnt signaling pathways are also involved in other cellular processes, thereby reducing the specificity of candidate therapeutics. New technologies, and advances in understanding the mechanisms of Wnt signaling, have improved our understanding of the nuances of Wnt signaling and are leading to promising new strategies to target Wnt signaling pathways. PMID:23001988

  10. KRAS as a Therapeutic Target.

    PubMed

    McCormick, Frank

    2015-04-15

    KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus. PMID:25878360

  11. Antihyperlipidemic therapies targeting PCSK9.

    PubMed

    Weinreich, Michael; Frishman, William H

    2014-01-01

    Hyperlipidemia is a major cause of cardiovascular disease despite the availability of first-line cholesterol-lowering agents such as statins. A new therapeutic approach to lowering low-density lipoprotein-cholesterol (LDL-C) acts by blocking LDL-receptor degradation by serum proprotein convertase subtilisin kexin 9 (PCSK9). Human monoclonal antibodies that target PCSK9 and its interaction with the LDL receptor are now in clinical trials (REGN727/SAR23653, AMG145, and RN316). These agents are administered by either subcutaneous or intravenous routes, and have been shown to have major LDL-C and apolipoprotein B effects when combined with statins. A phase III clinical trial program evaluating clinical endpoints is now in progress. Other PCSK9-targeted approaches are in early stages of investigation, including natural inhibitors of PCSK9, RNA interference, and antisense inhibitors. PMID:24407047

  12. Chloride channels as drug targets

    PubMed Central

    Verkman, Alan S.; Galietta, Luis J. V.

    2013-01-01

    Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets. Chloride channels are involved in a wide range of biological functions, including epithelial fluid secretion, cell-volume regulation, neuroexcitation, smooth-muscle contraction and acidification of intracellular organelles. Mutations in several chloride channels cause human diseases, including cystic fibrosis, macular degeneration, myotonia, kidney stones, renal salt wasting and hyperekplexia. Chloride-channel modulators have potential applications in the treatment of some of these disorders, as well as in secretory diarrhoeas, polycystic kidney disease, osteoporosis and hypertension. Modulators of GABAA (?-aminobutyric acid A) receptor chloride channels are in clinical use and several small-molecule chloride-channel modulators are in preclinical development and clinical trials. Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery. PMID:19153558

  13. Targeting amyloid-? in glaucoma treatment

    PubMed Central

    Guo, Li; Salt, Thomas E.; Luong, Vy; Wood, Nicholas; Cheung, William; Maass, Annelie; Ferrari, Giulio; Russo-Marie, Françoise; Sillito, Adam M.; Cheetham, Michael E.; Moss, Stephen E.; Fitzke, Frederick W.; Cordeiro, M. Francesca

    2007-01-01

    The development of the devastating neurodegenerative condition, Alzheimer's disease, is strongly associated with amyloid-? (A?) deposition, neuronal apoptosis, and cell loss. Here, we provide evidence that implicates these same mechanisms in the retinal disease glaucoma, a major cause of irreversible blindness worldwide, previously associated simply with the effects of intraocular pressure. We show that A? colocalizes with apoptotic retinal ganglion cells (RGC) in experimental glaucoma and induces significant RGC apoptosis in vivo in a dose- and time-dependent manner. We demonstrate that targeting different components of the A? formation and aggregation pathway can effectively reduce glaucomatous RGC apoptosis in vivo, and finally, that combining treatments (triple therapy) is more effective than monotherapy. Our work suggests that targeting the A? pathway provides a therapeutic avenue in glaucoma management. Furthermore, our work demonstrates that the combination of agents affecting multiple stages in the A? pathway may be the most effective strategy in A?-related diseases. PMID:17684098

  14. Multishell inertial confinement fusion target

    DOEpatents

    Holland, James R. (Butler, PA); Del Vecchio, Robert M. (Vandergrift, PA)

    1987-01-01

    A method of fabricating multishell fuel targets for inertial confinement fusion usage. Sacrificial hemispherical molds encapsulate a concentric fuel pellet which is positioned by fiber nets stretched tautly across each hemispherical mold section. The fiber ends of the net protrude outwardly beyond the mold surfaces. The joint between the sacrificial hemispheres is smoothed. A ceramic or glass cover is then deposited about the finished mold surfaces to produce an inner spherical surface having continuously smooth surface configuration. The sacrificial mold is removed by gaseous reactions accomplished through the porous ceramic cover prior to enclosing of the outer sphere by addition of an outer coating. The multishell target comprises the inner fuel pellet concentrically arranged within a surrounding coated cover or shell by fiber nets imbedded within the cover material.

  15. Targeting molecular addictions in cancer.

    PubMed

    Vivanco, I

    2014-11-25

    Cancer cells depend on a finite number of critical signals for their survival. Oncogene addiction, that is, the acquired dependence of a cancer cell on the activity of a single oncogenic gene product, has been the basis for the targeted therapy paradigm, and operationally defines such signals. Additionally, cancer cells have altered metabolic requirements that create addictions to specific nutrients such as glucose and glutamine. In this review, I will discuss the therapeutic opportunities that these two types of molecular addictions offer, focusing on lessons learned from targeting members of the epidermal growth factor receptor family of kinases, and components of MAPK pathway. I will also discuss the challenges in simultaneously harnessing two types of molecular addictions for therapeutic benefit, and the importance of understanding not only the effects of oncogenic signal transduction on metabolism, but also the impact of metabolic states on signal transduction. PMID:25268375

  16. Targeted therapies for bone sarcomas

    PubMed Central

    Heymann, Dominique; Rédini, Françoise

    2013-01-01

    Bone sarcomas include a very large number of tumour subtypes, which originate form bone and more particularly from mesenchymal stem cell lineage. Osteosarcoma, Ewing's sarcoma and chondrosarcoma, the three main bone sarcoma entities develop in a favourable microenvironment composed by bone cells, blood vessels, immune cells, based on the ‘seed and soil theory'. Current therapy associates surgery and chemotherapy, however, bone sarcomas remain diseases with high morbidity and mortality especially in children and adolescents. In the past decade, various new therapeutic approaches emerged and target the tumour niche or/and directly the tumour cells by acting on signalling/metabolic pathways involved in cell proliferation, apoptosis or drug resistance. The present review gives a brief overview from basic to clinical assessment of the main targeted therapies of bone sarcoma cells. PMID:24422100

  17. Jet Perturbation by HE target

    SciTech Connect

    Poulsen, P; Kuklo, R M

    2001-03-01

    We have previously reported the degree of attenuation and perturbation by a Cu jet passing through Comp B explosive. Similar tests have now been performed with high explosive (HE) targets having CJ pressures higher than and lower than the CJ pressure of Comp B. The explosives were LX-14 and TNT, respectively. We found that the measured exit velocity of the jet where it transitions from perturbed to solid did not vary significantly as a function of HE type for each HE thickness. The radial momentum imparted to the perturbed jet segment did vary as a function of HE type, however, and we report the radial spreading of the jet and the penetration of a downstream target as a function of HE type and thickness.

  18. Overview of Solid Target Studies for a Neutrino Factory Neutrino Factory Target Concepts

    E-print Network

    McDonald, Kirk

    expansion of the target material. These shocks can potentially exceed the mechanical strength of solidOverview of Solid Target Studies for a Neutrino Factory Neutrino Factory Target Concepts Parameters of the Neutrino Factory Target Proton Beam pulsed 50 Hz bunches 3 (2 ns rms) energy 10 GeV beam power 4 MW Target

  19. Neurological autoimmunity targeting aquaporin-4

    Microsoft Academic Search

    S. R. Hinson; A. McKeon; V. A. Lennon

    2010-01-01

    Neuromyelitis optica (NMO) is the first inflammatory autoimmune demyelinating disease of the CNS for which a specific tissue target molecule has been identified—the astrocytic water channel aquaporin-4 (AQP4). Immunological insights have propelled significant advances in understanding the clinical, radiologic and immunopathologic characteristics of the disease in the last 5 years. In this review, we describe features distinguishing CNS AQP4 autoimmunity

  20. Targeting TNF-? for cancer therapy

    Microsoft Academic Search

    Elizabeth R Burton; Steven K Libutti

    2009-01-01

    As the tumor vasculature is a key element of the tumor stroma, angiogenesis is the target of many cancer therapies. Recent\\u000a work published in BMC Cell Biology describes a fusion protein that combines a peptide previously shown to home in on the gastric cancer vasculature with the\\u000a anti-tumor cytokine TNF-?, and assesses its potential for gastric cancer therapy.