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Sample records for thrombocytopenic purpura targeting

  1. Thrombotic Thrombocytopenic Purpura

    MedlinePLUS

    ... from the NHLBI on Twitter. What Is Thrombotic Thrombocytopenic Purpura? Thrombotic thrombocytopenic purpura (TTP) is a rare blood ... platelets to form blood clots. Types of Thrombotic Thrombocytopenic Purpura The two main types of TTP are inherited ...

  2. Thrombotic thrombocytopenic purpura

    MedlinePLUS

    Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that causes blood clots to form in small blood vessels. This leads ... McCrae KR, Sadler JE, Cines DB. Thrombotic thrombocytopenic purpura ... HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles ...

  3. Living with Thrombotic Thrombocytopenic Purpura

    MedlinePLUS

    ... from the NHLBI on Twitter. Living With Thrombotic Thrombocytopenic Purpura Some people fully recover from thrombotic thrombocytopenic purpura (TTP). However, relapses (flareups) can occur in many ...

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

    ClinicalTrials.gov

    2016-02-23

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

  5. Drug-induced thrombocytopenic purpura

    PubMed Central

    Sathiasekar, Anisha Cynthia; Deepthi, D. Angeline; Sathia Sekar, G. Suresh

    2015-01-01

    Drug-induced thrombocytopenic purpura is a skin condition result from a low platelet count due to drug-induced anti-platelet antibodies caused by drugs. Drug-induced thrombocytopenic purpura should be suspected when a patient, child or adult, has sudden, severe thrombocytopenia. Drug-induced thrombocytopenic purpura is even more strongly suspected when a patient has repeated episodes of sudden, severe thrombocytopenia PMID:26538982

  6. THROMBOTIC THROMBOCYTOPENIC PURPURA

    PubMed Central

    Bornstein, B.; Boss, J. H.; Casper, J.; Behar, M.

    1960-01-01

    A case of thrombotic thrombocytopenic purpura in a 50-year-old woman is described. Almost the whole course of the disease, lasting 18 months, was characterized by a bizarre neurological disorder, and the haematological manifestations first appeared at a late stage. In many organs a vast number of arterioles and capillaries contained plugs of a fibrinoid material, and fibrinoid was subendothelially accumulated in a few of these vessels; but, in addition, mediumsized arteries of the myocardium were also obstructed by this same material. There were also verrucal endocardiosis of the mitral valve and slight thickening of the glomerular basement membranes. The striking diffusion of a pathological substance through damaged cerebral vessel walls into the nervous tissue seems to be a significant contribution to the understanding of the pathogenesis of the vascular pathology of thrombotic thrombocytopenic purpura. Images PMID:13802905

  7. Idiopathic thrombocytopenic purpura during pregnancy.

    PubMed

    Inocêncio, Gonçalo; Coutinho, Lúcia; Buchner, Graça; Zulmira, Rosa

    2013-01-01

    Idiopathic thrombocytopenic purpura is a very rare disease, especially during pregnancy. It is characterised by low platelet count and predominantly muco-cutaneous bleeding. There are many forms to monitor and treat these patients. Here, we present a case of a pregnant woman, with idiopathic thrombocytopenic purpura, who was submitted to treatment only when the platelet count was below 10,000/?l, with human intravenous immunoglobulin. During the evolution of pregnancy, caesarean delivery and puerperium were favourable. PMID:23307463

  8. Autoimmune thrombocytopenic purpura.

    PubMed

    Karpatkin, S

    1980-09-01

    Adult autoimmune throbocytopenic purpura (ATP) is a platelet disorder that develops in certain individuals with a genetic as well as sex (female) predisposition following an environment event (?viral). This results in the production of an IgG antiplatelet antibody capable of reacting with the host's platelets, as well as crossing the placenta. This leads to the rapid clearance and destruction of opsonized platelets by the reticuloendothelial system, particularly the spleen, by greater than tenfold the normal rate. Bound platelet IgG correlates with disease severity, whereas serum antiplatelet IgG does not. It has not been rigorously established whether bound platelet IgG is directed against a platelet antigen or represents an immune complex bound to the platelet Fc receptor. Nevertheless, several lines of evidence suggest that antiplatelet IgG binds directly to a platelet antigen(s). Megakaryocyte number, volume, and mass are increased commensurate with increased platelet turnover. Platelets of increased size, megathrombocytes, are noted on peripheral smear or via platelet volume distribution analysis. Megathrombocyte number is proporationate to megakarocyte number and to platelet turnover. Megathrombocyte diameter is inversely proportional to platelet survival. Antiplatelet antibody is also associated with qualitative platelet functional defects, which are indistinguishable from those noted with thrombopathia (i.e., apparent platelet release defect). Antibody-induced functional defects are probably more common than quantitative thrombocytopenic defects and may represent a significant portion of those women with the "easy bruising" syndrome and normal platelet count. Adults who develop ATP generally develop the chronic variety, which remains permanently with the patient. Treatment should be directed towards maintaining the patient free of purpura, not restoring the platelet count to normal. This can generally be accomplished with a platelet count of > 40,000/cu mm with patients having this disorder. Approximately 50% of patients respond to steroids by a significant elevation of platelet count and improvement of purpura. However, cessation of therapy results in eventual relapse if the disease is of the chronic variety. Splenectomy is successful in approximately 65-75% of patients, resulting in a restoration of the platelet count to normal or safe levels by removing a major source of platelet destruction as well as antibody production; platelet survival improves. At least 50% of patients "in remission" following steroids or splenectomy generally have a compensated thrombocytolytic state in which increased platelet production keeps up with increased platelet destruction. Antiplatelet IgG can often be found in the serum of these patients. Patients refractory to steroids and/or splenectomy present with a serious therapeutic problem. Immunosuppressive therapy is effective in approximately one-third of refractory patients, but often relapses occur, requiring maintenance therapy with potentially mutagenic drugs... PMID:6157441

  9. Autoimmune thrombocytopenic purpura.

    TOXLINE Toxicology Bibliographic Information

    Karpatkin S

    1980-09-01

    Adult autoimmune throbocytopenic purpura (ATP) is a platelet disorder that develops in certain individuals with a genetic as well as sex (female) predisposition following an environment event (?viral). This results in the production of an IgG antiplatelet antibody capable of reacting with the host's platelets, as well as crossing the placenta. This leads to the rapid clearance and destruction of opsonized platelets by the reticuloendothelial system, particularly the spleen, by greater than tenfold the normal rate. Bound platelet IgG correlates with disease severity, whereas serum antiplatelet IgG does not. It has not been rigorously established whether bound platelet IgG is directed against a platelet antigen or represents an immune complex bound to the platelet Fc receptor. Nevertheless, several lines of evidence suggest that antiplatelet IgG binds directly to a platelet antigen(s). Megakaryocyte number, volume, and mass are increased commensurate with increased platelet turnover. Platelets of increased size, megathrombocytes, are noted on peripheral smear or via platelet volume distribution analysis. Megathrombocyte number is proporationate to megakarocyte number and to platelet turnover. Megathrombocyte diameter is inversely proportional to platelet survival. Antiplatelet antibody is also associated with qualitative platelet functional defects, which are indistinguishable from those noted with thrombopathia (i.e., apparent platelet release defect). Antibody-induced functional defects are probably more common than quantitative thrombocytopenic defects and may represent a significant portion of those women with the "easy bruising" syndrome and normal platelet count. Adults who develop ATP generally develop the chronic variety, which remains permanently with the patient. Treatment should be directed towards maintaining the patient free of purpura, not restoring the platelet count to normal. This can generally be accomplished with a platelet count of > 40,000/cu mm with patients having this disorder. Approximately 50% of patients respond to steroids by a significant elevation of platelet count and improvement of purpura. However, cessation of therapy results in eventual relapse if the disease is of the chronic variety. Splenectomy is successful in approximately 65-75% of patients, resulting in a restoration of the platelet count to normal or safe levels by removing a major source of platelet destruction as well as antibody production; platelet survival improves. At least 50% of patients "in remission" following steroids or splenectomy generally have a compensated thrombocytolytic state in which increased platelet production keeps up with increased platelet destruction. Antiplatelet IgG can often be found in the serum of these patients. Patients refractory to steroids and/or splenectomy present with a serious therapeutic problem. Immunosuppressive therapy is effective in approximately one-third of refractory patients, but often relapses occur, requiring maintenance therapy with potentially mutagenic drugs...

  10. Update on thrombotic thrombocytopenic purpura.

    PubMed

    Osborn, J Dane; Rodgers, George M

    2011-07-01

    Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, which is classically associated with signs and symptoms of fever, thrombocytopenia, neurologic deficits, hemolytic anemia, and renal failure. It is caused by a deficiency of A Disintegrin-like And Metalloprotease with a ThromboSpondin type1 motif 13 (ADAMTS13), which may be an inherited disorder, but more commonly is an acquired disease due to autoantibodies directed against ADAMTS13. Low ADAMTS13 levels result in increased ultra-large von Willebrand factor multimers, which induce platelet adhesion and thrombosis. Plasma exchange therapy is the standard of care, and has greatly reduced morbidity and mortality. A recent TTP case is reviewed, and treatments for recurrent or refractory TTP are summarized. A scoring system using clinical and laboratory parameters to evaluate which suspected TTP patients will benefit from plasma exchange therapy is also discussed. PMID:22402460

  11. Opana(®) ER induced thrombotic thrombocytopenic purpura.

    PubMed

    Kotbi, Nabil; Han, Bernadine; Cheng, Duncan; Odom, Anna E

    2015-01-01

    We present the case of a patient who developed thrombotic thrombocytopenic purpura (TTP) following intravenous injection of Opana(®) ER. TTP reemerged after three months of abstinence with Opana misuse. This case report brings awareness to the possibility of developing TTP in those who misuse Opana, which is a growing concern. PMID:25995651

  12. Opana® ER induced thrombotic thrombocytopenic purpura

    PubMed Central

    Kotbi, Nabil; Han, Bernadine; Cheng, Duncan; Odom, Anna E

    2015-01-01

    We present the case of a patient who developed thrombotic thrombocytopenic purpura (TTP) following intravenous injection of Opana® ER. TTP reemerged after three months of abstinence with Opana misuse. This case report brings awareness to the possibility of developing TTP in those who misuse Opana, which is a growing concern. PMID:25995651

  13. Recurrent thrombocytopenic purpura associated with accessory spleen.

    PubMed Central

    Hann, I M; Wainscoat, J S

    1976-01-01

    In the case of a boy with a relapsed thrombocytopenic purpura removal of a splenunculus, shown by radioisotope scanning, resulted in a partial remission. The significance of the association of relapse in ITP and the presence of splenunculi remains unknown: investigation of similar cases would clarify the matter. Images FIG. 2 FIG. 1 PMID:944023

  14. Management of immune thrombocytopenic purpura: an update.

    PubMed

    Warrier, Rajasekharan; Chauhan, Aman

    2012-01-01

    Rapid strides have been made in the field of hematology, and advances in immune thrombocytopenic purpura (ITP) management are no exception. From idiopathic to immune, the changed nomenclature is itself a testimonial to the growing awareness and improvements in the management of ITP. We discuss the pathophysiology, clinical presentation, and current management of this common pediatric disorder and summarize current guidelines for ITP treatment. PMID:23049459

  15. [Thrombotic thrombocytopenic purpura in a newborn].

    PubMed

    Ghariani, I; Jmili-Braham, N; Azzebi, O; Kortas, M; Veyradier, A; Bakir, L

    2016-01-01

    We report the case of a newborn presenting with hemolytic anemia, thrombocytopenia, hyperbilirubinemia, and renal failure in the first hours of life. An early plasmatherapy was undertaken, with good outcome. The specific von Willebrand factor-cleaving protease activity (ADAMTS 13 for a disintegrin and metalloprotease with thrombospondin type 1 repeats) was found to be low. This is the specific biologic diagnostic element of congenital thrombotic thrombocytopenic purpura (TTP). This disease of constitutional thrombotic microangiopathy is rare. The prognosis, usually life-threatening, was completely transformed given the better understanding of the pathogenesis of the disease and therapeutic progress. PMID:26552625

  16. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    PubMed Central

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting. PMID:26819784

  17. [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

  18. Purpura

    MedlinePLUS

    ... vitamin C deficiency) Steroid use Certain infections Injury Thrombocytopenic purpura may be due to: Drugs that reduce the platelet count Idiopathic thrombocytopenic purpura (ITP) Immune neonatal thrombocytopenia (can occur in infants ...

  19. [Splenic embolization therapy of idiopathic thrombocytopenic purpura].

    PubMed

    Ji, S Q; Huang, Z Y; Qu, G L

    1991-11-01

    21 patients with chronic idiopathic thrombocytopenic purpura (ITP) and 3 patients with Evan's syndrome underwent partial splenic embolization (PSE). 22 patients underwent PSE once, while 2 patients were treated twice, thus a total of 26 procedures were carried out. Follow-up 3 months after embolization was available in all the 24 patients for their response to embolization therapy. 16 patients (67%) achieved complete remission (platelets greater than 100 x 10(9)/L) and 4 (17%) partial remission (platelets greater than 84 x 10(9)/L) after splenic embolization. A total efficacy rate of 83% was observed. This response to embolization after transcatheter vessel occlusion 3 months after is similar to the reported results of splenectomy. Not only may the morbidity and mortality associated with surgical splenectomy be avoided, but also the noninfarcted spleen may continue to provide immunologic functions. The most important experience in this series, however, was the emphasis on partial (60-70%) rather than total splenic arterial embolization. The sequestration site of platelets was associated with the outcome of splenic embolization. More splenic sequestration sites were found in responders, to the therapy. PMID:1815871

  20. 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

  1. Coexisting Situs Inversus Totalis and Immune Thrombocytopenic Purpura.

    PubMed

    Gundogdu, Kemal; Altintoprak, Fatih; Uzunoğlu, Mustafa Yener; Dikicier, Enis; Zengin, İsmail; Yağmurkaya, Orhan

    2016-01-01

    Situs inversus totalis is a rare congenital abnormality with mirror symmetry of mediastinal and abdominal organs. Immune thrombocytopenic purpura is an autoimmune disease with destruction of thrombocytes. This paper is presentation of surgical approach to a case with coexistence of these two conditions. PMID:26981307

  2. Coexisting Situs Inversus Totalis and Immune Thrombocytopenic Purpura

    PubMed Central

    Gundogdu, Kemal; Altintoprak, Fatih; Uzunoğlu, Mustafa Yener; Dikicier, Enis; Zengin, İsmail; Yağmurkaya, Orhan

    2016-01-01

    Situs inversus totalis is a rare congenital abnormality with mirror symmetry of mediastinal and abdominal organs. Immune thrombocytopenic purpura is an autoimmune disease with destruction of thrombocytes. This paper is presentation of surgical approach to a case with coexistence of these two conditions. PMID:26981307

  3. 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

  4. Thrombocytopenic Purpura Associated with Dietary Supplements Containing Citrus Flavonoids.

    PubMed

    Ghali, Alaa; Bourneau-Martin, Delphine; Dopter, Aymeric; Lainé-Cessac, Pascale; Belizna, Cristina; Urbanski, Geoffrey; Lavigne, Christian

    2015-01-01

    We report a case of thrombocytopenic purpura associated with the intake of two dietary supplements containing mainly citrus flavonoids. This is the first case to be notified to the French Agency for Food, Environmental and Occupational Health Safety (ANSES). It addresses the importance of an accurate medication history interview for each patient. PMID:26242500

  5. Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain abnormalities

    SciTech Connect

    D'Aprile, P.; Carella, A.; Pagliarulo, R. ); Farchi, G. )

    1994-01-01

    We report a case of thrombotic thrombocytopenic purpura evaluated by MR, Multiple hyperintense foci on the TS-weighted images, observed principally in the brain stem and in the region of the basal nuclei, and neurologic signs disappeared after 15 days of therapy. 6 refs., 2 figs.

  6. Recent advances in thrombotic thrombocytopenic purpura.

    PubMed

    Sadler, J Evan; Moake, Joel L; Miyata, Toshiyuki; George, James N

    2004-01-01

    Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia and thrombocytopenia, accompanied by microvascular thrombosis that causes variable degrees of tissue ischemia and infarction. Intravascular coagulation is not a prominent feature of the disorder. Plasma exchange can induce remissions in approximately 80% of patients with idiopathic TTP, but patients have a much worse prognosis when thrombotic microangiopathy is associated with cancer, certain drugs, infections, or tissue transplantation. Recently, acquired autoimmune deficiency of a plasma metalloprotease named ADAMTS13 was shown to cause many cases of idiopathic TTP. This review describes our current understanding of how to use this knowledge clinically. In Section I, Dr. Joel Moake describes the presentation of thrombotic microangiopathy, emphasizing the pathophysiology of idiopathic TTP. Platelets adhere to ultra-large (or "unusually large") von Willebrand factor (ULVWF) multimers that are immobilized in exposed subendothelial connective tissue and secreted into the circulation in long "strings" from stimulated endothelial cells. ADAMTS13 cleaves ULVWF multimers within growing platelet aggregates under flowing conditions, and this normally limits platelet thrombus formation. If ADAMTS13 is absent, either congenitally or due to acquired autoantibodies, platelet-rich microvascular thrombosis proceeds unchecked and TTP ensues. Plasma exchange is effective therapy for idiopathic TTP, probably because it replenishes the deficient ADAMTS13 and removes some of the pathogenic autoantibodies and endothelial-stimulating cytokines. Some patients have a type of thrombotic microangiopathy after transplantation/chemotherapy but do not have severe ADAMTS13 deficiency. The pathogenesis of their disease must differ but remains poorly understood. In Section II, Dr. Toshiyuki Miyata describes recent advances in assay methods that should facilitate routine laboratory testing of ADAMTS13 for patients with thrombotic microangiopathy. ADAMTS13 cleaves a single Tyr-Met bond in domain A2 of the VWF subunit. ADAMTS13 assays based on the cleavage of plasma VWF multimers have been used extensively but require considerable time and expertise to perform. A recombinant substrate containing 73 amino acid residues of VWF domain A2 has been devised that allows short incubation times and rapid product detection by gel electrophoresis or immunoassay. These results should encourage the development of even simpler assays that can be performed in most clinical laboratories. In Section III, Dr. James George provides an update on the long-term prospective study of thrombotic microangiopathy in the Oklahoma TTP-HUS Registry. At presentation, the clinical distinction between idiopathic TTP, various forms of secondary thrombotic microangiopathy, and even Shiga toxin-associated hemolytic uremic syndrome (HUS) can be problematic because the symptoms and laboratory findings often overlap. Consequently, plasma exchange usually is administered to any patient with thrombotic microangiopathy if there is doubt about the cause. The role of ADAMTS13 testing in choosing therapy remains uncertain, but the results do appear to have prognostic significance. Severe ADAMTS13 deficiency is specific for idiopathic TTP and identifies a subgroup with a high likelihood of response to plasma exchange, and high-titer ADAMTS13 inhibitors correlate strongly with a high risk of relapsing disease. Patients with normal ADAMTS13 activity have a much worse prognosis, although many factors probably contribute to this difference. Longitudinal study of these patients will continue to clarify the relationship of ADAMTS13 deficiency to the clinical course of thrombotic microangiopathy. PMID:15561695

  7. 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

  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. Accessory spleen compromising response to splenectomy for idiopathic thrombocytopenic purpura

    SciTech Connect

    Ambriz, P.; Munoz, R.; Quintanar, E.; Sigler, L.; Aviles, A.; Pizzuto, J.

    1985-06-01

    Accessory spleens were sought in 28 patients who had undergone splenectomy for chronic idiopathic thrombocytopenic purpura (ITP), using a variety of techniques. Abdominal scintigraphy with autologous erythrocytes labeled with Tc-99m and opsonized with anit-D IgG (radioimmune method) proved to be most useful, clearly demonstrating one or more accessory spleens in 12 cases (43%). Computed tomography (CT) was also helpful. Four out of five patients demonstrated an increased platelet count following surgery, the effectiveness of which was illustrated by the radioimmune scan. Patients who have had splenectomy for chronic ITP should be scanned using radioimmune techniques and CT to determine whether an accessory spleen is present.

  10. Intrahepatic splenosis after splenectomy performed for idiopathic thrombocytopenic purpura

    PubMed Central

    Tokta?, Osman; Yavuz, Alpaslan; ?liklerden, Ümit; Y?lmaz, Deniz; Bayram, ?rfan

    2015-01-01

    The term splenosis describes autotransplantation or implantation of ectopic splenic tissue within the abdominal cavity or in any other unusual body compartment. In addition to the diagnostic dilemma it causes, splenosis may also lead to persistence or recurrence of hematologic dysfunctions by its preserved immune activity especially in cases of splenectomy due to hematologic indications. Herein, we present a 40-year-old female who had splenectomy for idiopatic thrombocytopenic purpura, and was identified to have splenic tissue within left lobe of the liver during further assessment of ongoing thrombocytopenia.

  11. Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome and pregnancy

    PubMed Central

    Mwita, Julius Chacha; Vento, Sandro; Benti, Tadele

    2014-01-01

    Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome (TTP-HUS) is a rare pregnancy and postpartum complication that may simulate the more common obstetric complications, preeclampsia and the syndrome of haemolysis, elevated liver functions tests, low platelets (HELLP). We describe a 26 years old patient who presented with peri-partum TTP-HUSand was initially treated as a case of HELLP syndrome without any improvement. A brief review of the current TTP-HUS treatment options in pregnancy is also presented. PMID:25309655

  12. A Case of Immune Thrombocytopenic Purpura After Rabies Vaccination.

    PubMed

    Fulbright, Joy M; Williams, Sarah E; Pahud, Barbara A

    2015-10-01

    We describe a case of immune thrombocytopenic purpura (ITP) occurring 15 days after the first dose of a 4-dose rabies vaccination series. ITP is thought to be an immune-mediated process triggered by an infection or toxin. There is little evidence in the literature beyond case reports of an association of ITP with vaccines other than with the measles, mumps, and rubella vaccine. This is the third reported case of ITP associated with rabies vaccination. Because of the rare occurrence of this adverse event relative to the severity of rabies infection, the benefits of rabies vaccination, when indicated, outweigh the low and possible risk of ITP. PMID:26165405

  13. A report of disseminated adenocarcinoma presenting as thrombotic thrombocytopenic purpura

    PubMed Central

    Alonso, Joaquín Valle; Fonseca, Javier; Lopera, Elisa Lopera; Aguayo, Miguel Ángel; Montes, Yelda Hernandez; Llamas, Jose Carlos

    2011-01-01

    Thrombotic microangiopathies (TMAs) represent a heterogeneous group of diseases characterized by a microangiopathic hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. TMAs encompass thrombotic thrombocytopenic purpura (TTP), typically characterized by fever, central nervous system manifestations and hemolytic uremic syndrome (HUS), in which renal failure is the prominent abnormality. In patients with cancer TMAs may be related to various antineoplastic drugs or to the malignant disease itself. The reported series of patients with TMAs directly related to cancer are usually heterogeneous, retrospective, and encompass patients with hematologic malignancies with solid tumors or receiving chemotherapy, each of which may have distinct presentations and pathophysiological mechanisms. Patients with disseminated malignancy who present with microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as thrombotic thrombocytopenic purpura (TTP) Only a few cases of TTP secondary to metastatic adenocarcinoma are known in the literature. We present a case of a 34-year-old man with TTP syndrome secondary to metastatic small-bowel adenocarcinoma. Patients with disseminated malignancy had a longer duration of symptoms, more frequent presence of respiratory symptoms, higher lactate dehydrogenase levels, and more often failed to respond to plasma exchange treatment. A search for systemic malignancy, including a bone marrow biopsy, is appropriate when patients with TTP have atypical clinical features or fail to respond to plasma exchange. PMID:22184535

  14. A report of disseminated adenocarcinoma presenting as thrombotic thrombocytopenic purpura.

    PubMed

    Alonso, Joaquín Valle; Fonseca, Javier; Lopera, Elisa Lopera; Aguayo, Miguel Ángel; Montes, Yelda Hernandez; Llamas, Jose Carlos

    2011-08-31

    Thrombotic microangiopathies (TMAs) represent a heterogeneous group of diseases characterized by a microangiopathic hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. TMAs encompass thrombotic thrombocytopenic purpura (TTP), typically characterized by fever, central nervous system manifestations and hemolytic uremic syndrome (HUS), in which renal failure is the prominent abnormality. In patients with cancer TMAs may be related to various antineoplastic drugs or to the malignant disease itself. The reported series of patients with TMAs directly related to cancer are usually heterogeneous, retrospective, and encompass patients with hematologic malignancies with solid tumors or receiving chemotherapy, each of which may have distinct presentations and pathophysiological mechanisms. Patients with disseminated malignancy who present with microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as thrombotic thrombocytopenic purpura (TTP) Only a few cases of TTP secondary to metastatic adenocarcinoma are known in the literature. We present a case of a 34-year-old man with TTP syndrome secondary to metastatic small-bowel adenocarcinoma. Patients with disseminated malignancy had a longer duration of symptoms, more frequent presence of respiratory symptoms, higher lactate dehydrogenase levels, and more often failed to respond to plasma exchange treatment. A search for systemic malignancy, including a bone marrow biopsy, is appropriate when patients with TTP have atypical clinical features or fail to respond to plasma exchange. PMID:22184535

  15. Treatment of Congenital Thrombotic Thrombocytopenic Purpura With Eculizumab.

    PubMed

    Pecoraro, Carmine; Ferretti, Alfonso Vincenzo Salvatore; Rurali, Erica; Galbusera, Miriam; Noris, Marina; Remuzzi, Giuseppe

    2015-12-01

    A 12-year-old boy was hospitalized for hemolytic anemia, thrombocytopenia, acute kidney injury, and generalized seizures. The childhood onset, severely decreased kidney function, absence of prodromal diarrhea, negative test results for Shiga-like toxin-producing Escherichia coli, elevated plasma levels of the terminal complement complex sC5b-9, and ex vivo testing in endothelial cells showing serum-induced complement activation were all consistent with a diagnosis of complement-mediated atypical hemolytic uremic syndrome. Before plasma ADAMTS13 (von Willebrand factor protease) activity results were available, the patient was treated with the anti-C5 monoclonal antibody eculizumab, and treatment was followed by prompt disease remission. However, results of ADAMT13 activity level tests and gene screening revealed a severe deficiency associated with 2 heterozygous mutations in the ADAMTS13 gene, fully consistent with a diagnosis of congenital thrombotic thrombocytopenic purpura. Screening for atypical hemolytic uremic syndrome-associated genes failed to show a mutation and an assay for plasma anti-factor H antibodies gave negative results both before and after eculizumab treatment initiation. The patient's clinical evolution suggests that complement activation plays a role in the pathogenesis of thrombotic thrombocytopenic purpura and provides unexpected new insights into the treatment of this life-threatening disease. PMID:26409664

  16. Immune Thrombocytopenic Purpura Secondary to Cytomegalovirus Infection: A Case Report

    PubMed Central

    Flores-Chang, Bessy S.; Arias-Morales, Carlos E.; Wadskier, Francis G.; Gupta, Sorab; Stoicea, Nicoleta

    2015-01-01

    Immune thrombocytopenic purpura (ITP) is defined as an acquired thrombocytopenia with antibodies detected against platelet surface antigens, and it is the most common form of thrombocytopenia in otherwise asymptomatic adults. ITP secondary to an underlying condition is a diagnosis of exclusion that is essential to establish for treatment efficacy. Secondary thrombocytopenia caused by cytomegalovirus (CMV) is common; however, case reports associated with diagnosis in immunocompetent adults are rare, and to the best of our knowledge only 20 publications have been associated with this diagnosis. Our report is based on a clinical presentation of a 37-year-old female complaining of petechiae, heavy menses, shortness of breath, and a platelet count of 1?×?109/L. Treatment with IVIG and steroids failed to improve platelet count. Subsequently, an infectious laboratory workup was performed, detecting CMV infection, and treatment with antiviral agents was initiated, causing platelet count to increase as viral load decreased. PMID:26579523

  17. Thrombotic Thrombocytopenic Purpura: Three Peripartum Cases and Diagnostic Challenges

    PubMed Central

    Ab Rahman, Wan Suriana Wan; Abdullah, Wan Zaidah; Mustaffa, Rapiaah; Ahmed, Suhair Abbas; Hassan, Mohd Nazri; Husin, Azlan

    2013-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a medical emergency characterized by occlusive microangiopathy due to intravascular platelet aggregation. This event results in damage to the red blood cells (RBCs) known as microangiopathic hemolytic anemia (MAHA). Schistocytes are circulating fragments of damaged RBCs that have different morphological features including keratocytes, helmet cells, and spherocytes. It is critical to report even a small number of these abnormal RBCs in the peripheral blood and to be alert for the possible diagnosis of TTP, especially in unexplained anemia and thrombocytopenia. The application of pentad criteria in the diagnosis has been reviewed, and the challenges still remained on the hematologic evidence of this disorder. In the 3 cases discussed here, the red cell morphological diagnosis gave an impact on TTP diagnosis, but overdiagnosis might be encountered in obstetrical patients due to nonspecific diagnostic criteria. PMID:24093001

  18. Thrombotic thrombocytopenic purpura: three peripartum cases and diagnostic challenges.

    PubMed

    Ab Rahman, Wan Suriana Wan; Abdullah, Wan Zaidah; Mustaffa, Rapiaah; Ahmed, Suhair Abbas; Hassan, Mohd Nazri; Husin, Azlan

    2013-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a medical emergency characterized by occlusive microangiopathy due to intravascular platelet aggregation. This event results in damage to the red blood cells (RBCs) known as microangiopathic hemolytic anemia (MAHA). Schistocytes are circulating fragments of damaged RBCs that have different morphological features including keratocytes, helmet cells, and spherocytes. It is critical to report even a small number of these abnormal RBCs in the peripheral blood and to be alert for the possible diagnosis of TTP, especially in unexplained anemia and thrombocytopenia. The application of pentad criteria in the diagnosis has been reviewed, and the challenges still remained on the hematologic evidence of this disorder. In the 3 cases discussed here, the red cell morphological diagnosis gave an impact on TTP diagnosis, but overdiagnosis might be encountered in obstetrical patients due to nonspecific diagnostic criteria. PMID:24093001

  19. Postinfluenza Vaccination Idiopathic Thrombocytopenic Purpura in Three Elderly Patients.

    PubMed

    Nagasaki, Joji; Manabe, Masahiro; Ido, Kentaro; Ichihara, Hiroyoshi; Aoyama, Yasutaka; Ohta, Tadanobu; Furukawa, Yoshio; Mugitani, Atsuko

    2016-01-01

    The etiologies of secondary idiopathic thrombocytopenic purpura (ITP) include infection, autoimmune disease, and immunodeficiency. We report the cases of three elderly patients who developed ITP after receiving influenza vaccinations. The platelet count of an 81-year-old woman fell to 27,000/μL after she received an influenza vaccination. A 75-year-old woman developed thrombocytopenia (5,000 platelets/μL) after receiving an influenza vaccination. An 87-year-old woman whose laboratory test values included a platelet count of 2,000/μL experienced genital bleeding after receiving an influenza vaccination. After Helicobacter pylori (HP) eradication or corticosteroid treatment, all of the patients' platelet counts increased. Influenza vaccination is an underlying etiology of ITP in elderly patients. HP eradication or corticosteroid treatment is effective for these patients. Clinicians should be aware of the association between ITP and influenza vaccinations. PMID:26998369

  20. Postinfluenza Vaccination Idiopathic Thrombocytopenic Purpura in Three Elderly Patients

    PubMed Central

    Nagasaki, Joji; Manabe, Masahiro; Ido, Kentaro; Ichihara, Hiroyoshi; Aoyama, Yasutaka; Ohta, Tadanobu; Furukawa, Yoshio; Mugitani, Atsuko

    2016-01-01

    The etiologies of secondary idiopathic thrombocytopenic purpura (ITP) include infection, autoimmune disease, and immunodeficiency. We report the cases of three elderly patients who developed ITP after receiving influenza vaccinations. The platelet count of an 81-year-old woman fell to 27,000/μL after she received an influenza vaccination. A 75-year-old woman developed thrombocytopenia (5,000 platelets/μL) after receiving an influenza vaccination. An 87-year-old woman whose laboratory test values included a platelet count of 2,000/μL experienced genital bleeding after receiving an influenza vaccination. After Helicobacter pylori (HP) eradication or corticosteroid treatment, all of the patients' platelet counts increased. Influenza vaccination is an underlying etiology of ITP in elderly patients. HP eradication or corticosteroid treatment is effective for these patients. Clinicians should be aware of the association between ITP and influenza vaccinations. PMID:26998369

  1. Mechanisms of intravenous immunoglobulin action in immune thrombocytopenic purpura.

    PubMed

    Jin, Feng; Balthasar, Joseph P

    2005-04-01

    The use of high-dose intravenous gamma immunoglobulin (IVIG) for the treatment of immune thrombocytopenic purpura (ITP) was first reported more than two decades ago. After the therapeutic benefit of IVIG was established in ITP, it was then successfully used to treat many other autoimmune diseases. Although a complete definition of the mechanism of IVIG action is still lacking, extensive research suggests that IVIG may achieve its therapeutic effects through multiple mechanisms. IVIG exerts immunomodulatory effects that may include antiidiotypic neutralization of antiplatelet antibodies, stimulation of Fcgamma receptor IIB expression, and inhibition of Fcgamma receptor-mediated platelet destruction. Recent work suggests that a large fraction of the benefit provided by IVIG may be the result of competitive inhibition of neonatal Fc receptor (FcRn) and IVIG-induced acceleration of antiplatelet antibody elimination. This review provides an overview and critical discussion of mechanisms that may be responsible of IVIG effects in ITP. PMID:15866704

  2. Dengue Virus Infection Triggering Thrombotic Thrombocytopenic Purpura in Pregnancy.

    PubMed

    Deepanjali, Surendran; Naik, Raghuramulu R; Mailankody, Sharada; Kalaimani, Sivamani; Kadhiravan, Tamilarasu

    2015-11-01

    We report a case of thrombotic thrombocytopenic purpura (TTP) that immediately followed symptomatic dengue virus infection in a pregnant lady. The patient developed dengue fever at 16 weeks of gestation, resulting in spontaneous abortion. Subsequently, fever reappeared with persistent thrombocytopenia and jaundice. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. The TTP episode resolved after six cycles of therapeutic plasma exchange with fresh-frozen plasma. An ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13 repeats) activity assay, done during convalescence, showed normal activity. The patient had an uneventful second pregnancy and has remained free of TTP recurrence for more than 2 years now. We review the pathophysiological basis of TTP in dengue infection, and suggest that jaundice with disproportionate elevation of serum aspartate aminotransferase level in a patient with dengue should arouse the suspicion of TTP. PMID:26283741

  3. ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

    PubMed Central

    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

  4. Disordered immune homeostasis in chronic idiopathic thrombocytopenic purpura.

    PubMed Central

    Trent, R J; Clancy, R L; Danis, V; Basten, A

    1981-01-01

    A T:B co-culture system was used to test for the presence of disordered immune homeostasis in the autoimmune disease, chronic idiopathic thrombocytopenic purpura (ITP). Various numbers of T cells were added to a fixed number of B cells in the presence or absence of the polyclonal activator, pokeweed mitogen, and IgG production measured in the culture supernatants 6 days later. The results demonstrated a defect in T cell-dependent suppression and/or a state of B cell hyper-responsiveness in lymphocytes from patients compared to normal controls. The loss of T cell-dependent suppression could not be readily explained in terms of the therapy being used nor by the presence of circulating IgG containing immune complexes. The findings of a similar abnormality in some cases of non-immune thrombocytopenia suggested that the reduction in suppression observed in chronic ITP was unlikely to be a primary event in disease pathogenesis, although it could well contribute to the ongoing autoimmune response. PMID:6975684

  5. Thrombotic thrombocytopenic purpura: survival by "giving a dam".

    PubMed Central

    Moake, Joel L.

    2004-01-01

    A teenager died suddenly in 1923 of systemic microvascular thrombosis. Dr. Eli Moschcowitz attributed the "hitherto undescribed disease" (now "thrombotic thrombocytopenic purpura," or "TTP") to "some powerful poison" with "both agglutinative and hemolytic properties." In 1982, TTP was found to be a defect in the "processing" of unusually large (UL) von Willebrand factor (VWF) multimers. By 1998, the cause of TTP was known to be either familial absence or acquired inhibition (by autoantibody) of plasma VWF-cleaving metalloprotease. This enzyme, the 13th member of a disintegrin and metalloprotease family with thrombospondin domains (ADAMTS-13), circulates in normal plasma waiting to cleave the long strings of ULVWF multimers emerging from stimulated endothelial cells. Uncleaved ULVWF multimers in TTP induce platelet adhesion and aggregation in the rapidly flowing blood of microvessels. Episodes of TTP are treated by "giving A DAM" (TS-13, that is) contained in normal plasma, either by infusion alone or in combination with plasmapheresis. Images Fig. 1 Fig. 2 Fig. 5 PMID:17060968

  6. Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

    SciTech Connect

    Ware, R.; Kinney, T.R.; Rosse, W.

    1985-11-01

    Evaluations were performed in 20 patients with childhood idiopathic thrombocytopenic purpura (ITP) who remained in remission longer than 12 months. The mean duration of follow-up from diagnosis was 39 months (range 17 to 87 months). Eleven patients (four girls) in group 1 had an acute course of ITP, defined as platelet count greater than 150 X 10(9)/L within 6 months of diagnosis. Nine patients (five girls) in group 2 had a chronic course, defined as platelet count less than 150 X 10(9)/L for greater than or equal to 1 year or requiring splenectomy in an attempt to control hemorrhagic symptoms. Platelet count and serum (indirect) platelet-associated IgG (PAIgG) levels were normal in all 20 patients at follow-up. Both direct and indirect PAIgG levels were measured using a SVI-monoclonal anti-IgG antiglobulin assay. All had normal direct PAIgG levels, except for one patient in group 1 who had a borderline elevated value of 1209 molecules per platelet. These data suggest that the prevalence of elevated platelet antibodies is low during sustained remission without medication in patients with a history of childhood ITP. These data may be relevant for pregnant women with a history of childhood ITP, with regard to the risk of delivering an infant with thrombocytopenia secondary to transplacental passage of maternal platelet antibody.

  7. 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.

  8. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy

    PubMed Central

    Blum, Daniel; Blake, Geoffrey

    2015-01-01

    Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady’s TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID:26558190

  9. Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange.

    PubMed

    Coppo, Paul; Froissart, Antoine

    2015-12-01

    Daily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of 80%-85%. However, relapses occur in ?40% of patients and refractory disease with fatal outcomes still occurs. In this context, the introduction of rituximab has probably been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, or even as frontline therapy, with high response rates. In more severe patients, salvage strategies may include twice-daily TPE, pulses of cyclophosphamide, vincristine, as well as splenectomy in more desperate cases. In this life-threatening disease, relapse prevention represents a major goal. Persistent severe acquired ADAMTS13 deficiency in patients who are otherwise in remission is associated with a high risk of relapse and preemptive treatment with rituximab may be considered in this context. In the coming years, the TTP therapeutic landscape should be enriched by original strategies stemming from clinical experience and new agents that are currently being evaluated in large, ideally international, clinical trials. Promising agents under evaluation include N-acetylcysteine, bortezomib, recombinant ADAMTS13, and inhibitors of the glycoprotein-Ib/IX-von Willebrand factor axis. PMID:26637782

  10. Changes in splenic microcirculatory pathways in chronic idiopathic thrombocytopenic purpura.

    PubMed

    Schmidt, E E; MacDonald, I C; Groom, A C

    1991-09-15

    The spleen plays a central role in the pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP); it produces massive quantities of antiplatelet antibodies, leading to accelerated phagocytosis of platelets. Lymphoid hyperplasia typically occurs in the spleen, characterized by large numbers of lymphatic nodules with active germinal centers. Whether changes in splenic microcirculatory pathways also occur is not known. We have studied this question by scanning electron microscopy of corrosion casts, comparing spleens removed from patients with ITP with normal spleens obtained from organ transplant donors. The casts demonstrate two major changes in microcirculatory pathways in ITP. Firstly, a striking proliferation of arterioles and capillaries is found in the white pulp and marginal zone (MZ), seen as extensive vascularization in 92.3% of lymphatic nodules (n = 191) versus 0.6% (n = 224) in normal spleens. Secondly, the marginal sinus, a series of flattened, anastomosing vascular spaces between the white pulp and MZ, is absent in 89.4% of lymphatic nodules versus 4.9% in normal spleens. The cause of these microcirculatory changes, which may not be exclusive to ITP, is presently unknown. Absence of the marginal sinus may affect distribution of blood flow through the MZ such that platelets spend increased amounts of time in the proximity of macrophages. In the presence of antiplatelet antibodies found in ITP spleens, this delayed transit would lead to greatly increased platelet destruction. PMID:1884017

  11. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy.

    PubMed

    Blum, Daniel; Blake, Geoffrey

    2015-11-01

    Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady's TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID:26558190

  12. Evaluation and management of patients with thrombotic thrombocytopenic purpura.

    PubMed

    George, James N

    2007-01-01

    Thrombotic thrombocytopenic purpura (TTP) describes syndromes with multiple etiologies, some of which are rapidly fatal without plasma exchange treatment. Although there have been advances in understanding the pathogenesis of TTP, evaluation and management remain difficult because there are no specific diagnostic criteria, as TTP can be clinically similar to other acute disorders, such as sepsis, disseminated malignancy, malignant hypertension, and preeclampsia, and because urgent treatment is required. An unexpected observation of anemia and thrombocytopenia should trigger consideration of TTP; evidence that the anemia is due to microangiopathic hemolysis, suggested by the presence of red cell fragmentation on the blood smear, supports the diagnosis. When the diagnostic criteria of microangiopathic hemolytic anemia and thrombocytopenia without an apparent alternative etiology are fulfilled, plasma exchange treatment is appropriate. However, plasma exchange has risks for severe complications and death; therefore, this management decision must be balanced against the confidence in the diagnosis. With plasma exchange treatment, approximately 80% of patients survive, in contrast to only 10% in the era prior to the availability of plasma exchange. The continuing mortality from TTP, the risks of plasma exchange treatment, and the potential for recurrent episodes of TTP are clinical challenges that remain to be solved. PMID:17456728

  13. Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura

    PubMed Central

    Jiang, Yang; McIntosh, Jennifer J.; Reese, Jessica A.; Deford, Cassandra C.; Kremer Hovinga, Johanna A.; Lämmle, Bernhard; Terrell, Deirdra R.; Vesely, Sara K.; Knudtson, Eric J.

    2014-01-01

    Pregnancy may precipitate acute episodes of thrombotic thrombocytopenic purpura (TTP), but pregnancy outcomes in women who have recovered from acquired TTP are not well documented. We analyzed pregnancy outcomes following recovery from TTP associated with acquired, severe ADAMTS13 deficiency (ADAMTS13 activity <10%) in women enrolled in the Oklahoma TTP-HUS Registry from 1995 to 2012. We also systematically searched for published reports on outcomes of pregnancies following recovery from TTP associated with acquired, severe ADAMTS13 deficiency. Ten women in the Oklahoma Registry had 16 subsequent pregnancies from 1999 to 2013. Two women had recurrent TTP, which occurred 9 and 29 days postpartum. Five of 16 pregnancies (31%, 95% confidence interval, 11%-59%) in 3 women were complicated by preeclampsia, a frequency greater than US population estimates (2.1%-3.2%). Thirteen (81%) pregnancies resulted in normal children. The literature search identified 382 articles. Only 6 articles reported pregnancies in women who had recovered from TTP associated with acquired, severe ADAMTS13 deficiency, describing 10 pregnancies in 8 women. TTP recurred in 6 pregnancies. Conclusions: With prospective complete follow-up, recurrent TTP complicating subsequent pregnancies in Oklahoma patients is uncommon, but the occurrence of preeclampsia may be increased. Most pregnancies following recovery from TTP in Oklahoma patients result in normal children. PMID:24398329

  14. Platelet-associated CD154 in immune thrombocytopenic purpura.

    PubMed

    Solanilla, Anne; Pasquet, Jean-Max; Viallard, Jean-François; Contin, Cécile; Grosset, Christophe; Déchanet-Merville, Julie; Dupouy, Maryse; Landry, Marc; Belloc, Francis; Nurden, Paquita; Blanco, Patrick; Moreau, Jean-François; Pellegrin, Jean-Luc; Nurden, Alan T; Ripoche, Jean

    2005-01-01

    CD40-ligand (CD154) is expressed on activated CD4+ T lymphocytes and is essential for the T cell-dependent activation of B lymphocytes. CD154 is also expressed at the activated platelet surface. In this study, we show that platelet-associated CD154 is increased in immune thrombocytopenic purpura (ITP), a disease characterized by an autoimmune response against proteins of the platelet membrane. CD154 and its messenger RNA were also present in increased amounts in the megakaryocytes of patients with ITP. We found that platelet-associated CD154 is competent to induce the CD40-dependent proliferation of B lymphocytes, and we observed an in vitro CD154-dependent production of antibodies to the GPIIb/IIIa complex (integrin alphaIIbbeta3) when platelets and peripheral blood B lymphocytes from ITP patients with circulating anti-GPIIb/IIIa antibody were cultured together. Therefore, platelet-associated CD154 expression is increased in ITP and is able to drive the activation of autoreactive B lymphocytes in this disease. PMID:15191945

  15. Left Ventricular Perforation during Catheter Ablation in a Patient with Idiopathic Thrombocytopenic Purpura.

    PubMed

    Sakamoto, Hiroaki; Tsukada, Toru; Tokunaga, Chiho; Matsubara, Muneaki; Aikawa, Shizu; Enomoto, Yoshiharu; Sato, Fujio; Hiramatsu, Yuji

    2015-01-01

    Preoperative gamma-globulin therapy was recently performed to prevent bleeding complications in a patient with concomitant idiopathic thrombocytopenic purpura undergoing cardiac surgery. Here we report the case of a 75-year-old male patient with idiopathic thrombocytopenic purpura, chronic aortic dissection, and funnel chest in whom a left ventricular perforation sustained during catheter ablation was repaired during emergent surgery. Despite preoperative gamma-globulin therapy not being performed, bleeding complications were prevented because platelets were preserved by avoidance of cardiopulmonary bypass use. Although the funnel chest made it difficult to secure the operative field, the deep pericardial sutures were effective in repairing the perforation without cardiopulmonary bypass. PMID:26726712

  16. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura.

    PubMed

    Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

    2015-10-01

    Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64-15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59-27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications. PMID:26496263

  17. Platelet-associated complement C3 in immune thrombocytopenic purpura

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.

    1982-05-01

    Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associatd IgG (PA-lgG) levels were also measured with our standard quantitative immunofluorescence assay. All patients with nonimmune thrombocytopenias and ITP in remission had normal PA-C3 levels. Twenty-four patients with active ITP wre classified into 3 groups: 9 (38%) with increased PA-IgG and normal PA-C3 levels, 10 (42%) with elevated PA-C3 and PA-IgG levels, and 5 (20%) with increased PA-C3 values only. A direct correlation was found between PA-C3 and PA-IgG levels. PA-IgG levels were higher in the group of patients with elevated PA-C3 levels than in those with normal values. Platelet survival studies showed reduced survival times of 1.5-2.5 days for the 5 patients with elevated PA-C3 levels only. Elevated PA-C3 levels returned to normal in 7 ITP patients whose platelet counts increased in response to corticosteriod therapy or to splenectomy. Therefore, PA-C3 and PA-IgG assays can be used to identify patients with ITP, to follow their response to therapy, and to classify them into immunologic subgroups similar to red cell classifiation by Coombs' testing in immune hemolytic anemia.

  18. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

    2015-01-01

    Abstract Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64–15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59–27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications. PMID:26496263

  19. Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura

    PubMed Central

    Noonavath, Ravinder Naik; Lakshmi, Chandrasekharan Padma; Dutta, Tarun Kumar; Kate, Vikram

    2014-01-01

    AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on platelet counts in patients with chronic immune thrombocytopenic purpura (cITP). METHODS: A total of 36 cITP patients were included in the study. The diagnosis of H. pylori was done by rapid urease test and Giemsa staining of the gastric biopsy specimen. All H. pylori positive patients received standard triple therapy for 14 d and were subjected for repeat endoscopy at 6 wk. Patients who continued to be positive for H. pylori on second endoscopy received second line salvage therapy. All the patients were assessed for platelet response at 6 wk, 3rd and 6th months. RESULTS: Of the 36 patients, 17 were positive for H. pylori infection and eradication was achieved in 16 patients. The mean baseline platelet count in the eradicated patients was 88615.38 ± 30117.93/mm3 and platelet count after eradication at 6 wk, 3 mo and 6 mo was 143230.77 ± 52437.51/mm3 (P = 0.003), 152562.50 ± 52892.3/mm3 (P = 0.0001), 150187.50 ± 41796.68/mm3 (P = 0.0001) respectively and in the negative patients, the mean baseline count was 71000.00 ± 33216.46/mm3 and at 6 wk, 3rd and 6th month follow up was 137631.58 ± 74364.13/mm3 (P = 0.001), 125578.95 ± 71472.1/mm3 (P = 0.005), 77210.53 ± 56892.28/mm3 (P = 0.684) respectively. CONCLUSION: Eradication of H. pylori leads to increase in platelet counts in patients with cITP and can be recommended as a complementary treatment with conventional therapy. PMID:24944483

  20. Late Results After Splenectomy in Adult Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Vecchio, Rosario; La Corte, Francesco; Marchese, Salvatore; Cacciola, Rossella R.; Cacciola, Emma

    2015-01-01

    Background: We performed a retrospective study on patients with idiopathic thrombocytopenic purpura (ITP) to evaluate the response to splenectomy in relation to preoperative platelet count. Materials and Methods: Two groups of patients operated on with laparoscopic or open splenectomy for ITP, with a platelet count ?30,000/?L (study group: 22 patients) and >30,000/?L (control group: 18 patients), respectively, were compared. The two groups were homogeneous in relation to age, sex, length of preoperative steroid therapy, and time interval between diagnosis and surgery (Student t test with P > .1). The results of surgery were evaluated at one year after splenectomy. Positive response to surgery, according to the American Society of Hematologic Guidelines, was considered in patients with a postoperative platelet count ?100,000/?L or in patients with a postoperative platelet count ?30,000/?L and a twofold increase in platelet count from baseline, in the absence of bleeding. The postoperative platelet count increase rate was statistically related to preoperative platelet count in both the study and control groups. Statistical analysis was performed using the Student's t test for independent sample and the Pearson correlation in a 2-tailed test. Results: No relationship between preoperative platelet count and postoperative platelet percent increase was observed in the control group (r = –0.41; P = .089), whereas a significant negative correlation (r = –0.68; P = .0004) was found in the study group. Conclusions: A higher increase of postoperative percent platelet count may be predicted in patients with a low preoperative platelet count. PMID:25848175

  1. 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

  2. Thrombotic thrombocytopenic purpura or immune thrombocytopenia in a sickle cell/?+-thalassemia patient: a rare and challenging condition.

    PubMed

    Vlachaki, Efthymia; Agapidou, Aleka; Neokleous, Nikolaos; Adamidou, Despoina; Vetsiou, Evaggelia; Boura, Panagiota

    2014-10-01

    The diagnosis of thrombotic thrombocytopenic purpura is one of the possible diagnosis when a patient is admitted with unexpected micro-angiopathic hemolytic anemia and thrombocytopenia. The combination of sickle cell/?(+)-thalassemia and thrombotic thrombocytopenic purpura is rare and triggering. This article describes the poor outcome of a patient with sickle cell/?(+)-thalassemia presenting with gingival bleeding, severe thrombocytopenia and anemia. The patient had normal renal function, no neurological deficit and he was initially treated as immune thrombocytopenic purpura. He eventually died due to multi-organ failure and brain hemorrhage even though he had started plasma exchange sessions. The co-existence of thrombotic thrombocytopenic purpura and sickle cell anemia is making the diagnosis of the former difficult. Early and rapid intervention is critical to the outcome. PMID:25266987

  3. Resection of bulky chromophobe renal cell carcinoma resolved severe idiopathic thrombocytopenic purpura: A case report.

    PubMed

    Maekawa, Shigekatsu; Nagata, Masayoshi; Watanabe, Hiroshi; Nozaki, Keina; Takahashi, Atsuko; Minowada, Shigeru; Homma, Yukio

    2015-12-01

    Idiopathic thrombocytopenic purpura associated with renal cell carcinoma is relatively rare. We report the case of a 48-year-old woman with massive renal cell carcinoma, measuring approximately 20 × 14 × 14 cm, who presented with severe thrombocytopenia: platelet count, 2000 cells/?L. After confirming normal bone marrow, she received high-dose dexamethasone and intravenous gamma globulin, which raised the platelet count to normal levels. She then underwent left radical nephrectomy. The pathological examination showed chromophobe renal cell carcinoma. After the resection, the platelet count was maintained within the normal range without any treatment. The current case is the first report of chromophobe renal cell carcinoma causative of severe idiopathic thrombocytopenic purpura. PMID:26354444

  4. Thrombotic thrombocytopenic purpura and focal segmental glomerulosclerosis associated with the use of ecstasy

    PubMed Central

    Kayar, Yusuf; Kayar, Nuket Bayram; Gangarapu, Venkatanarayana

    2015-01-01

    Ecstasy is a drug, which causes serious side effects and sometimes it can be lethal. These effects are due to idiosyncratic reactions as a result of various stimulations in adrenergic receptors. Here we present a case of a 36-year-old male patient who was diagnosed with thrombotic thrombocytopenic purpura associated with the use of ecstasy. Plasmapheresis along with methylprednisolone treatment restores patient condition to normal. PMID:25878432

  5. Presumptive thrombotic thrombocytopenic purpura following a hump-nosed viper (Hypnale hypnale) bite: a case report

    PubMed Central

    2014-01-01

    Hump-nosed viper bites are frequent in southern India and Sri Lanka. However, the published literature on this snakebite is limited and its venom composition is not well characterized. In this case, we report a patient with thrombotic thrombocytopenic purpura-like syndrome following envenoming which, to the best of our knowledge, has not been reported in the literature before. A 55-year-old woman from southern Sri Lanka presented to the local hospital 12 hours after a hump-nosed viper (Hypnale hypnale) bite. Five days later, she developed a syndrome that was characteristic of thrombotic thrombocytopenic purpura with fever, thrombocytopenia, microangiopathic hemolysis, renal impairment and neurological dysfunction in the form of confusion and coma. Her clinical syndrome and relevant laboratory parameters improved after she was treated with therapeutic plasma exchange. We compared our observations on this patient with the current literature and concluded that thrombotic thrombocytopenic purpura is a theoretically plausible yet unreported manifestation of hump-nosed viper bite up to this moment. This study also provides an important message for clinicians to look out for this complication in hump-nosed viper bites since timely treatment can be lifesaving. PMID:24987409

  6. 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

  7. Humoral immune response to ADAMTS13 in acquired thrombotic thrombocytopenic purpura.

    PubMed

    Pos, W; Luken, B M; Sorvillo, N; Kremer Hovinga, J A; Voorberg, J

    2011-07-01

    The apparently spontaneous development of autoantibodies to ADAMTS13 in previously healthy individuals is a major cause of thrombotic thrombocytopenic purpura (TTP). Epitope mapping studies have shown that in most patients antibodies directed towards the spacer domain of ADAMTS13 are present. A single antigenic surface comprising Arg(660) , Tyr(661) and Tyr(665) that contributes to the productive binding of ADAMTS13 to unfolded von Willebrand factor is targeted by anti-spacer domain antibodies. Antibodies directed to the carboxyl-terminal CUB1-2 and TSP2-8 domains have also been observed in the plasma of patients with acquired TTP. As yet it has not been established whether this class of antibodies modulates ADAMTS13 activity. Inspection of the primary sequence of human monoclonal anti-ADAMTS13 antibodies suggests that the variable heavy chain germline gene segment VH1-69 is frequently incorporated. We suggest a model in which 'shape complementarity' between the spacer domain and residues encoded by the VH1-69 gene segment explain the preferential use of this variable heavy chain gene segment. Finally, a model is presented for the development of anti-ADAMTS13 antibodies in previously healthy individuals that incorporates the recent identification of HLA DRB1*11 as a risk factor for acquired TTP. PMID:21535387

  8. Immune Thrombocytopenic Purpura and Gastritis by H. pylori Associated With Type 1 Diabetes Mellitus

    PubMed Central

    Correa, Ricardo; Flores-Guevara, Igor; Espinoza Morales, Frank; Mejia, Christian R

    2016-01-01

    We present the 15th case reported worldwide and 3rd case reported in Latin America of immune thrombocytopenic purpura associated with Type 1 diabetes mellitus in Scopus, MEDLINE, and SciELO. An 11-year-old male patient of mixed ethnicity with immune thrombocytopenic purpura, Type 1 diabetes mellitus, and gastritis due to H. pylori presented to the emergency room with petechiae, ecchymosis, and gingival and conjunctival bleeding that had been worsening for the past three months. The patient had a body mass index of 18.85 kg/m2 (P75). A biochemical analysis showed 1×109 platelets/L, increased prothrombin time, increased partial thromboplastin time, and an HbA1C of 7.84% on admission. He was prescribed a single dose of intravenous methylprednisolone 750 mg in 100 mL of NaCl and daily oral 50 mg prednisolone, with intravenous 250 mg tranexamic acid every eight hours. The patient’s glycemic control was continued with the administration of insulin glargine (30 units every 24 hours) and prandial insulin glulisine (five to eight units per meal). Before admission, the patient was on a prescribed treatment of sitagliptin 50 mg and metformin 850 mg, but this was suspended in the emergency room. For the eradication of H. pylori he was prescribed amoxicillin 500 mg every eight hours, oral clarithromycin 335 mg every 12 hours, and IV omeprazole 40 mg. After 15 days, he showed disease resolution and he was discharged to his home with orders to follow-up with pediatrics, hematology, and endocrinology services. The first-line treatment for immune thrombocytopenic purpura patients with active bleeding and a platelet count < 30,000 platelets/μl is the administration of corticosteroids and inmunoglobulin.

  9. Immune Thrombocytopenic Purpura and Gastritis by H. pylori Associated With Type 1 Diabetes Mellitus.

    PubMed

    Culquichicón-Sánchez, Carlos; Correa, Ricardo; Flores-Guevara, Igor; Espinoza Morales, Frank; Mejia, Christian R

    2016-01-01

    We present the 15th case reported worldwide and 3rd case reported in Latin America of immune thrombocytopenic purpura associated with Type 1 diabetes mellitus in Scopus, MEDLINE, and SciELO. An 11-year-old male patient of mixed ethnicity with immune thrombocytopenic purpura, Type 1 diabetes mellitus, and gastritis due to H. pylori presented to the emergency room with petechiae, ecchymosis, and gingival and conjunctival bleeding that had been worsening for the past three months. The patient had a body mass index of 18.85 kg/m(2) (P75). A biochemical analysis showed 1×10(9) platelets/L, increased prothrombin time, increased partial thromboplastin time, and an HbA1C of 7.84% on admission. He was prescribed a single dose of intravenous methylprednisolone 750 mg in 100 mL of NaCl and daily oral 50 mg prednisolone, with intravenous 250 mg tranexamic acid every eight hours. The patient's glycemic control was continued with the administration of insulin glargine (30 units every 24 hours) and prandial insulin glulisine (five to eight units per meal). Before admission, the patient was on a prescribed treatment of sitagliptin 50 mg and metformin 850 mg, but this was suspended in the emergency room. For the eradication of H. pylori he was prescribed amoxicillin 500 mg every eight hours, oral clarithromycin 335 mg every 12 hours, and IV omeprazole 40 mg. After 15 days, he showed disease resolution and he was discharged to his home with orders to follow-up with pediatrics, hematology, and endocrinology services. The first-line treatment for immune thrombocytopenic purpura patients with active bleeding and a platelet count < 30,000 platelets/μl is the administration of corticosteroids and inmunoglobulin. PMID:27026836

  10. Idiopathic Thrombocytopenic Purpura Presenting in a High School Football Player: A Case Report

    PubMed Central

    Leonard, James C.; Rieger, Mark

    1998-01-01

    Objective: To alert athletic trainers to the signs and symptoms of idiopathic thrombocytopenic purpura and its clinical presentation in order to facilitate immediate intervention. Background: Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenic purpura, is a hemorrhagic disorder that is primarily immunologic in origin but is sometimes triggered by viral infection in children. It has also been associated with heroin and quinine drug use. A reduced platelet count can result in mucosal or deep tissue bleeding, or both, and most importantly, intracranial bleeding. Because football is a collision sport, it is imperative that any player presenting with ITP-type symptoms be removed immediately from all contact and referred to a physician. Differential Diagnosis: Leukemia, aplastic anemia, drug side effects, vitamin deficiency, kidney failure, infection, multiple contusions. Treatment: The traditional first-line treatment consists of corticosteroid medication and time and removal from all physical activities until the blood platelet count is normal and controlled. In quinine-induced ITP, discontinuation of the drug and bedrest are recommended to reduce the risk of major hemorrhage for a 12-to 14-hour period in order to allow the quinine to clear the system and the platelet count to return to normal. Uniqueness: ITP's presentation needs to be differentiated from other disorders. Incorrect diagnosis could seriously jeopardize the athlete, who could develop intracranial and internal bleeding. Conclusions: Recognition of the signs and symptoms associated with ITP is essential to prevent further participation by the athlete. Immediate intervention is needed to determine the severity and to institute appropriate treatment. PMID:16558523

  11. 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

  12. Clopidogrel-Associated Thrombotic Thrombocytopenic Purpura following Endovascular Treatment of Spontaneous Carotid Artery Dissection

    PubMed Central

    Rubano, Jerry A.; Chen, Kwan; Sullivan, Brianne; Vosswinkel, James A.; Jawa, Randeep S.

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disease secondary to platelet aggregation. We present a patient who developed profound thrombocytopenia and anemia 8 days following initiation of therapy with clopidogrel after stent placement for carotid artery dissection. She did not have a disintegrin and metalloproteinase with thrombospondin domain 13 (ADAMTS 13) deficiency. Management included steroids and therapeutic plasma exchange. Clopidogrel has rarely been associated with TTP. Unlike other causes of acquired TTP, the diagnosis of early clopidogrel-associated TTP is largely clinical given the infrequent reduction in ADAMTS 13 activity. PMID:26623244

  13. Surgical treatment of chronic idiopathic thrombocytopenic purpura: results in 107 cases

    SciTech Connect

    Cola, B.; Tonielli, E.; Sacco, S.; Brulatti, M.; Franchini, A.

    1986-07-01

    Between 1972 and 1985, 107 patients with chronic Idiopathic Thrombocytopenic Purpura underwent splenectomy. Platelet life span and sites of sequestration were studied with labelled platelets and external scanning. Medical treatment was always of scarce and transient effectiveness and had considerable side effects. Splenectomy had minimal complications and mortality and caused no hazard of overwhelming sepsis in adults. The results of splenectomy were very satisfying, especially when platelet sequestration was mainly splenic (remission in about 90% of patients). Surgical treatment is at present the most effective in patients with chronic ITP.

  14. Acute immune thrombocytopenic purpura as adverse reaction to oral polio vaccine (OPV)

    PubMed Central

    Jin, Cheng-qiang; Dong, Hai-xin; Sun, Zhuo-xiang; Zhou, Jian-wei; Dou, Cui-yun; Lu, Shu-hua; Yang, Rui-rui

    2013-01-01

    A case of acute immune thrombocytopenic purpura following oral polio vaccine (OPV) is reported. An 82-d-old infant developed purpura at the same day after the second dose of oral polio vaccine. Until the time of hospital admission, the male infant had been in good health and had not received any drugs, and the possible causes of this condition were excluded. His platelet count was 13 × 109/L. Platelet-associated IgG was elevated, but the amount of megakaryocytes in bone marrow aspirates was within the normal range, suggesting immune mechanism-associated thrombocytopenia. The infant recovered with the proper treatment within 30 d. Attention should be paid to OPV-associated thrombocytopenia, though it seems to be less frequent than after natural infections. PMID:23807364

  15. Immune Thrombocytopenic Purpura Associated with Hepatitis A Infection in a Five-year Old Boy: A Case Report

    PubMed Central

    Urganci, N; Kilicaslan, O; Kalyoncu, D; Yilmaz, S

    2014-01-01

    ABSTRACT Acute hepatitis A infection is usually a self-limiting disease and mostly asymptomatic in children younger than six years old. Extrahepatic autoimmune manifestations such as immune thrombocytopenic purpura (ITP) have been reported rarely in children with acute hepatitis A infection. We report herein a paediatric case with ITP which is due to hepatitis A virus infection. PMID:25781273

  16. A Seeming Paradox: Ischemic Stroke in the Context of Idiopathic Thrombocytopenic Purpura.

    PubMed

    Mihalov, Ján; Timárová, Gabriela

    2016-03-01

    Nowadays, we have a relatively sophisticated standard approach to a patient with acute ischemic stroke, including the sequence of diagnostic methods and treatment modalities. In practice, however, we are occasionally confronted with a patient whose medical history or comorbidities force us to make a decision without the support of guidelines. One such situation is the occurrence of acute ischemic stroke in a patient with known idiopathic thrombocytopenic purpura, where a tendency to use thrombolysis, anticoagulants, or antiplatelet agents collides with the fear of life-threatening bleeding. In this review, we try to outline current understanding of the pathophysiology of "paradoxical" ischemic events in this illness characterized by thrombocytopenia and to summarize clinical experience from case reports dealing with this topic, which could help us to rely on more than individual opinion seen through a purely "neurological" or "hematological" prism. PMID:25115760

  17. What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura.

    PubMed

    Sadler, J Evan

    2015-12-01

    Severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency causes thrombotic thrombocytopenic purpura (TTP), which is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and the absence of oliguric or anuric renal failure. However, some patients with this constellation of findings do not have ADAMTS13 deficiency, and some patients with ADAMTS13 deficiency have renal failure or relatively normal blood counts. Consequently, many investigators and clinicians have incorporated severe ADAMTS13 deficiency into the case definition of TTP. This change has facilitated the timely initiation of treatment for patients with atypical clinical features who otherwise would not be recognized as having TTP. Conversely, excluding severe ADAMTS13 deficiency focuses attention on the diagnosis and treatment of other causes of thrombotic microangiopathy that require different treatment. The rapid return of ADAMTS13 data is important to make the best use of this information. PMID:26637781

  18. Peliosis hepatis presenting with massive hepatomegaly in a patient with idiopathic thrombocytopenic purpura

    PubMed Central

    Kim, Sun Bean; Kim, Do Kyung; Byun, Sun Jeong; Park, Ji Hye; Choi, Jin Young; Park, Young Nyun

    2015-01-01

    Peliosis hepatis is a rare condition that can cause hepatic hemorrhage, rupture, and ultimately liver failure. Several authors have reported that peliosis hepatis develops in association with chronic wasting disease or prolonged use of anabolic steroids or oral contraceptives. In this report we describe a case in which discontinuation of steroid therapy improved the condition of a patient with peliosis hepatis. Our patient was a 64-year-old woman with a history of long-term steroid treatment for idiopathic thrombocytopenic purpura . Her symptoms included abdominal pain and weight loss; the only finding of a physical examination was hepatomegaly. We performed computed tomography (CT) and magnetic resonance imaging (MRI) of the liver and a liver biopsy. Based on these findings plus clinical observations, she was diagnosed with peliosis hepatis and her steroid treatment was terminated. The patient recovered completely 3 months after steroid discontinuation, and remained stable over the following 6 months. PMID:26770928

  19. Anti-interleukin-2 receptor antibody (daclizumab) treatment of corticosteroid-refractory autoimmune thrombocytopenic purpura.

    PubMed

    Fogarty, Patrick F; Seggewiss, Ruth; McCloskey, Donna Jo; Boss, Carol A; Dunbar, Cynthia E; Rick, Margaret E

    2006-02-01

    We administered daclizumab, a humanized monoclonal anti-interleukin-2 receptor (IL-2R) antibody, to 11 patients with corticosteroid-refractory autoimmune thrombocytopenic purpura (AITP) every 2 weeks for five treatments. Of nine evaluable patients, one individual experienced a partial response. Lymphocyte phenotyping by flow cytometry indicated post-treatment binding of IL-2Ra by daclizumab in all patients. Mid-study serum soluble IL-2R levels in all patients increased 4-15 -fold over baseline values (p=0.004). Despite these measurable immunologic effects, blockade of the IL-2/IL-2R axis did not effectively abrogate the autoimmune response in this group of patients with corticosteroid-refractory AITP. PMID:16461323

  20. Neglect-induced pseudo-thrombotic thrombocytopenic purpura due to vitamin B12 deficiency.

    PubMed

    Asano, Takeshi; Narazaki, Hidehiko; Kaizu, Kiyohiko; Matsukawa, Shouhei; Takema-Tochikubo, Yuki; Fujii, Shuichi; Saitoh, Nobuyuki; Mashiko, Kunihiko; Fujino, Osamu

    2015-10-01

    Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15-year-old girl who had been neglected, which might have caused pseudo-TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect. PMID:26387768

  1. Thrombotic thrombocytopenic purpura (TTP) following coronary artery bypass: case series and review of the literature.

    PubMed

    Jubelirer, Steven J; Ratliff, Heather L; Cotes, Deborah J; Riley, Mary Ann; Welch, Christine A

    2015-01-01

    We reviewed 10 cases of thrombotic thrombocytopenic purpura (TTP) following cardiac surgery since November 1998. The object of the study was to define the natural history of post-CABG-TTP and to assess response to therapy. All patients underwent CABG; four also underwent aortic valve replacement and six mitral valve replacement. Eight patients had mental status changes and/or unexplained fever. All patients received plasmapheresis ranging from 5 to 24 days and nine required hemodialysis or continuous renal replacement therapy. All had significant improvement in their platelet count, LDH, renal function, and mental status changes at discharge. None of the five surviving patients has relapsed at follow-up ranging from 8 months to 6 years. Early recognition of this syndrome and early institution of plasmapheresis are important for a favorable outcome. PMID:25665272

  2. Absolute immature platelet count helps differentiate thrombotic thrombocytopenic purpura from hypertension-induced thrombotic microangiopathy.

    PubMed

    Zheng, Yan; Hong, Hong; Reeves, Hollie M; Maitta, Robert W

    2014-08-01

    ADAMTS13 activity measurement is used in the diagnostic algorithm of thrombotic thrombocytopenic purpura (TTP), but results may not be available before initiation of therapeutic plasma exchange (TPE). The immature platelet fraction (%-IPF) and the calculated absolute immature platelet count (A-IPC) represent a test of real-time thrombopoiesis, and can be performed in most laboratories using automated analyzers. Here we report on using A-IPC kinetics to exclude idiopathic TTP in a patient with severe hypertension, thrombocytopenia, and acute renal failure, which was confirmed by a normal ADAMTS13. The complete resolution of thrombocytopenia occurred once blood pressure was controlled favoring a diagnosis of hypertension-induced thrombotic microangiopathy. PMID:25130726

  3. Spontaneous bilateral peripapillary, subhyaloid and vitreous hemorrhage with only minor platelet deficit in idiopathic thrombocytopenic purpura

    PubMed Central

    Wan-Wei, Loo; Tengku-Norina, Tuan-Jaffar; Azma-Azalina, Ahmad-Alwi; Zulkifli, Abdul-Ghani; Zunaina, Embong

    2014-01-01

    A 45-year-old female with underlying idiopathic thrombocytopenic purpura (ITP) complained of acute onset of reduced vision and floaters, in both eyes, for 3 weeks. Visual acuity was 6/36 and 6/60 in the right eye and left eye, respectively. Ophthalmoscopy showed bilateral peripapillary, subhyaloid and vitreous hemorrhage. Hematological evaluation revealed moderate anemia (hemoglobin: 93 g/L) and mild thrombocytopenia (platelets: 120×109/L). She was co-managed by a hematologist and ophthalmologists; she was treated medically. Follow-up care during the next 6 weeks revealed spontaneous, partially resolving hemorrhage, with improvement of visual acuity. The purpose of this case report is to highlight ophthalmic involvement of ITP in this patient, despite her only-mild thrombocytopenia, and her spontaneous recovery, despite her receiving only medical treatment. PMID:24493935

  4. Ciprofloxacin-Induced Thrombotic Thrombocytopenic Purpura: A Case of Successful Treatment and Review of the Literature

    PubMed Central

    Hashmi, Hafiz Rizwan Talib; Diaz-Fuentes, Gilda; Jadhav, Preeti; Khaja, Misbahuddin

    2015-01-01

    A 49-year-old African American woman was admitted to our hospital with abdominal pain, nausea, vomiting, lethargy, and confusion. She was receiving ciprofloxacin for a urinary-tract infection prior to admission. Laboratory examination revealed anemia, thrombocytopenia, elevated lactate dehydrogenase, and serum creatinine. Peripheral smear showed numerous schistocytes, and the patient was diagnosed with thrombotic thrombocytopenic purpura (TTP). Ciprofloxacin was identified as the offending agent. The patient received treatment with steroids and plasmapheresis, which led to rapid clinical recovery. This is the first case to our knowledge of successfully treated ciprofloxacin-induced TTP; previously reported cases had fulminant outcomes. Quinolones are an important part of the antibiotic armamentarium, and this case can raise awareness of the association between quinolones and TTP. A high index of suspicion for detection and early and aggressive management are vitally important for a successful outcome. PMID:26587293

  5. Peliosis hepatis presenting with massive hepatomegaly in a patient with idiopathic thrombocytopenic purpura.

    PubMed

    Kim, Sun Bean; Kim, Do Kyung; Byun, Sun Jeong; Park, Ji Hye; Choi, Jin Young; Park, Young Nyun; Kim, Do Young

    2015-12-01

    Peliosis hepatis is a rare condition that can cause hepatic hemorrhage, rupture, and ultimately liver failure. Several authors have reported that peliosis hepatis develops in association with chronic wasting disease or prolonged use of anabolic steroids or oral contraceptives. In this report we describe a case in which discontinuation of steroid therapy improved the condition of a patient with peliosis hepatis. Our patient was a 64-year-old woman with a history of long-term steroid treatment for idiopathic thrombocytopenic purpura . Her symptoms included abdominal pain and weight loss; the only finding of a physical examination was hepatomegaly. We performed computed tomography (CT) and magnetic resonance imaging (MRI) of the liver and a liver biopsy. Based on these findings plus clinical observations, she was diagnosed with peliosis hepatis and her steroid treatment was terminated. The patient recovered completely 3 months after steroid discontinuation, and remained stable over the following 6 months. PMID:26770928

  6. Lower Extremity Wounds in Patients With Idiopathic Thrombocytopenic Purpura and Systemic Lupus Erythematosus.

    PubMed

    Akita, Sadanori

    2015-09-01

    Infections in lower extremities are sometimes concerned with systemic immunological disorders such as idiopathic thrombocytopenic purpura and systemic lupus erythematosus, which are treated with systemic steroids. Steroid therapy impairs the epithelial wound healing and with systemic condition, especially with systemic lupus erythematosus, the wound is susceptible for infection. Even a pyoderma gangrenosum sometimes occurs in a patient with idiopathic thrombocytopenic purpura with an incisional wound of hernia. The severe signs and symptoms are the deep skin and soft tissue infections, mainly caused by group A streptococcus, composed of necrotizing fasciitis and muscle necrosis. Medically suspected necrotizing fasciitis patients should be empirically and immediately administered with broad-spectrum antibiotics, which may cover the common suspected pathogens. In type I (polymicrobial) infection, the selection of antimicrobial should be based on medical history and Gram staining and culture. The coverage against anaerobes is important in type I infection. Metronidazole, clindamycin, or beta-lactams with beta-lactamase inhibitor or carbapenems are the treatment of choice against anaerobes, while early surgical debridement-wide enough and deep enough-is the core treatment of necrotizing fasciitis and results in significantly better mortality compared with those who underwent surgery after a few hours of delay. When necrotizing fasciitis is considered and the patient is brought to the operation room, aggressive and extensive surgical debridement is explored. Tissue involved should be completely removed until no further evidence of infection is seen. When further debridement is required, the patient must return to the operating room immediately. In this context, the temporal coverage using the artificial dermis after debridement is useful because there is no loss of the patient's own tissue and yet it is easier for "second-look" surgery or secondary reconstruction, and extensive enough debridement is always the mainstay of the therapy. PMID:26353824

  7. [Successful treatment with rituximab of a patient with coincident acquired hemophilia A and thrombotic thrombocytopenic purpura].

    PubMed

    Yamamoto, Kazuhiko; Sandou, Yasuhisa; Niiya, Masami; Osada, Yuuki; Ikeuchi, Kazuhiro; Yamamoto, Yoshikazu; Shiote, Yasuhiro; Makita, Masanori; Imajo, Kenji

    2015-11-01

    A 66-year-old man was admitted for oral hemorrhage, purpura, and APTT prolongation. Factor VIII (FVIII) activity was decreased, due to the presence of FVIII inhibitor. He was diagnosed with acquired hemophilia A (AHA) and treated with prednisolone. Eight months later, the FVIII inhibitor titer again increased. Upon readmission, thrombocytopenia and autoimmune hemolytic anemia were found. We suspected Evans syndrome accompanied by AHA, and we treated the patient with IVIG. However, his platelet count did not increase. Speech disturbance and delirium were observed from the 12th day of hospitalization. He was subsequently diagnosed with thrombotic thrombocytopenic purpura (TTP) because ADAMTS13 inhibitor was detected, causing a decrease in ADAMTS13 activity. We initiated plasma exchange (PE) and steroid-pulse therapy. After PE for 3 days, laboratory test results and psychiatric symptoms showed dramatic improvement. However, after a 2-day period without PE, the patient's platelet count decreased markedly. Therefore, we administered rituximab to eliminate these inhibitors. His platelet count recovered rapidly, and we were able to gradually wean the patient from PE. After two additional administrations of rituximab, neither inhibitor was detected. To date, the patient has remained in complete remission for approximately 3 years. PMID:26666718

  8. Vitamin B12 Deficiency and Hemoglobin H Disease Early Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Series of Unfortunate Events

    PubMed Central

    Andreadis, Panagiotis; Theodoridou, Stamatia; Pasakiotou, Marily; Arapoglou, Stergios; Gigi, Eleni; Vetsiou, Evaggelia; Vlachaki, Efthymia

    2015-01-01

    We herein would like to report an interesting case of a patient who presented with anemia and thrombocytopenia combined with high serum Lactic Dehydrogenase where Thrombotic Thrombocytopenic Purpura was originally considered. As indicated a central venous catheter was inserted in his subclavian vein which led to mediastinal hematoma and finally intubation and Intensive Care Unit (ICU) hospitalization. After further examination patient was finally diagnosed with B12 deficiency in a setting of H hemoglobinopathy. There have been previous reports where pernicious anemia was originally diagnosed and treated as Thrombotic Thrombocytopenic Purpura but there has been none to our knowledge that was implicated with hemothorax and ICU hospitalization or correlated with thalassemia and we discuss the significance of accurate diagnosis in order to avoid adverse reactions and therapy implications. PMID:26609455

  9. 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

  10. Two novel heterozygote missense mutations of the ADAMTS13 gene in a child with recurrent thrombotic thrombocytopenic purpura

    PubMed Central

    Rossio, Raffaella; Ferrari, Barbara; Cairo, Andrea; Mancini, Ilaria; Pisapia, Giovanni; Palazzo, Giulia; Peyvandi, Flora

    2013-01-01

    Background Thrombotic thrombocytopenic purpura is a rare, life-threatening disease characterised by microangiopathic haemolytic anaemia, thrombocytopenia and symptoms related to organ ischaemia, mainly involving the brain and the kidney. It is associated with a deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. The congenital form (Upshaw-Schulman syndrome) is rare and is associated with mutations of the ADAMTS13 gene on chromosome 9q34. The clinical symptoms of congenital thrombotic thrombocytopenic purpura are variable, with some patients developing their first episode during the neonatal period or childhood and others becoming symptomatic in adulthood. Materials and methods We describe a case of thrombotic thrombocytopenic purpura, who presented to our attention with a relapsing form of the disease: the first episode occurred at the age of 13 months. Phenotype and genotype tests were performed in the patient and his family. Results The undetectable level of ADAMTS13 in the patient was caused by two novel heterozygote missense mutations on the ADAMTS13 gene: one mutation is c.788C > T (p.Ser263Phe) on exon 7 and the second is c.3251G > A (p.Cys1084Tyr) on exon 25 of the ADAMTS13 gene. All the relatives who have been investigated were found to carry one of these missense mutations in a heterozygous state. Discussion Although Upshaw-Schulman syndrome is a rare disease, it should be considered in all children with thrombocytopenia and jaundice in the neonatal period. In fact, once a child is confirmed to carry mutations of the ADAMTS13 gene causing early thrombotic thrombocytopenic purpura, prophylactic treatment should be started to avoid recurrence of symptoms. Genotype tests of relatives would also be important for those women in the family who could be carriers of ADAMTS13 mutations, particularly during pregnancy. PMID:23058857

  11. 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.

  12. Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents thrombotic thrombocytopenic purpura in murine models.

    PubMed

    Pickens, Brandy; Mao, Yingying; Li, Dengju; Siegel, Don L; Poncz, Mortimer; Cines, Douglas B; Zheng, X Long

    2015-05-21

    ADAMTS13 metalloprotease cleaves von Willebrand factor (VWF), thereby inhibiting platelet aggregation and arterial thrombosis. An inability to cleave ultralarge VWF resulting from hereditary or acquired deficiency of plasma ADAMTS13 activity leads to a potentially fatal syndrome, thrombotic thrombocytopenic purpura (TTP). Plasma exchange is the most effective initial therapy for TTP to date. Here, we report characterization of transgenic mice expressing recombinant human ADAMTS13 (rADAMTS13) in platelets and its efficacy in inhibiting arterial thrombosis and preventing hereditary and acquired antibody-mediated TTP in murine models. Western blotting and fluorescent resonance energy transfer assay detect full-length rADAMTS13 protein and its proteolytic activity, respectively, in transgenic (Adamts13(-/-)Plt(A13)), but not in wild-type and Adamts13(-/-), platelets. The expressed rADAMTS13 is released on stimulation with thrombin and collagen, but less with 2MesADP. Platelet-delivered rADAMTS13 is able to inhibit arterial thrombosis after vascular injury and prevent the onset and progression of Shigatoxin-2 or recombinant murine VWF-induced TTP syndrome in mice despite a lack of plasma ADAMTS13 activity resulting from the ADAMTS13 gene deletion or the antibody-mediated inhibition of plasma ADAMTS13 activity. These findings provide a proof of concept that platelet-delivered ADAMTS13 may be explored as a novel treatment of arterial thrombotic disorders, including hereditary and acquired TTP, in the presence of anti-ADAMTS13 autoantibodies. PMID:25800050

  13. 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

  14. Long-Term Outcomes of Laparoscopic Splenectomy Versus Open Splenectomy for Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Qu, Yikun; Xu, Jian; Jiao, Chengbin; Cheng, Zhuoxin; Ren, Shiyan

    2014-01-01

    The long-term outcomes of laparoscopic splenectomy (LS) versus open splenectomy (OS) in patients with idiopathic thrombocytopenic purpura (ITP) are not known. A retrospective analysis of 73 patients who underwent splenectomy (32 LS and 41 OS) for refractory ITP between April 2003 and June 2012 was conducted. LS was associated with shorter hospital stay (P = 0.01), less blood loss and blood transfusion during surgery, quicker resumption of oral diet (P < 0.0001), and earlier drain removal (P < 0.01). Conversion to OS was required in 4 patients (12.5%). Operation time was significantly longer in LS (P < 0.0001). Deep venous thrombosis (DVT) was observed in 1 patient after LS and in 4 patients after OS (P = 0.52). One patient died from intraperitoneal bleeding after OS, another patient developed pulmonary embolism. Median follow-up of 36 months was performed in LS group (29 of 32, 91%) and of 46 months in OS group (35 of 41, 85%), 25 patients (86%) in LS group and 32 (91%) in OS group reached sustained complete response (P = 0.792). Kaplan-Meier analysis showed that there was no significant difference in the relapse-free survival rate between the groups (P = 0.777). In conclusion, the long-term outcome of laparoscopic splenectomy is not different from that of open splenectomy for patients with ITP. PMID:24833154

  15. The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Rottenstreich, Amihai; Hochberg-Klein, Sarit; Rund, Deborah; Kalish, Yosef

    2016-05-01

    Thrombotic thrombocytopenic purpura (TTP) is an acute, thrombotic microangiopathy with a high mortality rate if left untreated. Plasma exchange (PEX) is the current standard of care. However, a significant number of patients are refractory to this treatment. N-acetylcysteine (NAC) was recently suggested as a potential therapeutic adjunct for patients with TTP. This study reports a series of three patients with TTP successfully treated with NAC in addition to standard therapy. Detailed chart reviews on these patients were conducted. We discuss clinical features, laboratory findings and management of three patients who presented with microangiopathic hemolytic anemia and thrombocytopenia. Anti-ADAMTS13 antibodies and low levels of ADAMTS13 were detected and confirmed the diagnosis of acquired TTP. Based upon their severe presentation or lack of response to initial treatment with PEX, corticosteroids and other immunosuppressive agents, NAC was added. Under this combined treatment, all three patients hada significant clinical improvement of symptoms with concurrent normalization of platelet count and ADAMTS13 activity level. This report highlights the potential therapeutic utility of NAC in the treatment of TTP. Randomized controlled studies will be required to better characterize the risk-to-benefit ratio of NAC in the treatment of TTP. PMID:26245827

  16. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines.

    PubMed

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy. PMID:26740871

  17. Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura

    SciTech Connect

    Syrjaelae, M.T.Sa.; Savolainen, S.; Nieminen, U.; Gripenberg, J.; Liewendahl, K.; Ikkala, E. )

    1989-09-01

    Splenic dynamics of {sup 111}In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of {sup 111}In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 {plus minus} 0.7 min vs. 3.6 {plus minus} 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 {plus minus} 5 min vs. 13.2 {plus minus} 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.

  18. 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.

  19. Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency.

    PubMed

    Fan, Xinping; Kremer Hovinga, Johanna A; Shirotani-Ikejima, Hiroko; Eura, Yuka; Hirai, Hidenori; Honda, Shigenori; Kokame, Koichi; Taleghani, Magnus Mansouri; von Krogh, Anne-Sophie; Yoshida, Yoko; Fujimura, Yoshihiro; Lämmle, Bernhard; Miyata, Toshiyuki

    2016-03-01

    The congenital form of thrombotic thrombocytopenic purpura (TTP) is caused by genetic mutations in ADAMTS13. Some, but not all, congenital TTP patients manifest renal insufficiency in addition to microangiopathic hemolysis and thrombocytopenia. We included 32 congenital TTP patients in the present study, which was designed to assess whether congenital TTP patients with renal insufficiency have predisposing mutations in complement regulatory genes, as found in many patients with atypical hemolytic uremic syndrome (aHUS). In 13 patients with severe renal insufficiency, six candidate complement or complement regulatory genes were sequenced and 11 missense mutations were identified. One of these missense mutations, C3:p.K155Q mutation, is a rare mutation located in the macroglobulin-like 2 domain of C3, where other mutations predisposing for aHUS cluster. Several of the common missense mutations identified in our study have been reported to increase disease-risk for aHUS, but were not more common in patients with as compared to those without renal insufficiency. Taken together, our results show that the majority of the congenital TTP patients with renal insufficiency studied do not carry rare genetic mutations in complement or complement regulatory genes. PMID:26830967

  20. Late-Onset Immune Thrombocytopenic Purpura After Withdrawal of Interferon Treatment for Chronic Hepatitis C Infection

    PubMed Central

    Hsiao, Chien-Hao; Tseng, Kuo-Chih; Tseng, Chih-Wei; Tung, Chien-Hsueh

    2015-01-01

    Abstract Immune thrombocytopenic purpura (ITP) is a life-threatening complication following pegylated interferon alpha (PEG-IFN) plus ribavirin treatment, the standard treatment for hepatitis C virus (HCV) infection. We reported a rare case with late-onset ITP after withdrawal of PEG-IFN treatment. A 53-year-old male with hepatitis C developed massive gum bleeding and a severe, reversible, immune thrombocytopenia 2 weeks after cessation of PEG-IFN treatment for HCV due to anemia and depression. The platelet count decreased to 4000 cells/μL. The HCV viral load was undetectable at the end of PEG-IFN treatment and during follow-up for 5 months. Other potential autoimmune disorders were ruled out. Late-onset ITP associated with PEG-IFN treatment was diagnosed. The patient was treated successfully with steroid and azathioprine. Platelet count gradually increased to 117 × 103 cells/μL on the 18th day after admission. ITP is a rare complication in patients with hepatitis C or in patients who received PEG-IFN treatment. The particular case supported that it may occur even after withdrawal of PEG-IFN treatment. Physicians should be aware of this late-onset complication. PMID:26313770

  1. [Sudden death associated with myocardial damage caused by microthrombi in a patient with thrombotic thrombocytopenic purpura].

    PubMed

    Yamamoto, Kiyoko; Hattori, Yukinori; Shimada, Koki; Araki, Yoko; Adachi, Tatsuya; Tsushita, Keitaro

    2015-11-01

    We describe a 35-year-old woman with Down's syndrome who was admitted to a clinic with anorexia and vomiting. Since laboratory findings showed anemia (Hb 7.4 g/dl) and thrombocytopenia (0.5 × 10⁴/μl), she was transferred to our hospital for treatment. Further laboratory examinations revealed schistocytes, LDH elevation, and a negative Coombs' test. Thrombotic thrombocytopenic purpura (TTP) was suspected. Plasma exchange (PEX) and prednisolone administration were thus immediately initiated. Prior to these treatments, ADAMTS13 activity was less than 5% and inhibitors were detected at a level of 0.8 Bethesda U/ml. Although her platelet count had risen to 13.0 × 10⁴/μl by day 6 (post 4 sessions of PEX), it had decreased to 1.8 × 10⁴/μl on day 7. Despite ongoing PEX, thrombocytopenia persisted. On day 21, she suddenly died. Autopsy findings revealed no evidence of myocardial necrosis or coronary artery thrombosis. Extensive microthrombi were, however, detected in precapillary arterioles, capillaries, and post-capillary venules of the heart. Therefore, this patient's sudden death was clinically suspected to have been caused by cardiomyopathy, which had produced cardiogenic shock. PMID:26666721

  2. Adult idiopathic thrombocytopenic purpura (ITP)--a prospective tracking of its natural history.

    PubMed

    Kueh, Y K

    1995-08-01

    Thirty-seven Asian patients (30 women, 7 men) with chronic idiopathic thrombocytopenic purpura (ITP) followed prospectively for 4 to 15 years showed a highly variable clinical course. The women as a group had a much lower initial platelet count than the men (28 x 10(9)/l versus 54 x 10(9)/l). All the women but only 2 men required treatment for symptomatic thrombocytopenia. Six women developed secondary autoimmune disorders (4 systemic lupus erythematosus and 2 Evan's syndrome) after 14 to 33 months of clinical follow up. Although their responses to corticosteroid therapy were suboptimal when initiated for ITP, these 6 patients uniformly demonstrated a complete platelet response when corticosteroid treatment was re-introduced following the evolution of secondary autoimmune disorders. Four of the 5 untreated men were over 55 years of age. Their mild to moderate thrombocytopenia was discovered incidentally and they remained symptom-free after a follow up of at least 5 years. The overall response rates of this cohort of Asian patients to corticosteroid therapy and splenectomy are compared with those reported from the West. Three deaths are recorded in this study, one from intracranial haemorrhage and 2 gram negative septicaemia in steroid-dependent postsplenectomy patients. The variable behaviour of this cohort of ITP patients emphasises the need for individualised management. Asymptomatic thrombocytopenia can be observed without treatment. Two fatalities from gram negative septicaemia in asplenic, steroid-dependent patients caution against the hasty recommendation of splenectomy for refractory ITP. PMID:8919147

  3. Interactions of von Willebrand factor and ADAMTS13 in von Willebrand disease and thrombotic thrombocytopenic purpura.

    PubMed

    Budde, U; Schneppenheim, R

    2014-01-01

    The function of von Willebrand factor (VWF), a huge multimeric protein and a key factor in platelet dependent primary haemostasis, is regulated by its specific protease ADAMTS13. The ADAMTS13 dependent degradation of VWF to its proteolytic fragments can be visualized as a characteristic so-called triplet structure of individual VWF oligomers by multimer analysis. Lack of VWF high molecular weight multimers (VWF-HMWM) or their pathologically enhanced degradation underlies a particular type of von Willebrand disease, VWD type 2A with a significant bleeding tendency, and may also be observed in acquired von Willebrand syndrome due to cardiovascular disease. In these conditions multimer analysis is an obligatory and powerful tool for diagnosis of VWD. The opposite condition, the persistence of ultralarge VWF (UL-VWF) multimers may cause the microangiopathic life-threatening disorder thrombotic thrombocytopenic purpura (TTP). During the course of active TTP, UL-VWF is consumed in the hyaline thrombi formed in the microvasculature which will ultimately result in the loss of UL-VWF and VWF-HMWM. Therefore, VWF multimer analysis is not a valid tool to diagnose TTP in the active phase of disease but may be helpful for the diagnosis of TTP patients in remission. PMID:25010251

  4. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines

    PubMed Central

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy. PMID:26740871

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

    PubMed Central

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

    2013-01-01

    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

  6. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

    PubMed

    Maghbool, Maryam; Maghbool, Masood; Shahriari, Mehdi; Karimi, Mehran

    2009-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10-15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×10(9)/L) or partial (platelet count between 50 and 150×10(9)/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients. PMID:21589818

  7. Bilateral ureteral stones and spontaneous perirenal hematoma in a patient with chronic idiopathic thrombocytopenic purpura.

    PubMed

    Akyüz, Mehmet; Cal??kan, Selahattin; Kaya, Cevdet

    2012-07-01

    Idiopathic thrombocytopenic purpura (ITP) is an immune thrombocytopenia with a usually benign clinical course. Bleedings are mostly of the mucocutaneous type with mild symptoms. Massive bleedings requiring transfusion are rarely seen, unless the number of platelets decreases to extremely low levels. In this case, bilateral perirenal hematoma and bilateral distal ureteral stones were detected on a non-contrast computed tomography scan of a 57-year-old male patient who developed macroscopic hematuria during his treatment in the clinics of internal medicine because of left flank pain and diffuse petechial rashes all over his body. The patient, who had been receiving chronic ITP treatment for 1 year, had a very low platelet count (4,000/mm(3)). The patient was prescribed bed rest, and his platelet count increased to a safe level for surgical intervention of above 50,000/mm(3) with administration of prednisolone, intravenous immune globulin, and platelet suspension. A stone-free state was achieved after bilateral ureterorenoscopy and pneumatic lithotripsy. A conservative approach was followed for the perirenal hematoma. Upon regression of the perirenal hematoma, the patient was discharged at 9 weeks postoperatively. PMID:22866224

  8. Neonates born to mothers with immune thrombocytopenic purpura: a single-center experience of 20 years.

    PubMed

    Bayhan, Turan; Tavil, Betül; Korkmaz, Ayşe; Ünal, Şule; Hanalioğlu, Damla; Yiğit, Şule; Gümrük, Fatma; Çetin, Mualla; Yurdakök, Murat

    2016-01-01

    Neonates born to mothers with immune thrombocytopenic purpura (ITP) have an increased risk of having thrombocytopenia and bleeding. The aim of our study was to determine maternal and fetal factors that can predict bleeding risk in neonates born to mothers with ITP, and effective treatment strategies by retrospective analysis of our single-center data. We performed a retrospective data review of neonates that were recorded as 'neonates born to mothers with ITP' in the Neonatal ICU of Hacettepe University, Ihsan Dogramacı Children's Hospital, Ankara, Turkey. Medical records of 36 neonates born from 35 mothers were analyzed. Among the 36 neonates born to mothers with ITP, thrombocytopenia (platelet count of less than 150 × 10/l) was detected in 20 (56.0%) neonates on the first day of life. Twelve of the 20 neonates with thrombocytopenia (60.0%) required treatment to increase the platelet counts. Clinical findings related to thrombocytopenia occurred in three (15.0%) neonates, but none of them presented with severe bleeding. There was no statistically significant association between neonatal lowest platelet count and maternal lowest platelet count, maternal platelet count at the time of delivery, and duration of thrombocytopenia, respectively. Neonates born to mothers with ITP have an increased tendency to develop thrombocytopenia, but severe bleeding is very rare in these neonates. Clinicians should pay special attention to follow these neonates. According to our results, both intravenous immunoglobulin and methyl prednisolone were found to be in equivalent efficacy for the treatment of neonatal thrombocytopenia due to maternal ITP. PMID:26258676

  9. 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

  10. Two Types of Renovascular Lesions in Lupus Nephritis with Clinical Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Sekine, Akinari; Hasegawa, Eiko; Hiramatsu, Rikako; Mise, Koki; Sumida, Keiichi; Ueno, Toshiharu; Yamanouchi, Masayuki; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi

    2015-01-01

    Renovascular lesions of lupus nephritis (LN) were classified into five categories by D'Agati in Heptinstall's Pathology of the Kidney, with thrombotic microangiopathy (TMA) and clinical thrombotic thrombocytopenic purpura (TTP) being combined. We encountered 2 cases with histological LN (class III and lass V), and they presented with clinical features of TTP, such as acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, fever, and central neurologic symptoms. Immunosuppressive therapy with plasmapheresis was performed in both patients. Case 1 progressed to end-stage renal failure requiring dialysis and died, while case 2 responded to treatment. In case 1, small renal arteries showed positive mural staining for IgG and C3, while intraluminal material was negative for IgG and C3 [although it was positive for phosphotungstic acid-hematoxylin (PTAH), indicating fibrin deposition]. In case 2, small renal arteries showed mural staining for IgG, C1q, and C3, with the intraluminal material also being positive for these immunoglobulins, but negative for PTAH. These cases suggest that immunosuppressive therapy with plasmapheresis can control LN when intravascular thrombosis is related to immune complexes associated with activation of the early complement components C1q and C3. In contrast, immunosuppressive therapy with plasmapheresis may not be effective when intravascular thrombosis is unrelated to these factors and involves fibrin deposition. Accordingly, in LN patients with clinical features of TTP, we report two types of renovascular lesions, in addition to typical vascular change of TMA with no immune deposits seen in nonlupus patients. PMID:26558253

  11. Eltrombopag enhances platelet adhesion by upregulating the expression of glycoprotein VI in patients with chronic immune thrombocytopenic purpura.

    PubMed

    Chiou, Tzeon-Jye; Chang, Yi-Fang; Wang, Ming-Chung; Kao, Chen-Wei; Lin, Hsuan-Yu; Chen, Tsai-Yun; Hsueh, Erh-Jung; Lan, Yii-Jenq; Sung, Yung-Chuan; Lin, Sheng-Feng; Bai, Li-Yuan; Chen, Caleb G

    2015-12-01

    Eltrombopag, a thrombopoietin receptor agonist, has been approved for the treatment of patients with immune thrombocytopenia because of its abilities to enhance platelet production and reduce hemorrhage. Both platelet count and platelet adhesion are crucial to stop bleeding. Although eltrombopag is known to improve platelet counts, its effects on platelet adhesion are not yet known. This study aimed to assess the efficacy of eltrombopag on platelet production and platelet adhesive affinity. To evaluate the efficacy of low-dose eltrombopag (25 mg) for patients with chronic refractory immune thrombocytopenic purpura (ITP) and to determine the ex vivo platelet adhesion ability before and after treatment with eltrombopag, we conducted an open-label, multicenter study in which 25 Taiwanese patients with chronic ITP were enrolled. During the 6-month evaluation, the starting and maximum doses of eltrombopag were 25 and 50 mg, respectively, to maintain the platelet count of ?50,000 per ?L. Flow-based adhesion assay was used to detect the percentage of platelets adhering to immobilized von Willebrand factor-collagen on microslides. Of the enrolled patients, 48% achieved a platelet count of ?50,000 per ?L. Interestingly, 83% of all responders required 25 mg of eltrombopag daily to achieve the target platelet count. In addition, the percentage of bleeding patients was significantly reduced in both responders and nonresponders by 50% from the baseline level throughout the treatment period. The ex vivo platelet adhesion capacity was elevated after the 6-month eltrombopag treatment in both responders and nonresponders. Furthermore, glycoprotein VI (GPVI) expression was significantly upregulated after treatment with eltrombopag. Low-to-intermediate dose of eltrombopag showed good efficacy to expedite platelet production and augment platelet adhesion. These 2 factors might explain the efficacy of eltrombopag in ameliorating hemorrhage in patients with ITP. PMID:26477577

  12. Acquired amegakaryocytic thrombocytopenic purpura induced by percutaneous ethanol injection during treatment of hepatocellular carcinoma: A case report

    PubMed Central

    AI, DING-LUN; LI, BO-TAO; PENG, XIAO-MING; ZHANG, LIN-ZHI; WANG, JING-YAN; ZHAO, YUN; YANG, BIN; YU, QIANG; LIU, CHUN-ZI; YANG, NING; WANG, HUA-MING; ZHOU, LIN

    2016-01-01

    Percutaneous ethanol injection is an important localized treatment method for patients presenting with hepatocellular carcinoma (HCC). Among the advantages of percutaneous ethanol injection are its minimal invasiveness, simplicity, low cost and low risk of complications. However, the increasing popularity of percutaneous ethanol injection has resulted in serious adverse effects attributed to individual variations. The present study describes the case of a patient who exhibited acquired amegakaryocytic thrombocytopenic purpura, caused by percutaneous ethanol injection treatment for HCC. This complication was promptly identified, and platelet transfusion and injection of recombinant human interleukin-11 resulted in a rapid recovery of the patient's platelet count. Attention should be given to this rare complication in patients administered percutaneous ethanol injection treatment for HCC. PMID:26870287

  13. Opana ER abuse and thrombotic thrombocytopenic purpura (TTP)-like illness: a rising risk factor in illicit drug users

    PubMed Central

    Kapila, Aaysha; Chhabra, Lovely; Chaubey, Vinod K; Summers, Jeffery

    2014-01-01

    We report the case of a 22 year-old-woman who presented with upper extremity cellulitis secondary to an infiltration of illicit intravenous drug use. She confessed to the intravenous use of Opana ER (an extended release oral formulation of oxymorphone) which is an opioid drug approved only for oral use. She was found to have clinical evidence of profound thrombotic microangiopathy which resulted due to the intravenous use of Opana ER. She showed full clinical improvement after withholding drug and supportive clinical care. Recent report of Opana ER intravenous abuse was published from Tennessee county and has now been increasingly recognised as one of the causes of thrombocytopenia which mimicks clinically as thrombotic thrombocytopenic purpura. Physicians should be aware of this association as the lack of familiarity to this can pose serious management dilemmas for our patients (especially the polysubstance abusers). PMID:24591390

  14. ADAMTS13 and anti-ADAMTS13 autoantibodies in thrombotic thrombocytopenic purpura - current perspectives and new treatment strategies.

    PubMed

    Tersteeg, Claudia; Verhenne, Sebastien; Roose, Elien; Schelpe, An-Sofie; Deckmyn, Hans; De Meyer, Simon F; Vanhoorelbeke, Karen

    2016-02-01

    A deficiency in ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type-1 repeats, member 13) is associated with thrombotic thrombocytopenic purpura (TTP). Congenital TTP is caused by a defect in the ADAMTS13 gene resulting in decreased or absent enzyme activity; acquired TTP results from autoantibodies that either inhibit the activity or increase the clearance of ADAMTS13. Despite major progress in recent years in our understanding of the disease, many aspects around the pathophysiology of TTP are still unclear. Newer studies expanded the TTP field from ADAMTS13 and inhibitory antibodies to immune complexes, cloned autoantibodies, and a possible involvement of other proteases. Additionally, several new treatment strategies supplementing plasma-exchange and infusion are under investigation for a better and more specific treatment of TTP patients. In this review, we discuss the recent insights in TTP pathophysiology and describe upcoming therapeutic opportunities. PMID:26581428

  15. Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene.

    PubMed

    Krabbe, Johannes G; Kemna, Evelien W M; Strunk, Annuska L M; Jobse, Pieter A; Kramer, P A; Dikkeschei, L D; van den Heuvel, L P W J; Fijnheer, Rob; Verdonck, Leo F

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity. PMID:26267233

  16. Detection of platelet-binding anti-measles and anti-rubella virus IgG antibodies in infants with vaccine-induced thrombocytopenic purpura.

    PubMed

    Okazaki, Naho; Takeguchi, Masahiro; Sonoda, Kohji; Handa, Yohsuke; Kakiuchi, Tatsuo; Miyahara, Hiroaki; Akiyoshi, Kensuke; Korematsu, Seigo; Suenobu, Soichi; Izumi, Tatsuro

    2011-07-12

    A 15-month-old infant presented with thrombocytopenic purpura after sequential administration of measles-rubella combined vaccine, varicella vaccine and mumps vaccine every 4 weeks. Her thrombocytopenia persisted for more than 12 months. Both anti-measles and anti-rubella virus IgG antibodies were detected in the patient's-isolated platelets on day 154 of illness, which were not detected when there was a reduction of the serum IgG antibody titers on days 298 and 373 of illness, respectively.We also detected the isolated platelet-binding anti-measles and anti-rubella virus IgG antibodies in two other pediatric patients. This is the first report demonstrating direct evidence of vaccine-induced thrombocytopenic purpura. PMID:21539881

  17. A Case Report of an Elderly Woman With Thrombocytopenia and Bilateral Lung Infiltrates: A Rare Association Between Diffuse Alveolar Hemorrhage and Idiopathic Thrombocytopenic Purpura.

    PubMed

    Hashmi, Hafiz Rizwan Talib; Venkatram, Sindhaghatta; Diaz-Fuentes, Gilda

    2015-12-01

    Etiologies for diffuse alveolar hemorrhage are wide and range from infectious to vasculitis and malignant processes. Idiopathic thrombocytopenic purpura is an autoimmune disorder characterized by persistent thrombocytopenia, with a relatively indolent course in young patients, but a more complicated progression and high associated mortality in the older patients. Diffuse alveolar hemorrhage, complicating idiopathic thrombocytopenic purpura, is a very uncommon association, with only 2 reported cases in the literature. We present a 69-year-old healthy woman presenting with petechial rash, progressive dyspnea, and bilateral alveolar infiltrates. She was found to have idiopathic thrombocytopenic purpura associated with diffuse alveolar hemorrhage. The patient had an excellent response to high doses of pulse steroids and immunoglobulins.A high index of suspicion for noninfectious pulmonary diseases should be considered in patients with autoimmune diseases presenting with pulmonary infiltrates and hypoxia. Flexible bronchoscopy with sequential lavage is a relatively safe procedure in patients with coagulopathy and should be attempted to detect and confirm the diagnosis; absence of hemoptysis should not preclude the diagnosis. PMID:26683938

  18. 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

  19. Comparison of single port and three port laparoscopic splenectomy in patients with immune thrombocytopenic purpura: Clinical comparative study

    PubMed Central

    Barbaros, Umut; Aksakal, Nihat; Tukenmez, Mustafa; Agcaoglu, Orhan; Bostan, Mustafa Sami; Kilic, Berkay; Kalayci, Murat; Dinccag, Ahmet; Seven, Ridvan; Mercan, Selcuk

    2015-01-01

    AIM: Single-port laparoscopic surgery (SILS) has become increasingly popular during the last decades. This prospective study was undertaken to evaluate the feasibility of single-port laparoscopic splenectomy compared with conventional multiport laparoscopic splenectomy. MATERIALS AND METHODS: Between February 2, 2009 and August 29, 2011, a total of 40 patients with the diagnosis of immune thrombocytopenic purpura were included to study. Patients were alienated into two groups according to the procedure type including SILS and conventional multiport splenectomy. RESULTS: There were 19 patients in group 1, and 21 in group 2. Operative time was significantly shorter in group 1 versus group 2 (112.4 ± 13.56 vs 71.2 ±18.1 minutes, respectively, P < 0.05). One patient in group 1 had converted to laparatomy due to preoperative bleeding. Postoperative pain analyses (VAS Score) revealed superiority of SILS in the early post-operative days (P < 0.05). CONCLUSIONS: SILS splenectomy is a safe and effective alternative to standard laparoscopic splenectomy. PMID:26195874

  20. Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura

    PubMed Central

    Deford, Cassandra C.; Reese, Jessica A.; Schwartz, Lauren H.; Perdue, Jedidiah J.; Kremer Hovinga, Johanna A.; Lämmle, Bernhard; Terrell, Deirdra R.; Vesely, Sara K.

    2013-01-01

    Recovery from acute episodes of thrombotic thrombocytopenic purpura (TTP) appears complete except for minor cognitive abnormalities and risk for relapse. The Oklahoma TTP-HUS (hemolytic uremic syndrome) Registry enrolled 70 consecutive patients from 1995 to 2011 with ADAMTS13 activity <10% at their initial episode; 57 survived, with follow-up through 2012. The prevalence of body mass index (BMI), glomerular filtration rate (GFR), urine albumin/creatinine ratio (ACR), hypertension, major depression, systemic lupus erythematosus (SLE), and risk of death were compared with expected values based on the US reference population. At initial diagnosis, 57 survivors had a median age of 39 years; 45 (79%) were women; 21 (37%) were black; BMI and prevalence of SLE (7%) were greater (P < .001) than expected; prevalence of hypertension (19%; P = .463) was not different. GFR (P = .397) and ACR (P = .793) were not different from expected values. In 2011-2012, prevalence of hypertension (40% vs 23%; P = .013) and major depression (19% vs 6%; P = .005) was greater than expected values. Eleven patients (19%) have died, a proportion greater than expected compared with US and Oklahoma reference populations (P < .05). TTP survivors may have greater risk for poor health and premature death. PMID:23838348

  1. Methylene blue-photoinactivated plasma versus quarantine fresh frozen plasma in thrombotic thrombocytopenic purpura: a multicentric, prospective cohort study.

    PubMed

    del Río-Garma, Julio; Alvarez-Larrán, Alberto; Martínez, Clara; Muncunill, Josep; Castellà, Dolors; de la Rubia, Javier; Zamora, Concepción; Corral, Mercedes; Viejo, Aurora; Peña, Francisco; Rodríguez-Vicente, Pilar; Contreras, Enric; Arbona, Cristina; Ramírez, Consuelo; Garcia-Erce, José A; Alegre, Adrián; Mateo, José; Pereira, Arturo

    2008-10-01

    Plasma exchange (PE) with plasma infusion is the treatment of choice for thrombotic thrombocytopenic purpura (TTP) but doubts remain as to whether all kinds of plasma are equally effective. A multicentric cohort study was conducted to compare methylene blue-photoinactivated plasma (MBPIP) with quarantine fresh frozen plasma (qFFP) in the treatment of TTP. One hundred and two episodes of idiopathic TTP were included; MBPIP was used in 63 and qFFP in 39. The treatment schedule consisted of daily PE and costicosteroids, and the main end-point was remission status on day 8. Patients treated with MBPIP required more PEs (median: 11 vs. 5, P = 0.002) and a larger volume of plasma (median: 485 ml/kg vs. 216 ml/kg, P = 0.007) to achieve a remission, and presented more recrudescences while on PE therapy (29 of 63 vs. 8 of 39, P = 0.02) than those receiving qFFP. After adjustment for possible confounding factors, the use of MBPIP was associated with a lower likelihood of remission on day 8 [Odds ratio (OR): 0.17; 95% confidence interval (CI): 0.06-0.47] and a higher risk of recrudescence while on treatment (OR: 4.2; 95% CI: 1.6-10.8). In conclusion, MBPIP is less effective than qFFP in the treatment of TTP. PMID:18637799

  2. 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. PMID:26052230

  3. The Oklahoma Thrombotic Thrombocytopenic Purpura-haemolytic Uraemic Syndrome Registry. A model for clinical research, education and patient care.

    PubMed

    George, J N; Vesely, S K; Terrell, D R; Deford, C C; Reese, J A; Al-Nouri, Z L; Stewart, L M; Lu, K H; Muthurajah, D S

    2013-05-29

    The Oklahoma Thrombotic Thrombocytopenic Purpura-Haemolytic Uraemic Syndrome (TTP-HUS) Registry has a 24 year record of success for collaborative clinical research, education, and patient care. This article tells the story of how the Registry began and it describes the Registry's structure and function. The Registry provides a model for using a cohort of consecutive patients to investigate a rare disorder. Collaboration between Oklahoma, United States and Bern, Switzerland has been the basis for successful interpretation of Registry data. Registry data have provided new insights into the evaluation and management of TTP. Because recovery from acute episodes of TTP has been assumed to be complete, the increased prevalence of hypertension, diabetes, depression, and death documented by long-term follow-up was unexpected. Registry data have provided opportunities for projects for students and trainees, education of physicians and nurses, and also for patients themselves. During our follow-up, patients have also educated Registry investigators about problems that persist after recovery from an acute episode of TTP. Most important, Registry data have resulted in important improvements for patient care. PMID:23364684

  4. Sporadic bloody diarrhoea-associated thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome: an adult and paediatric comparison.

    PubMed

    Karpac, Charity A; Li, Xiaoning; Terrell, Deirdra R; Kremer Hovinga, Johanna A; Lämmle, Bernhard; Vesely, Sara K; George, James N

    2008-05-01

    Although diarrhoea-associated haemolytic uremic syndrome (HUS) in children is well described, the clinical features of bloody diarrhoea-associated thrombotic thrombocytopenic purpura (TTP)-HUS in adults are not documented. Twenty-one adults, 6.5% of the 322 adults in The Oklahoma TTP-HUS Registry, 1989-2006, have presented with bloody diarrhoea. There were no case clusters. Escherichia coli O157:H7 was identified in five patients, but many patients did not have appropriate studies. The annual incidence was 0.68/10(6), 10-fold less than the incidence of diarrhoea-associated HUS in children in Oklahoma. Two (13%) of 16 patients in whom ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) was measured had <10% activity. Severe neurological abnormalities (67%) and renal failure (62%) were common; seven patients (33%) died; no survivors have relapsed. Compared to the 38 other Oklahoma Registry patients with ADAMTS13 <10%, frequency of severe neurological abnormalities and death was not different; frequency of renal failure was greater; frequency of relapse was less. Compared to 5999 children with sporadic diarrhoea-associated HUS in published reports, frequency of renal failure and relapse was not different; frequency of severe neurological abnormalities and death was greater (P < 0.05 for all differences). Awareness of the continuous occurrence of sporadic bloody diarrhoea-associated TTP-HUS in adults is important for prompt diagnosis and appropriate management. PMID:18422775

  5. Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura.

    PubMed

    Deford, Cassandra C; Reese, Jessica A; Schwartz, Lauren H; Perdue, Jedidiah J; Kremer Hovinga, Johanna A; Lämmle, Bernhard; Terrell, Deirdra R; Vesely, Sara K; George, James N

    2013-09-19

    Recovery from acute episodes of thrombotic thrombocytopenic purpura (TTP) appears complete except for minor cognitive abnormalities and risk for relapse. The Oklahoma TTP-HUS (hemolytic uremic syndrome) Registry enrolled 70 consecutive patients from 1995 to 2011 with ADAMTS13 activity <10% at their initial episode; 57 survived, with follow-up through 2012. The prevalence of body mass index (BMI), glomerular filtration rate (GFR), urine albumin/creatinine ratio (ACR), hypertension, major depression, systemic lupus erythematosus (SLE), and risk of death were compared with expected values based on the US reference population. At initial diagnosis, 57 survivors had a median age of 39 years; 45 (79%) were women; 21 (37%) were black; BMI and prevalence of SLE (7%) were greater (P < .001) than expected; prevalence of hypertension (19%; P = .463) was not different. GFR (P = .397) and ACR (P = .793) were not different from expected values. In 2011-2012, prevalence of hypertension (40% vs 23%; P = .013) and major depression (19% vs 6%; P = .005) was greater than expected values. Eleven patients (19%) have died, a proportion greater than expected compared with US and Oklahoma reference populations (P < .05). TTP survivors may have greater risk for poor health and premature death. PMID:23838348

  6. Congenital thrombotic thrombocytopenic purpura: Upshaw-Schulman syndrome: a cause of neonatal death and review of literature.

    PubMed

    Sharma, Deepak; Shastri, Sweta; Pandita, Aakash; Sharma, Pradeep

    2016-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare disorder in children characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. The classic Moschcowitz Pentads of TTP include hemolytic anemia, with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decrease renal function and fever. We report a newborn who was diagnosed with congenital TTP. The newborn was admitted at age of 40 h, in our hospital, in view of respiratory distress with impending respiratory failure and red colored urine. On examination, the newborn was febrile, tachypneic, had deep icterus, pallor and no hepatosplenomegaly. Family history was significant with one unexplained neonatal death at age of 24 with symptoms of red colored urine. Examination of peripheral smear was diagnostic with the presence of fragmented RBCS, giant but fewer platelets consistent with a diagnosis of MAHA. The diagnosis of TTP was confirmed with low ADAMTS activity and gene analysis showed c 2203 G > T-p.Glu735X (domain TSP1-2) mutation in exon 18 of ADAMTS 13 gene. The newborn had rapid deterioration, with respiratory distress and refractory shock leading to death. Post-mortem bone marrow done showed marrow hyperplasia. PMID:26365135

  7. Primary Percutaneous Coronary Intervention by a Stentless Technique for Acute Myocardial Infarction with Idiopathic Thrombocytopenic Purpura: A Case Report and Review of the Literature.

    PubMed

    Fujino, Susumu; Niwa, Satoru; Fujioka, Kensuke; Mabuchi, Tomohito; Noji, Yoshihiro; Yamaguchi, Masato; Aoyama, Takahiko

    2016-01-01

    A 78-year-old man who had been diagnosed with idiopathic thrombocytopenic purpura (ITP) was admitted to our hospital with chest pain, cold sweating and nausea. An electrocardiogram and echocardiogram revealed an ST elevated acute lateral myocardial infarction. He underwent an immediate cardiac catheterization. An occluded left circumflex artery was detected by coronary angiography. Reperfusion was performed successfully by non-slip element balloon angioplasty alone, without stenting, to avoid prolonged dual anti-platelet therapy. In this report we discussed the management strategies of acute myocardial infarction in a patient with concomitant ITP. PMID:26781014

  8. CD4+ T cells from patients with acquired thrombotic thrombocytopenic purpura recognize CUB2 domain-derived peptides.

    PubMed

    Verbij, Fabian C; Turksma, Annelies W; de Heij, Femke; Kaijen, Paul; Lardy, Neubury; Fijnheer, Rob; Sorvillo, Nicoletta; Ten Brinke, Anja; Voorberg, Jan

    2016-03-24

    Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder resulting from the development of autoantibodies against ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). HLA-DRB1*11 provides a risk factor for developing acquired TTP. Pulsing of antigen-presenting cells from HLA-DRB1*11- and HLA-DRB1*03-positive individuals with ADAMTS13 resulted in presentation of peptides derived from the CUB2 domain of ADAMTS13 with core sequences FINVAPHAR or ASYILIRD. Here, we assessed whether FINVAPHAR- or ASYILIRD-reactive CD4(+)T cells are present in peripheral blood mononuclear cells from HLA-DRB1*11 and HLA-DRB1*03-positive subjects with acquired TTP. The presence of ADAMTS13-reactive CD4(+)T cells was addressed by flow cytometry and the expression of activation marker CD40 ligand by CD4(+)T cells. FINVAPHAR-reactive CD4(+)T cells were identified in an HLA-DRB1*11-positive patient during the acute phase of the disease whereas ASYILIRD-positive CD4(+)T cells were identified in a DRB1*03-positive patient with acquired TTP. Frequencies of CUB2 domain-reactive CD4(+)T cells ranged from 3.3% to 4.5%. Control peptides in which the anchor residues were modified did not induce activation of CD4(+)T cells. Taken together, our data provide evidence for the involvement of CUB2 domain-reactive CD4(+)T cells in the etiology of acquired TTP. PMID:26747250

  9. 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

  10. Newly diagnosed versus relapsed idiopathic thrombotic thrombocytopenic purpura: a comparison of presenting clinical characteristics and response to treatment.

    PubMed

    Alvarez-Larrán, Alberto; del Río-Garma, Julio; Pujol, Misericòrdia; de la Rubia, Javier; Hernández-Jodra, Manuel; Borrell, Montserrat; González-Porras, José R; García-Gala, José M; Viejo, Aurora; Enríquez, Lourdes; Arbona, Cristina; García-Erce, José A; Noblejas, Ana G; Pereira, Arturo

    2009-10-01

    The remission rate with plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) exceeds 80%, but the disease relapses in up to 20-30% of the cases. Clinical characteristics and response to treatment of relapsed TTP are not well defined. The objective of the present study was to compare the clinical and biological characteristics at presentation and the response to treatment between de novo and relapsed TTP. For such purpose, a total of 102 episodes of idiopathic TTP (70 de novo and 32 relapses) included in a recent multicentric prospective cohort study were analysed. All patients were homogeneously treated with daily PE and costicosteroids. In comparison with de novo TTP, episodes of relapsed TTP showed a higher Hb level (median, 122 g/l versus 91 g/l, p < 0.001) and lower serum lactate dehydrogenase (2.2- versus 4.5-fold above the upper limit of normality, p < 0.001). Neurological symptoms and fever were less frequently observed in patients with relapsed TTP than in patients with de novo TTP. Patients with relapsed TTP needed fewer PE sessions (five versus ten, p = 0.02) and a smaller volume of plasma (221 ml/kg versus 468 ml/kg, p = 0.004) to achieve remission than those with de novo TTP. There was no significant difference in the rate of recrudescence under treatment, the need of complementary treatments or the frequency of refractoriness to PE therapy. In conclusion, relapsed TTP has a milder clinical profile and responds more easily to PE than de novo TTP. PMID:19205654

  11. 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

  12. T lymphocytes from autoimmune thrombocytopenic purpura show a defective activation and proliferation after cytoplasmic membrane and intracytoplasmic mitogenic signals.

    PubMed

    Garcia-Suarez, J; Prieto, A; Manzano, L; Reyes, E; Molto, L; Alvarez-Mon, M

    1993-09-01

    T lymphocyte activation and proliferation are complex cellular processes involving membrane and cytoplasmatic molecules as well as the secretion and response to cytokines, mainly interleukin 2. There is increasing evidence that autoimmune thrombocytopenic purpura (ATP) is associated with an alteration of the regulation of the immune system. The blastogenic response of purified T lymphocytes to mitogens that interact with membrane molecules (phytohemaglutinin, anti-CD3 monoclonal antibody) and with intracytoplasmic protein kinase C (phorbol myristate acetate) has been investigated in 22 ATP patients and 18 healthy controls. After the signal given by the three different mitogens [3H]-thymidine uptake in T lymphocytes from ATP patients was found to be significantly decreased with respect to that found in healthy controls under similar experimental conditions (P < 0.05). Analysis of the cell cycle progression in these T lymphocytes from ATP patients, showed a significantly diminished percentage of cells in S-phase after PHA stimulation (P < 0.05). The percentage of CD3+ cells in the CD2+ lymphocyte preparations was significantly decreased in ATP patients relative to healthy controls (P < 0.05). But there was no significant correlation between this percentage and the blastogenic response to PHA in the CD2+ cellular preparations from both groups of subjects. No significant differences were found in the percentages of CD4+ and CD8+ cells. These data indicate that the impaired blastogenic response of T lymphocytes from ATP patients may be ascribed to an intrinsic defect in these T cells. This defective proliferative response of T lymphocytes from ATP patients cannot be ascribed to either defective interleukin 2 production or receptor expression which were both similar to those of healthy controls (P > 0.05). And, the presence of saturating amounts of exogenous interleukin 2 did not normalize the defective proliferative response the mitogenic signals on the part of T lymphocytes from ATP patients. We conclude that T lymphocytes from ATP patients have a defective proliferative response to membrane and intracytoplasmatic mitogenic signals. PMID:8393613

  13. Re-Examination of 30-Day Survival and Relapse Rates in Patients with Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome

    PubMed Central

    Bittencourt, Cassiana E.; Ha, Jennifer P.; Maitta, Robert W.

    2015-01-01

    Background and Objectives Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are characterized by microangiopathic hemolytic anemia and thrombocytopenia. Interestingly, markedly different survival rates have been reported despite increases in survivability. We studied TTP-HUS 30-day mortality and relapse rates of patients who received TPE at our institution and compared them to published data. Patients and Methods Retrospective study analyzed 30-day mortality and relapse rates attributed to TTP-HUS from 01/01/2008 to 12/31/2012 and compared them to comparable literature reporting mortality and survival. Studies describing other etiologies for TPE and different mortality time interval were excluded. Results Fifty-nine patients were analyzed and all were initially treated with TPE and corticosteroids. Eleven patients were classified as not having TTP-HUS due to testing or clinical reassessment which ruled in other etiologies, and 18/59 patients had ADAMTS13 activity <10%. Of remaining patients, 36/48 (75%) were diagnosed as idiopathic and 12/48 (25%) as secondary TTP-HUS. Patients received a mean of 12 TPEs (range 1-42); 42/48 (87.5%) patients had ADAMTS13 activity measured; complete response obtained in 39/48 (81.2%) patients (platelet count >100 x 109/L); partial response in 4/48 (8%); and 5/48 (10.4%) did not have increases in platelet counts (2/5 of these patients died within the study period). Forty percent of patients obtained platelet counts >150 x 109/L. Overall 30-day mortality for our patient cohort was 6.7% (4/59). Comparison of our mortality rate to combined data of five published studies of 16% (92/571) showed a significant difference, p = 0.04. Our relapse rate was 18.6% (11/59) similar to previous reports. Conclusions Wide differences in mortality may be due to grouping of two distinct pathologic entities under TTP-HUS; and presence of confounding factors in the patient populations under study such as co-morbidities, promptness of TPE initiation, delay in diagnosis and therapeutic practice. PMID:26000799

  14. [A Case of Thrombotic Thrombocytopenic Purpura in a Patient Undergoing FOLFOX6 plus Panitumumab Therapy for Unresectable Recurrent Rectal Cancer with a Rapidly Progressive Course].

    PubMed

    Kato, Kuniyuki; Michishita, Yoshihiro; Oyama, Kenichi; Hatano, Yoshiaki; Nozawa, Tatsuru; Ishibashi, Masahisa; Konda, Ryuichiro; Sasaki, Akira

    2016-01-01

    A 71-year-old male patient began FOLFOX6 plus panitumumab treatment for unresectable recurrent rectal cancer. He developed thrombocytopenia after 2 courses of treatment and therefore a platelet transfusion was performed. The day after transfusion, the patient developed jaundice and hematuria. His lactate dehydrogenase levels had increased and a peripheral blood smear review revealed the presence of schistocytes. Anti-ADAMTS13 antibodies were present, and there was a reduction in ADAMTS13 activity. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with a plasma exchange. The day after the plasma exchange, his clinical condition rapidly worsened and he died. Thrombocytopenia due to chemotherapy often appears as myelosuppression. If conditions such as jaundice, indirect bilirubinemia, or hematuria appear during the course of chemotherapy, this condition must be considered as a differential diagnosis. PMID:26809542

  15. Idiopathic thrombocytopenic purpura (ITP)

    MedlinePLUS

    ... bleeding disorder in which the immune system destroys platelets, which are necessary for normal blood clotting. Persons with the disease have too few platelets in the blood. ITP is sometimes called immune ...

  16. Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr-labeled platelets differ

    SciTech Connect

    Heyns A du, P.; Badenhorst, P.N.; Loetter, M.G.P.; Pieters, H.; Wessels, P.; Kotze, H.F.

    1986-01-01

    Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr-labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

  17. 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.

  18. Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura

    SciTech Connect

    Gangarossa, S.; Mattina, T.; Romano, V.; Milana, G.; Mollica, F.; Schiliro, G.

    1996-03-15

    Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient. 23 refs., 2 figs., 1 tab.

  19. Long-term remission induced by low-dose rituximab for relapsed and refractory thrombotic thrombocytopenic purpura: A report of two cases

    PubMed Central

    TONG, HONG-YAN; YE, LI; YE, XING-NONG; LU, DE-MIN; LI, YING

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is acquired in the majority of cases. Traditional therapy consists of plasma exchange (PEX), as well as the administration of certain immunosuppressive agents including steroids. A standard dose of rituximab (RTX) at 375 mg/m2 weekly for 4 consecutive weeks was recently demonstrated to have significant activity in patients with acquired TTP. To date, clinicians have limited experience using low-dose RTX. In the present study, 2 patients were treated with low-dose RTX at 100 mg weekly for 4 consecutive weeks as a salvage therapy following failure to respond to PEX and other immunosuppressive agents. Prior to RTX therapy, the patients had severely deficient ADAMTS13 activity and detectable anti-ADAMTS13 inhibitors. The patients achieved complete remission and presented long-term stabilization during follow-up. Repeated detection during follow-up demonstrated that the patients had 100% ADAMTS13 activity and undetectable anti-ADAMTS13 antibodies. Although further investigation in a prospective clinical trial is required, the use of low-dose RTX seems to be as effective as a standard dose for patients with relapsing or refractory acquired TTP. PMID:26668631

  20. Initial Experience with the Use of Thrombopoetin Receptor Agonists in Patients with Refractory HIV-Associated Immune Thrombocytopenic Purpura: A Case Series.

    PubMed

    Kowalczyk, Mark; Rubinstein, Paul G; Aboulafia, David M

    2015-01-01

    HIV-associated immune thrombocytopenic purpura (ITP) has decreased in incidence 10-fold since the advent of highly active antiretroviral therapy (HAART). For patients with detectable HIV viral loads, first-line treatment approaches involve optimizing HAART followed by standard ITP options used to treat those without HIV infection. In the general population, the thrombopoetin receptor agonists (TRAs), eltrombopag and romiplostim, are effective when used as salvage ITP therapy. In addition, eltrombopag has been used effectively in patients with thrombocytopenia secondary to hepatitis C--a virus seen commonly in HIV-infected patients, especially in those who also have a history of intravenous drug use. There are, however, few reports or studies of TRAs use in those with HIV infection. Herein, we describe 5 cases of refractory HIV-associated ITP managed with TRAs. Although platelet counts improved for all patients, 2 patients succumbed to thromboembolic complications. Our initial experience, as well as our findings from a Medline review, supports the potential utility of TRA as salvage therapy in the treatment of HIV-related ITP; however, we recommend caution in the use of these agents in those who are at highest risk of thrombosis. Additional studies are needed to determine the efficacy and, more importantly, the safety of TRAs in treatment of HIV-associated ITP. PMID:25504472

  1. Dieulafoy Lesion in the Ascending Colon Presenting with Gastrointestinal Bleeding and Severe Anemia Complicated by a Coexisting Severe Resistant Chronic Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Eltawansy, Sherif Ali; Thyagarajan, Brag; Baig, Nadeem

    2014-01-01

    Background. GI (gastrointestinal) bleeding can be due to a variety of etiologies ranging from being common like bleeding peptic ulcer disease or esophageal varices. One of the rarely documented causes is the Dieulafoy lesion which is known as an abnormally large ectatic artery that penetrates the gut wall, occasionally eroding through the mucosa causing massive bleeding. In addition to that, we refer to the uncommon presentation of Dieulafoy lesion itself as it is well known to be found in the stomach, esophagus, duodenum, and jejunum but not the ascending colon as in our case. The patient had a coexisting ITP (idiopathic thrombocytopenic purpura) that was resistant to different therapies. Case Report. We report a case of a 48-year-old Egyptian female known for chronic ITP resistant to treatment. The patient presented with bright red bleeding per rectum and severe life threatening anemia. Endoscopic study showed a Dieulafoy lesion. Endoscopic clipping was successful in controlling the bleeding. Conclusion. Dieulafoy lesion is a rare reason for GI bleeding and can present in common or unexpected places. Also extreme caution should be used in patients with bleeding tendency due to different reasons, like ITP in our case. PMID:25405040

  2. The comparison of perceived stress in idiopathic thrombocytopenic purpura patients referred to Seyed Al-Shohada Hospital with healthy people in Isfahan, Iran, 2013

    PubMed Central

    Hemati, Zeinab; Kiani, Davood

    2015-01-01

    Background: Mental stress and daily crises comprise a part of physical and mental threats. Perceived stress is a physical and mental threat, as well. Perceived stress is a psychological process during which the individual considers his/ her physical and psychological welfare as being threatened. Since idiopathic thrombocytopenic purpura (ITP) is one of the chronic diseases being able to affect patients' perceived stress, this study was conducted to compare perceived stress in ITP patients and healthy people. Materials and Methods: This is a descriptive-comparative study with control and case groups. In this study, 64 ITP patients referring Seyed Al-Shohada Hospital and the same number of healthy individuals from the patients' neighborhood, as the control group, were selected randomly and compared. The Kohen Perceived Stress Standard Questionnaire was used to collect the data. The data were analyzed by SPSS and Student’s independent t-test, chi-square, and Mann-Whitney test. Results : 64.1%, 59.4% and 53.1% of participants in case group were older than 35 years old, female and had elementary education. 78.1% of case group had severe perceived stress. 70.3% of participants in control group experienced mild perceived stress. Mann-Whitney test showed significant difference between two groups in level of stress (p<0.001). Conclusion: In ITP patients, perceived stress was considerable. Planning interventional measures to determine stress-making agents and subside or at least control them is very essential. PMID:25922646

  3. 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

  4. Long-term follow-up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis.

    PubMed

    Bourgeois, Emmanuelle; Caulier, Marie T; Delarozee, Catherine; Brouillard, Marc; Bauters, Francis; Fenaux, Pierre

    2003-03-01

    Splenectomy remains the most effective treatment of chronic autoimmune idiopathic thrombocytopenia (ITP) (i.e. of > 6 months duration). Treatment of patients refractory to splenectomy (with absence of response or relapse after initial response) is difficult, and their long-term outcome is not well known. Over a 10-year period, 183 patients with chronic ITP were splenectomized including 158 adults and 25 children ( 100 x 10(9)/l, nine of them without treatment and 27 of them with low-dose steroids or azathioprine; six (13%) remained moderately thrombocytopenic (35 x 10(9)/l to 100 x 10(9)/l platelets); the last five patients, without response to any treatment (up to six regimens), remained severely thrombocytopenic (platelets < 20 x 10(9)/l), and three of them died from bleeding. Twenty-seven (57%) of the 47 refractory cases required at least one hospitalization, in the majority of cases for intravenous immunoglobulin (IVIg) infusions. Seven of the refractory cases occurred in children. Six of them subsequently reached platelet counts > 100 x 10(9)/l, but one died from bleeding. Our findings confirm the overall favourable long-term prognosis of chronic ITP refractory to splenectomy. PMID:12648082

  5. The complex differential diagnosis between thrombotic thrombocytopenic purpura and the atypical hemolytic uremic syndrome: Laboratory weapons and their impact on treatment choice and monitoring.

    PubMed

    Mannucci, P M; Cugno, M

    2015-11-01

    Thrombocytopenia and microangiopathic hemolytic anemia are the hallmark of the thrombotic microangiopathies (TMAs) thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP, inherited or autoimmune, is mainly caused by the plasma deficiency of the von Willebrand factor cleaving protease ADAMTS13, owing to gene mutations or autoantibodies. Typical HUS is often caused by infections with Shiga-Toxin-producing Escherichia coli and thus is called STEC-HUS. The rarer atypical form of HUS is often associated with complement dysregulation, owing to the inherited deficiency or dysfunction of factor H or other complement proteins. In the past the distinction between these TMAs was almost exclusively based on clinical grounds, the term TTP being used for cases with predominant neurological involvement, STEC HUS for cases presenting with bloody diarrhea and atypical HUS identifying patients with severe renal damage. However the clinical presentation may not easily distinguish TTP from atypical HUS. A more accurate differential diagnosis has clinical implications, because plasma exchange (the treatment of choice in TTP) is much less effective in atypical HUS, which shows dramatic short- and long-term therapeutic benefits from eculizumab, a monoclonal antibody that inhibits complement activation. This article will point out that the measurement of ADAMTS13 is able to diagnose accurately the majority of TTP cases, and that very simple tests such as the platelet count and serum creatinine can predict the deficiency of the protease with a good degree of accuracy. In atypical HUS, new methods were recently developed that not only demonstrate the activation of the complement system, i.e., the main disease mechanism, but also help to tailor the short- and long-term treatment with eculizumab. PMID:26386489

  6. Effect of rituximab on B cell phenotype and serum B cell-activating factor levels in patients with thrombotic thrombocytopenic purpura

    PubMed Central

    Becerra, E; Scully, M A; Leandro, M J; Heelas, E O; Westwood, J-P; De La Torre, I; Cambridge, G

    2015-01-01

    Autoantibodies inhibiting the activity of the metalloproteinase, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), underlie the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Rituximab (RTX) combined with plasma-exchange (PEX) is an effective treatment in TTP. Patients can remain in remission for extended periods following PEX/RTX, and this is associated with continuing reduction in antibodies to ADAMTS13. Factors controlling B cell differentiation to autoantibody production, including stimulation through the B cell receptor and interactions with the B cell-activating factor (BAFF), may thus impact length of remission. In this cross-sectional study, we measured naive and memory B cell phenotypes [using CD19/immunoglobulin (Ig)D/CD27] following PEX/RTX treatment in TTP patients at B cell return (n?=?6) and in 12 patients in remission 10–68 months post-RTX. We also investigated relationships among serum BAFF, soluble CD23 (sCD23– a surrogate measure of acquiring B memory (CD27+) phenotype) and BAFF receptor (BAFF-R) expression. At B cell return after PEX/RTX, naive B cells predominated and BAFF-R expression was reduced compared to healthy controls (P?

  7. Presence of Antiphospholipid Antibodies as a Risk Factor for Thrombotic Events in Patients with Connective Tissue Diseases and Idiopathic Thrombocytopenic Purpura.

    PubMed

    Habe, Koji; Wada, Hideo; Matsumoto, Takeshi; Ohishi, Kohshi; Ikejiri, Makoto; Matsubara, Kimiko; Morioka, Tatsuhiko; Kamimoto, Yuki; Ikeda, Tomoaki; Katayama, Naoyuki; Mizutani, Hitoshi

    2016-01-01

    Objective Antiphospholipid syndrome (APS) is a well-known complication of habitual abortion and/or thrombosis and is frequently associated with autoimmune diseases. Methods We retrospectively investigated the relationships between the presence of antiphospholipid antibodies (aPLs) and the incidence of thrombotic events (THEs) in 147 patients with various connective tissue diseases (CTD) suspected of having APS and 86 patients with idiopathic thrombocytopenic purpura (ITP). THEs were observed in 41 patients, including 14 cases of venous thrombosis, 21 cases of arterial thrombosis and eight cases of complications of pregnancy. Results The prevalence of THE was significantly high in the systemic lupus erythematosus (SLE) patients compared with the other CTD patients and ITP patients. The frequency of lupus anticoagulant (LA), anticardiolipin antibodies (aCL)-β2-glycoprotein (GPI) complex IgG and aPL was significantly high in the SLE patients compared with the ITP patients. Subsequently, the rate of development of THE was significantly high in the patients with aPLs. In particular, the incidence of THE was significantly high in the SLE or ITP patients with LA, aCL-β2GPI IgG or aPL. The optimal cut-off values for LA, aCL IgG and aCL-β2GPI complex IgG for the risk of THEs were higher in the SLE patients in comparison to the values obtained when using the kit provided by the manufacturer. Conclusion Although aPLs is frequently associated with SLE and is a causative factor for thrombosis, the optimal cut-off value for aPL for predicting the occurrence of THEs varies among different underlying diseases. PMID:26984073

  8. The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura. A clinical, biochemical and in silico study.

    PubMed

    Lancellotti, Stefano; Peyvandi, Flora; Pagliari, Maria Teresa; Cairo, Andrea; Abdel-Azeim, Safwat; Chermak, Edrisse; Lazzareschi, Ilaria; Mastrangelo, Stefano; Cavallo, Luigi; Oliva, Romina; De Cristofaro, Raimondo

    2015-12-22

    Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (

  9. A disease-specific measure of health-related quality of life for use in adults with immune thrombocytopenic purpura: Its development and validation

    PubMed Central

    Mathias, Susan D; Bussel, James B; George, James N; McMillan, Robert; Okano, Gary J; Nichol, Janet L

    2007-01-01

    Background No validated disease-specific measures are available to assess health-related quality of life (HRQoL) in adult subjects with immune thrombocytopenic purpura (ITP). Therefore, we sought to develop and validate the ITP-Patient Assessment Questionnaire (ITP-PAQ) for adult subjects with ITP. Methods Information from literature reviews, focus groups with subjects, and clinicians were used to develop 50 ITP-PAQ items. Factor analyses were conducted to develop the scale structure and reduce the number of items. The final 44-item ITP-PAQ, which includes ten scales [Symptoms (S), Bother-Physical Health (B), Fatigue/Sleep (FT), Activity (A), Fear (FR), Psychological Health (PH), Work (W), Social Activity (SA), Women's Reproductive Health (RH), and Overall (QoL)], was self-administered to adult ITP subjects at baseline and 7–10 days later. Test-retest reliability, internal consistency reliability, construct and known groups validity of the final ITP-PAQ were evaluated. Results Seventy-three subjects with ITP completed the questionnaire twice. Test-retest reliability, as measured by the intra-class correlation, ranged from 0.52–0.90. Internal consistency reliability was demonstrated with Cronbach's alpha for all scales above the acceptable level of 0.70 (range: 0.71–0.92), except for RH (0.66). Construct validity, assessed by correlating ITP-PAQ scales with established measures (Short Form-36 v.1, SF-36 and Center for Epidemiologic Studies Depression Scale, CES-D), was demonstrated through moderate correlations between the ITP-PAQ SA and SF-36 Social Function scales (r = 0.67), and between ITP-PAQ PH and SF-36 Mental Health Scales (r = 0.63). Moderate to strong inter-scale correlations were reported between ITP-PAQ scales and the CES-D, except for the RH scale. Known groups validity was evaluated by comparing mean scores for groups that differed clinically. Statistically significant differences (p < 0.01) were observed when subjects were categorized by treatment status [S, FT, B, A, PH, and QoL, perceived effectiveness of ITP treatment [S], and time elapsed since ITP diagnosis [PH]. Conclusion Results provide preliminary evidence of the reliability and validity of the ITP-PAQ in adult subjects with ITP. Further work should be conducted to assess the responsiveness and to estimate the minimal clinical important difference of the ITP-PAQ to more fully understand the impact of ITP and its treatments on HRQoL. PMID:17316442

  10. What Causes Thrombotic Thrombocytopenic Purpura?

    MedlinePLUS

    ... Tests Blood and Marrow Stem Cell Transplant Excessive Blood Clotting Hemolytic Anemia Send a link to NHLBI to ... gene controls the enzyme, which is involved in blood clotting. Not having enough enzyme activity causes overactive blood ...

  11. How Is Thrombotic Thrombocytopenic Purpura Diagnosed?

    MedlinePLUS

    ... blood product that's normally removed by the kidneys. Coombs Test This blood test is used to find ... TTP is the cause of hemolytic anemia, the Coombs test is negative. The test is positive if ...

  12. Genetics Home Reference: Thrombotic thrombocytopenic purpura

    MedlinePLUS

    ... that is involved in the normal process of blood clotting. Mutations in this gene lead to a severe ... as pregnancy, surgery, and infection may trigger abnormal blood clotting and its associated complications. Read more about the ...

  13. 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 ...

  14. Progressive Pigmentary Purpura

    MedlinePLUS

    ... Rights Job Postings Sections of the JAOCD JAOCD Archive Published Members Online Dermatology Journals Edit This Favorite Name: Category: Share: Yes No, Keep Private Progressive Pigmentary Purpura Share | Progressive pigmentary purpura (we ...

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

    ClinicalTrials.gov

    2016-01-13

    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

  16. The clinical implications of adult-onset henoch-schonelin purpura

    PubMed Central

    2011-01-01

    Henoch-Schonlein 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. Pathologically, it can be considered a form of immune complex-mediated leukocytoclastic vasculitis (LCV) involving the skin and other organs. Though it primarily affects children (over 90% of cases), the occurrence in adults has been rarely reported. Management often involves the use of immunomodulatory or immune-suppressive regimens. PMID:21619657

  17. Local leukocyte proliferation as a target for cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis grade VI.

    PubMed

    Kaneko, Masahiro; Ikezumi, Yohei; Yamada, Takeshi; Hasegawa, Hiroya; Kaneko, Utako; Saitoh, Akihiko

    2016-01-01

    Henoch-Schönlein purpura nephritis (HSPN) is one of the most common types of chronic glomerulonephritis in children; however, there have been few reports on the pathogenesis and management of grade VI HSPN. We present the case of a 6-year-old boy with grade VI HSPN accompanied by severe nephrotic syndrome and hypocomplementaemia. Immunohistological studies revealed profound glomerular accumulation of CD45- and CD68-positive inflammatory cells. Moreover, some cells expressed the proliferating marker proliferating cell nuclear antigen. His proteinuria and general oedema persisted despite repeated high-dose steroid therapy; however, these clinical symptoms immediately improved after beginning treatment with cyclophosphamide (CyP). Grade VI HSPN was successfully treated with steroids and immunosuppressants. Among immunosuppressive drugs, CyP was considered the most effective. PMID:26693846

  18. Henoch Schonlein purpura associated with bee sting: case report.

    PubMed

    Gálvez-Olortegui, José; Álvarez-Vargas, Mayita; Durand-Vergara, Juan; Díaz-Lozano, Marisol; Gálvez-Olortegui, Tomas; Armas-Ramírez, Indira; Hilario-Vargas, Julio

    2015-01-01

    Henoch Schonlein purpura (HSP) is a common childhood vasculitis, characterized by a non-thrombocytopenic palpable purpura and systemic features. It can be triggered by conditions like infections and insect bites. We present the case of a six-year-old girl with palpable maculopapular lesions on the lower limbs, itching, mild pain, swelling of feet, limitation of limb mobility, and a history of bee sting. Thigh skin biopsy was performed, with a report of leucocytoclastic vasculitis, and was diagnosed as HSP. She was prescribed bed rest, and was given oral hydration. The patient outcome was favorable and was discharged after five days. This is the fifth report of a HSP case associated with a bee sting with an uncomplicated course, which is in contrast to previous case reports. PMID:26610057

  19. Safety and Efficacy Study of Romiplostim (AMG 531) to Treat ITP in Pediatric Subjects

    ClinicalTrials.gov

    2014-07-18

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

  20. Henoch-Schönlein purpura

    MedlinePLUS

    Leukocytoclastic vasculitis; Anaphylactoid purpura; Vascular purpura ... Ardoin SP, Fels E. Vasculitis syndromes. In: Kliegman RM, Stanton B, St. Geme J, Schor N, Behrman RE, eds. Nelson Textbook of Pediatrics . 19th ed. ...

  1. Erythropoietic protoporphyria showing solar purpura.

    PubMed

    Torinuki, W; Miura, T

    1983-01-01

    An 11-year-old girl with erythropoietic protoporphyria is described. She was admitted to our hospital complaining of swelling and purpura on her arms resulting from overexposure to solar radiation. An elevated level of protoporphyrin in the red blood cells and feces was detected by thin-layer chromatography and fluorescent scanning analysis. PMID:6642040

  2. Purpura fulminans with haemolytic anaemia

    PubMed Central

    Nagi, N. A.; Al-Hasso, A. R. A.

    1974-01-01

    A 10-month-old female infant with purpura fulminans is reported. The patient had clotting abnormality compatible with consumption coagulopathy. Histopathological examination revealed the presence of microthrombi. Heparin was effective in correcting the clotting defects. The infant also suffered from microangiopathic haemolytic anaemia. She died 17 days after the onset of the illness from infection in spite of antibiotic therapy. ImagesFig. 1Fig. 2Fig. 3 PMID:4469044

  3. Idiopathic thromobocytopenic purpura in two mothers of children with DiGeorge sequence: A new component manifestation of deletion 22q11?

    SciTech Connect

    Levy, A.; Philip, N.; Michel, G.

    1997-04-14

    The phenotypic spectrum caused by the microdeletion of chromosome 22q11 region is known to be variable. Nearly all patients with DiGeorge sequence (DGS) and approximately 60% of patients with velocardiofacial syndrome exhibit the deletion. Recent papers have reported various congenital defects in patients with 22q11 deletions. Conversely, some patients have minimal clinical expression. Ten to 25% of parents of patients with DGS exhibit the deletion and are nearly asymptomatic. Two female patients carrying a 22q11 microdeletion and presenting with idiopathic thrombocytopenic purpura are reported. Both had children with typical manifestations of DGS. 12 refs., 4 figs., 1 tab.

  4. Purpura of the Face and Neck: An Atypical Clinical Presentation Revealing a Hepatosplenic T Cell Lymphoma

    PubMed Central

    Kuonen, François; Bucher, Maya; de Leval, Laurence; Vernez, Maxime; Gilliet, Michel; Conrad, Curdin; Feldmeyer, Laurence

    2014-01-01

    Background Hepatosplenic T cell lymphoma (HSTL) is a rare but very aggressive peripheral T cell lymphoma whose initial silent clinical presentation unfortunately delays the diagnosis and worsens the prognosis of patient survival. Efforts should be aimed at early recognition and treatment. Methods We describe a case of a 62-year-old woman who presented at our clinic with a non-palpable purpuric eruption of the face. Investigations revealed thrombocytopenia with hepatosplenomegaly, which showed rapid progression together with accentuation of the purpura. Two months later, a bone marrow biopsy revealed the diagnosis of a HSTL. Results The patient received six cycles of CHOP chemotherapy (vincristine, cyclophosphamide, doxorubicin, methylprednisolone) followed by a well-tolerated autologous bone marrow graft. Normalization of the platelet count resulted in regression of the purpuric rash. Conclusion To our knowledge, this is the first report of a facial thrombocytopenic purpura as the inaugural symptom of HSTL. It emphasizes the privileged position of the dermatologist for early recognition of potentially lethal HSTL. PMID:24707248

  5. Capnocytophaga canimorsus infection presenting with complete splenic infarction and thrombotic thrombocytopenic purpura: a case report

    PubMed Central

    2012-01-01

    Background Animal bites are typically harmless, but in rare cases infections introduced by such bites can be fatal. Capnocytophaga canimorsus, found in the normal oral flora of dogs, has the potential to cause conditions ranging from minor cellulitis to fatal sepsis. The tendency of C. canimorsus infections to present with varied symptoms, the organism’s fastidious nature, and difficulty of culturing make this a challenging diagnosis. Rarely, bacterial cytotoxins such as those produced by C. canimorsus may act as causative agents of TTP, further complicating the diagnosis. Early recognition is crucial for survival, and the variability of presentation must be appreciated. We present the first known case of C. canimorsus infection resulting in TTP that initially presented as splenic infarction. Case presentation 72-year-old Caucasian male presented with a four-day history of abdominal pain, nausea, vomiting, diarrhea, and intermittent confusion. On presentation, vital signs were stable and the patient was afebrile. Physical examination was unremarkable apart from petechiae on the inner left thigh, and extreme diffuse abdominal pain to palpation and percussion along with positive rebound tenderness. Initial investigations revealed leukocytosis with left shift and thrombocytopenia, but normal liver enzymes, cardiac enzymes, lipase, INR and PTT. Abdominal CT demonstrated a non-enhancing spleen and hemoperitoneum, suggesting complete splenic infarction. Although the patient remained afebrile, he continued deteriorating over the next two days with worsening thrombocytopenia. After becoming febrile, he developed microangiopathic hemolytic anemia and hemodynamic instability, and soon after was intubated due to hypoxic respiratory failure and decreased consciousness. Plasma exchange was initiated but subsequently stopped when positive blood cultures grew a gram-negative organism. The patient progressively improved following therapy with piperacillin-tazobactam, which was switched to imipenem, then meropenem when Capnocytophaga was identified. Conclusions There is a common misconception amongst practitioners that the presence of systemic infection excludes the possibility of TTP and vice versa. This case emphasizes that TTP may occur secondary to a systemic infection, thereby allowing the two processes to coexist. It is important to maintain a wide differential when considering the diagnosis of either TTP or C. canimorsus infection since delays in treatment may have fatal consequences. PMID:23267527

  6. How we use WinRho in patients with idiopathic thrombocytopenic purpura.

    PubMed

    Stotler, Brie A; Schwartz, Joseph

    2015-11-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disease that affects children and adults. WinRho SDF is a D immune globulin product that is Food and Drug Administration approved for the treatment of ITP in D+ pediatric and adult patients. WinRho is a plasma-derived biologic product dispensed from blood banks. Transfusion medicine physicians serve as a resource to health care providers regarding blood component and derivative usage and, as such, should be familiar with the use of WinRho for ITP, including the dosage, administration, and contraindications. This report details the transfusion medicine consultation practice and guidelines at a tertiary care academic medical center for the usage of WinRho SDF in patients with ITP. PMID:26094894

  7. Pruritis and palpable purpura from leeches in the Australian Rainforest

    PubMed Central

    Seiverling, Elizabeth V.; Khalsa, Amrit; Ahrns, Hadjh T.

    2014-01-01

    Leeches are prevalent in the Australian Rainforest. We report two cases of leech bites resulting in pruritis and palpable purpura. The dermatologic sequelae of leech bites, differential diagnosis of pruritic palpable purpura, leech bite treatment, prevention, and complications are reviewed.

  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. Psychogenic Purpura (Gardner-Diamond Syndrome).

    PubMed

    Jafferany, Mohammad; 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

  10. Postsplenectomy recurrence of idiopathic thrombocitopenic purpura: role of laparoscopic splenectomy in the treatment of accessory spleen

    PubMed Central

    LEO, C.A.; PRAVISANI, R.; BIDINOST, S.; BACCARANI, U.; BRESADOLA, V.; RISALITI, A.; TERROSU, G.

    2015-01-01

    Aim Idiopatic thrombocytopenic purpura (ITP) is the most common indication for splenectomy. The failure rate of surgery is about 8% and the failure rate after splenectomy is approximately 28% for all patients. When the presence of an accessory spleen is diagnosed, splenectomy is recommended. Laparoscopic approach is considered the first choice. Patients and methods At our Department, between July and November 2011 two patients underwent laparoscopic accessory splenectomy for recurrence of ITP. Both patients had a previously laparoscopic splenectomy. Preoperative Magnetic Resonance (MR) was performed in both the cases revealing the presence of an accessory spleen. Results The operative time was 105 and 100 minutes respectively. No perioperative complications occured. Hospital stay was four days in both cases. The first patient had a disease free period of two months; the second one of one month. Both patients restarted immunosuppressive therapy. Conclusions The relapse of thrombocytopenia post-splenectomy can be associated with the presence of an accessory spleen. The laparoscopic accessory splenectomy should be considered the first choice approach. Surgical accessory splenectomy allows a transitory remission of the disease. PMID:26712069

  11. Rituximab therapy for severe refractory chronic Henoch-Schönlein purpura.

    PubMed

    Donnithorne, Katherine J; Atkinson, T Prescott; Hinze, Claas H; Nogueira, Janaina B; Saeed, Shehzad A; Askenazi, David J; Beukelman, Timothy; Cron, Randy Q

    2009-07-01

    To report on the efficacy of rituximab (RTX) therapy in standard treatment-refractory, chronic Henoch-Schönlein purpura, a retrospective chart review of 3 pediatric patients treated with RTX for severe refractory chronic Henoch-Schönlein purpura was performed. All 3 patients responded to 1 or 2 courses of RTX without serious adverse events. PMID:19559299

  12. Vancomycin-induced Henoch-Schönlein purpura: a case report

    PubMed Central

    2012-01-01

    Introduction Henoch-Schönlein purpura is a small-vessel systemic vasculitis. Although its exact pathophysiology remains unknown, Henoch-Schönlein purpura has been reported in association with various medical conditions including hypersensitivity. We report the case of a patient with vancomycin-induced Henoch-Schönlein purpura. Case presentation A 42-year-old Caucasian man who had previously undergone a heart transplant was diagnosed as having an intra-abdominal abscess after he underwent a Hartmann procedure. At 15 days after initiation of antibiotic therapy including vancomycin, he developed a purpuric rash of the lower limbs, arthralgia, and macroscopic hematuria. At that time, our patient was already on hemodialysis for end-stage renal disease. Henoch-Schönlein purpura was diagnosed. After a second 15-day course of vancomycin, a second flare of Henoch-Schönlein purpura occurred. Skin biopsies showed leucocytoclastic vasculitis with IgA deposits and eosinophils in the peri-capillary inflammatory infiltrate, suggesting an allergic mechanism. After vancomycin was stopped, we did not observe any further flares. Only five cases of isolated cutaneous vasculitis, one case of lupus-like syndrome and one case of Henoch-Schönlein purpura after vancomycin treatment have been described to date in the literature. Conclusions Clinicians should be aware that systemic vasculitis can be induced by some treatments. Vancomycin is a widely prescribed antibiotic. Occurrence of rare but serious Henoch-Schönlein purpura associated with vancomycin requires its prompt discontinuation. PMID:22490390

  13. Acute infectious purpura fulminans due to probable spotted fever.

    PubMed

    Kundavaram, A; Francis, N R; Jude, A P J; Varghese, G N

    2014-01-01

    Purpura fulminans (PF) is associated with several infections, most notably with meningococcus, staphylococcus, and streptococcus infections. However, there are few reports of association of this entity with spotted fever from India. We report the case of a 55-year-old man who presented with fever, headache, and myalgia. On the seventh day of fever he developed nonblanching purple hemorrhagic purpura on the trunk and most prominently on the extremities consistent with purpura fulminans. Immunofluorescent assay confirmed the diagnosis of spotted fever. PF though common with rocky mountain spotted fever (RMSF) is rarely seen in association with Indian tick typhus, the usual cause of spotted fever in India. PMID:24823524

  14. Retiform purpura: a new stigmata of illicit drug use?

    PubMed

    Geller, Lauren; Whang, Talley B; Mercer, Stephen E; Phelps, Robert

    2011-01-01

    We report a 50-year-old woman who presented with a six-month history of recurrent retiform purpura of uncertain etiology. Laboratory findings included neutropenia, positive anticardiolipin IgM antibody, and a weakly positive p-ANCA. Histopathology revealed a leukocytoclastic vasculitis with intravascular thrombi. Urine toxicology screen was positive for cocaine. These findings are similar to recent reports of agranulocytosis and purpura induced by levamisole-tainted cocaine. A review of the clinical and histopathological findings associated with levamisole-induced purpura will be discussed. PMID:21382290

  15. Quantitative kinetics of In-111 autologous (In-AP) and homologous (Cr-HP) platelets in immune thrombocytopenic purpura (ITP)

    SciTech Connect

    Lotter, M.G.; Heyns, A.D.P.; Badenhorst, P.N.; Minnaar, P.C.

    1984-01-01

    Contrary to the accepted view, the authors have found that platelet turnover is not always increased in ITP if the mean platelet survival time (PS) is measured with In-AP. The authors investigated the possible cause of the discrepancy by comparing kinetics of In-AP with those of Cr-HP in 10 patients with ITP. PS was estimated with the multiple hit model. The equilibrium and final in vivo distribution of In-AP was quantitated with the geometrical mean method. The patients could be divided into either those with splenic or diffuse RES platelet destruction. The authors conclude that in ITP platelet survival of In-AP is significantly (P < .05) longer than that of Cr-HP. Platelet turnover measured with In-AP is only normal in patients with mainly splenic platelet sequestration. Results with Cr-HP give a false impression of PS. It seems that in ITP those patients with severe disease also have a platelet production defect.

  16. Purpura Fulminans Secondary to Rickettsial Infection: A Case Report

    PubMed Central

    Holyachi, Renuka; Kadeli, Deepak K

    2015-01-01

    Purpura fulminans is an acute life threatening disorder characterized by cutaneous haemorrhagic manifestations and necrosis caused by disseminated intravascular coagulation and dermal vascular thrombosis. In this case a 60-year-old male presented with purpuric lesions over both upper and lower limbs and consumption coagulopathy following rickettsial infection. It was diagnosed as purpura fulminans secondary to rickettsial infection with disseminated intravascular coagulation and treated with replacement of platelets and coagulation factors along with antibiotics and doxycycline. PMID:26673422

  17. Purpura Fulminans Secondary to Rickettsial Infection: A Case Report.

    PubMed

    Biradar, Siddanagouda; Holyachi, Renuka; Kadeli, Deepak K

    2015-11-01

    Purpura fulminans is an acute life threatening disorder characterized by cutaneous haemorrhagic manifestations and necrosis caused by disseminated intravascular coagulation and dermal vascular thrombosis. In this case a 60-year-old male presented with purpuric lesions over both upper and lower limbs and consumption coagulopathy following rickettsial infection. It was diagnosed as purpura fulminans secondary to rickettsial infection with disseminated intravascular coagulation and treated with replacement of platelets and coagulation factors along with antibiotics and doxycycline. PMID:26673422

  18. Solar capillaritis as a cause of solar purpura.

    PubMed

    Waters, A J; Sandhu, D R; Green, C M; Ferguson, J

    2009-12-01

    Appearance of purpura acutely after sun exposure is rare. We report a 51-year-old woman who repeatedly developed an asymptomatic petechial eruption on her legs after strong sun exposure. Investigation found an action spectrum within the ultraviolet A waveband, and histological examination of an evoked lesion found features of capillaritis. We briefly review the literature on solar purpura, and suggest that it is a feature of several distinct conditions, rather than a single condition. PMID:19793096

  19. Endoscopy in neutropenic and/or thrombocytopenic patients

    PubMed Central

    Tong, Michelle C; Tadros, Micheal; Vaziri, Haleh

    2015-01-01

    AIM: To evaluate the safety of endoscopic procedures in neutropenic and/or thrombocytopenic cancer patients. METHODS: We performed a literature search for English language studies in which patients with neutropenia and/or thrombocytopenia underwent endoscopy. Studies were included if endoscopic procedures were used as part of the evaluation of neutropenic and/or thrombocytopenic patients, yielding 13 studies. Two studies in which endoscopy was not a primary evaluation tool were excluded. Eleven relevant studies were identified by two independent reviewers on PubMed, Scopus, and Ovid databases. RESULTS: Most of the studies had high diagnostic yield with relatively low complication rates. Therapeutic endoscopic interventions were performed in more than half the studies, including high-risk procedures, such as sclerotherapy. Platelet transfusion was given if counts were less than 50000/mm3 in four studies and less than 10000/mm3 in one study. Other thrombocytopenic precautions included withholding of biopsy if platelet count was less than 30000/mm3 in one study and less than 20000/mm3 in another study. Two of the ten studies which examined thrombocytopenic patient populations reported bleeding complications related to endoscopy, none of which caused major morbidity or mortality. All febrile neutropenic patients received prophylactic broad-spectrum antibiotics in the studies reviewed. Regarding afebrile neutropenic patients, prophylactic antibiotics were given if absolute neutrophil count was less than 1000/mm3 in one study, if the patient was undergoing colonoscopy and had a high inflammatory condition without clear definition of significance in another study, and if the patient was in an aplastic phase in a third study. Endoscopy was also withheld in one study for severe pancytopenia. CONCLUSION: Endoscopy can be safely performed in patients with thrombocytopenia/neutropenia. Prophylactic platelet transfusion and/or antibiotic administration prior to endoscopy may be considered in some cases and should be individualized. PMID:26674926

  20. Sepsis-induced purpura fulminans caused by Pasteurella multocida

    PubMed Central

    Borges, Lisa; Oliveira, Nelson; Cássio, Isabel; Costa, Humberto

    2014-01-01

    A 52-year-old man was admitted with a cutaneous rash associated with septic shock and multiorganic failure, 6?days after a dog bite. He was started on empiric antibiotherapy and supportive measures. The patient's condition aggravated, with need for invasive mechanical ventilation and intermittent haemodialysis, and evolution from a petechiae-like rash to purpura and gangrene, culminating in bilateral lower limb amputation. The blood cultures revealed only Pasteurella multocida, after 10?days of incubation. P multocida infection is a rare cause of soft tissue infection that subsides with oral antibiotherapy. Infections causing sepsis are rare and appear in immunocompromised patients. Purpura fulminans induced by sepsis is a rare, life-threatening disorder. This syndrome should be recognised promptly, so early treatment is instituted. We found no case reports of purpura fulminans caused by Pasteurella infections in our literature review. PMID:24554680

  1. MMR vaccine and idiopathic thrombocytopaenic purpura

    PubMed Central

    Black, Corri; Kaye, James A; Jick, Hershel

    2003-01-01

    Aims To estimate the relationship between idiopathic thrombocytopaenic purpura (ITP) and the measles, mumps and rubella (MMR) vaccination in children; calculating the relative risk estimate for ITP with in 6 weeks after MMR vaccination and the attributable risk of ITP within 6 weeks after MMR vaccination. Methods Using the General Practice Research Database we identified children with a first-time diagnosis of ITP from a base population of children aged less than 6 years between January 1988 and December 1999. After describing the characteristics of all the children identified with ITP, we focused on cases aged 13–24 months to perform a population-based, case–control analysis to estimate the relative risk of developing ITP within 6 weeks after MMR vaccination. We also calculated the risk of ITP attributable to the MMR vaccination. Results Sixty-three children with a first time diagnosis of ITP were identified; 23 cases were between 13 and 24 months old. The relative risk estimate for ITP within 6 weeks after MMR vaccination, compared to the combined group of unvaccinated children and children vaccinated with MMR more than 26 weeks previously was 6.3 (95% CI 1.3–30.1). The attributable risk of developing ITP within 6 weeks after MMR vaccination was estimated to be 1 in 25 000 vaccinations (95% confidence interval 21 300, 89 400). Conclusion This study confirms the increased risk of ITP within 6 weeks after MMR vaccination. However, the attributable risk of ITP within 6 weeks after MMR vaccination is low. PMID:12534647

  2. Purpura Fulminans Due to Acquired Protein C Deficiency

    PubMed Central

    Mukherjee, Devdeep; Pal, Priyankar; Kundu, Ritabrata

    2015-01-01

    Purpura fulminans (PF) may be the presenting symptom in a patient with protein C (PC) deficiency. It is a hematological emergency and presents with extensive areas of hemorrhagic necrosis of the skin. PC deficiency is usually genetically inherited. However, we report a 1 year and 4 months boy, who presented with acquired PC deficiency possibly of postinfectious etiology and developed PF. PMID:26677306

  3. [Skin lesions and joint involvement in purpura fulminans (author's transl)].

    PubMed

    Allouis, M; Catier, P; Bracq, H; Babut, J M

    1980-10-01

    Until recently, purpura fulminans had a very prognosis. It can now be treated and the patient may survive but extensive skin necrosis may lead to septic arthritis. The authors have observed 4 cases of this disease. 3 had to suffer amputation of a lower limb. They describe the type of care recommended in order to limit the extent of the necrosis. PMID:6450996

  4. Purpura fulminans associated with acute West Nile virus encephalitis.

    PubMed

    Shah, Sheevam; Fite, Laura Paul; Lane, Natalie; Parekh, Palak

    2016-02-01

    Purpura fulminans is a progressive thrombotic disorder that presents with widespread purpura due to deficiency or dysfunction of protein C or protein S. Lesions present as well-demarcated erythematous macules that progress to irregular areas of hemorrhagic necrosis.West Nile virus is a member of the Flaviviridae family transmitted to humans through the bite of various mosquito species. It manifests as West Nile fever in 25% of those infected and less commonly as neuroinvasive disease. An African American man in his fortiespresented with altered mental status and was noted to have evidence of disseminated intravascular coagulation according to his lab data. He then developed dusky skin discoloration and systemic flaccid bullae with desquamation. Biopsy was consistent with purpura fulminans and the patient eventually developed symmetric peripheral gangrene, requiring amputations of all four extremities. Infectious work up revealed positive testing for IgM and IgG antibodies in serum and cerebrospinal fluid leading to the diagnosis of acute West Nile Virus encephalitis. We present this case to describe the rarely reported association of purpura fulminans with West Nile Virus infection. PMID:26686320

  5. Henoch-Schönlein Purpura in Northern Spain

    PubMed Central

    Calvo-Río, Vanesa; Loricera, Javier; Mata, Cristina; Martín, Luis; Ortiz-Sanjuán, Francisco; Alvarez, Lino; González-Vela, M. Carmen; González-Lamuño, Domingo; Rueda-Gotor, Javier; Fernández-Llaca, Héctor; González-López, Marcos A.; Armesto, Susana; Peiró, Enriqueta; Arias, Manuel; González-Gay, Miguel A.; Blanco, Ricardo

    2014-01-01

    Abstract The severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3–20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2–38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%). In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is favorable in most cases, depending largely on renal involvement. PMID:24646467

  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. Purpura and dermal thinning associated with high dose inhaled corticosteroids.

    PubMed Central

    Capewell, S; Reynolds, S; Shuttleworth, D; Edwards, C; Finlay, A Y

    1990-01-01

    OBJECTIVE--To assess the effect of high dose inhaled corticosteroids on skin. DESIGN--Cross sectional study of patients receiving treatment for chest diseases. SETTING--Outpatient chest clinic in a teaching hospital. PATIENTS--68 Patients divided into four groups of similar age--namely, 15 receiving long term oral prednisolone, 21 receiving high dose inhaled corticosteroids, 15 receiving low dose inhaled corticosteroids, and 17 controls. MAIN OUTCOME MEASURES--Skin thickness at three sites measured by A scan ultrasound and clinical assessment of purpura. RESULTS--Compared with controls patients in both the oral prednisolone treated group and the high dose inhaled corticosteroid treated group had significantly thinner skin at all three sites (group median thicknesses: prednisolone treated group 28-33% less than controls; high dose inhaled corticosteroid treated group 15-19% less than controls). Differences in skin thicknesses between the low dose inhaled corticosteroid treated group and the controls were trivial. The prevalence of purpura was significantly greater in patients receiving oral prednisolone (12/15 patients) and high dose inhaled corticosteroids (10/21) than in controls (2/17). CONCLUSION--Skin thinning and purpura represent further evidence of systemic effects of high dose inhaled corticosteroids. PMID:2372620

  8. Vascular purpura revealing a severe dilated cardiomyopathy with left ventricular apical thrombus.

    PubMed

    Seemann, Aurélien; De Prost, Nicolas; Paoletti, Marie-Thérèse; Sbidian, Emilie; Brun-Buisson, Christian; Valeyrie-Allanore, Laurence

    2012-10-01

    We present a case of vascular purpura revealing an intra-cardiac left-sided thrombus complicating an end-stage dilated cardiomyopathy. Vascular purpura main etiologies encompass the wide specturm of vasculitides and microvascular-occlusion syndromes. Among them, cardiac embolism represents an unusal but potentially severe etology. PMID:23233780

  9. Vascular purpura revealing a severe dilated cardiomyopathy with left ventricular apical thrombus

    PubMed Central

    Seemann, Aurélien; De Prost, Nicolas; Paoletti, Marie-Thérèse; Sbidian, Emilie; Brun-Buisson, Christian; Valeyrie-Allanore, Laurence

    2012-01-01

    We present a case of vascular purpura revealing an intra-cardiac left-sided thrombus complicating an end-stage dilated cardiomyopathy. Vascular purpura main etiologies encompass the wide specturm of vasculitides and microvascular-occlusion syndromes. Among them, cardiac embolism represents an unusal but potentially severe etology. PMID:23233780

  10. Retiform purpura in a patient with a history of cocaine use.

    PubMed

    Fthenakis, A; Klein, P A

    2011-01-01

    There have been rare published cases of retiform purpura related to cocaine use. Levamisole, a common adulterant, has been implicated as the etiologic agent. We describe a female patient, aged 48 years, with cocaine-related retiform purpura involving her face, abdomen, and legs and alert physicians to the dangers of levamisole-contaminated cocaine. PMID:21549087

  11. Romiplostim Injection

    MedlinePLUS

    ... of bleeding in people who have chronic idiopathic thrombocytopenic purpura (chronic ITP; an ongoing condition that may cause ... You may receive other medications for chronic idiopathic thrombocytopenic purpura along with romiplostim injection. Your doctor may decrease ...

  12. Special Blood Donation Procedures

    MedlinePLUS

    ... a type of abnormal antibody formation), and thrombotic thrombocytopenic purpura (a rare clotting disorder). In cytapheresis, excess numbers ... but generally does not cure them. However, thrombotic thrombocytopenic purpura can be cured with apheresis. Directed or designated ...

  13. Refractory Immunological Thrombocytopenia Purpura and Splenectomy in Pregnancy

    PubMed Central

    Bernal-Macías, Santiago; Fino-Velásquez, Laura-Marcela; Vargas-Barato, Felipe E.; Guerra-Galue, Lucio; Reyes-Beltrán, Benjamín; Rojas-Villarraga, Adriana

    2015-01-01

    Thrombocytopenia is defined as a platelet count of less than 100,000 platelets per microlitre (mcL). Thrombocytopenia develops in approximately 6-7% of women during pregnancy and at least 3% of these cases are caused by immunological platelet destruction. Herein, we present a pregnant woman who develops at the first trimester autoimmune thrombocytopenia purpura associated with positive antiphospholipid antibodies. The disease was refractory to pharmacological treatments but had a favourable response to splenectomy. The patient carried the pregnancy to term without complication and gave birth to a healthy baby girl. PMID:26798527

  14. Increased efficacy of breast cancer chemotherapy in thrombocytopenic mice

    PubMed Central

    Demers, Mélanie; Ho-Tin-Noé, Benoit; Schatzberg, Daphne; Yang, Janie J.; Wagner, Denisa D.

    2011-01-01

    Platelets contribute to homeostasis of the tumor vasculature by helping prevent hemorrhage. Thus, we hypothesized that inducing thrombocytopenia would increase tumor vascular leakiness and facilitate the effective delivery of chemotherapeutic agents to tumors. In a mammary carcinoma murine model, platelet depletion induced bleeding specifically at the tumor site, favoring the accumulation of fluorescently-labeled microspheres only in the tumor. Moreover, induction of thrombocytopenia in tumor-bearing mice before injection of paclitaxel increased its intratumoral accumulation and reduced growth of both slow- and fast-growing tumors, compared to mice with normal platelet counts that were treated only with paclitaxel. Histological analysis confirmed the expectation of an increase in tumor apoptosis and a reduction in tumor proliferation in thrombocytopenic mice receiving chemotherapy. No increased toxicity was seen in other organs or blood cells. Taken together, our results indicate that low platelet count selectively induces leakiness of tumor vessels and favors the delivery of chemotherapy to tumor sites, enhancing its tumoricidal effects. PMID:21212409

  15. Relationship between chronic tonsillitis and Henoch-Schonlein purpura

    PubMed Central

    Yan, Min; Wang, Zhan; Niu, Na; Zhao, Jianxia; Peng, Jian

    2015-01-01

    The aim of this study was to explore the relationship between children’s chronic tonsillitis and Henoch-Schonlein purpura (HSP). We randomly selected 56 cases of HSP children with chronic tonsillitis during December 2009 to December 2012, 26 cases for surgery group and 30 cases for non-surgery. The duration of abdominal pain and rash, 24 hours urine protein quantity, urine red blood cell count, titre of anti streptolysin O (ASO) and complement C3 (C3) were compared and analyzed with statistical method. Compared with the non-surgery group, the duration of abdominal pain and rash, overcast days of urine protein and occult blood in the surgery group were improved significantly (P < 0.05). 24 hours urine protein quantity and urine red blood cell count of the surgery group were improved significantly after surgery (P < 0.01). Chronic tonsillitis was one of the important factors leading to recurrent rash and inducing Henoch-Schonlein purpura nephritis. Tonsillectomy was an alternative mean to treat HSP children with chronic tonsillitis. PMID:26550368

  16. Urological Manifestations of Henoch-Schonlein Purpura: A Review

    PubMed Central

    Dalpiaz, Amanda; Schwamb, Richard; Miao, Yimei; Gonka, Jacquelyn; Walzter, Wayne; Khan, Sardar A.

    2015-01-01

    Henoch-Schonlein purpura (HSP) is an immune-mediated systemic vasculitis generally found in children. The standard manifestations of HSP are palpable purpura, arthritis, abdominal pain, and renal complications. Although less common, there are significant urological manifestations associated with HSP. The primary objective of this review is to encourage better understanding and management of HSP by emphasizing the common and rare manifestations of HSP, how they are diagnosed, and the latest treatment options for mild to severe complications. Medline searches of HSP and its urological manifestations were conducted along with searches on current diagnostic and treatment methods. Urological manifestations of HSP involve the kidney, ureter, bladder, prostate, scrotum, testicle, and penis. Diagnosis and management of HSP are not always clear due to differential diagnosis and diversity of symptom presentation. Treatment for HSP is mainly supportive and includes use of nonsteroidal anti-inflammatory drugs for pain relief. In more severe cases, glucocorticoids, methylprednisolone, plasmapheresis, and peritoneal and hemodialysis are reported successful. It is important to note different symptoms of HSP in order to distinguish HSP from other diseases. Early diagnosis may prevent severe complications. Treatment options vary from conservative to invasive depending on the severity of the disease and time frame of diagnosis.

  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. Multiple myeloma developing during long-term clinical course of refractory immune thrombocytopenic purpura: a case report and review of literature

    PubMed Central

    Yao, Han; Zhang, Xi; Liu, Jia; Zhu, Lidan; Chen, Guo; Wu, Sha; Gao, Lei

    2015-01-01

    Immune thrombocytopenia (ITP) is an acquired, immune-mediated disease that is characterized by increased destruction of platelets by autoantibodies. Although the onset of the disease and clinical course are highly variable, the disease typically has a benign course. ITP associated with multiple myeloma (MM) has been rarely reported; it is even rarer for MM to develop during a long-term ITP (almost 20 years). Here, we first report on a case with a 20-year long clinical course of refractory ITP followed by newly diagnosed MM. PMID:26823908

  19. Purpura fulminans associated with Streptococcus pneumoniae septicemia in an asplenic pediatric patient.

    PubMed

    Konda, S; Zell, D; Milikowski, C; Alonso-Llamazares, J

    2013-09-01

    Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans. PMID:23985086

  20. /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.

  1. Henoch-Schönlein Purpura Associated with Gangrenous Appendicitis: A Case Report

    PubMed Central

    SEMEENA, NK; ADLEKHA, Shashikant

    2014-01-01

    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

  2. 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

  3. A case study of thrombotic thrombocytopaenic purpura: a 'powerful poison'.

    PubMed

    Cox, Dani; Coyer, Fiona

    2004-05-01

    This paper presents the case of a previously well 72 year old man who spent 86 days in the intensive care unit (ICU) following a remarkable and explosive presentation of the rare condition thrombotic thrombocytopaenic purpura (TTP). TTP is an intravascular platelet aggregation disorder that, without treatment, is associated with significantly high mortality rates. This paper discusses TTP in terms of its presentation, pathophysiology, diagnosis and management. In addition to TTP, the patient developed a number of comorbidities during his stay in ICU. Particular attention is given to two major problems: acute renal failure and prolonged encephalopathy. These issues, along with the initial diagnosis of TTP, resulted in the patient remaining in ICU for a longer period than otherwise might have been expected. Despite many obstacles, the patient recovered and was discharged from hospital 116 days after initial presentation. PMID:15218818

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

    PubMed Central

    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

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

    PubMed

    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

    2015-05-21

    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

  6. Purpura fulminans secondary to rickettsial infections: A case series

    PubMed Central

    Katoch, Saloni; Kallappa, Ravindra; Shamanur, Murugesh B.; Gandhi, Sneha

    2016-01-01

    Purpura fulminans (PF) is a descriptive term used to describe a heterogeneous group of disorders characterized by rapidly progressive purpuric lesions that may develop into extensive areas of skin necrosis, and peripheral gangrene. This rare disorder is associated with laboratory evidence of consumptive coagulopathy and is often fatal. PF is usually associated with many infections, most notably with meningococcal, staphylococcal, and streptococcal infections. However, there are very few reports of this entity with spotted fever and scrub typhus from India. Rickettsial infections are an underdiagnosed group of diseases presenting as acute febrile illness, with high mortality in untreated cases. Of the available tests, Weil–Felix is a handy and economical tool for early diagnosis of this fatal disease especially in resource poor settings. We present four infants with PF secondary to rickettsial fever diagnosed by the Weil–Felix test.

  7. [A case of ureteritis in Henoch-Shönlein purpura].

    PubMed

    Moyano, M J; Alvarez, J; Millán, A; Amor, J

    2006-01-01

    Henoch-Schönlein purpura (HSP) is a multisystemic disorder mainly affecting the skin, joints, gastrointestinal tract, and kidneys but sometime rare complications that have been reported include urologic manifestations. We report a case of a 63 year old man was admitted to the hospital because a neurologic abnormalities, gastrointestinal blood loss and acute renal failure. One year before HSP was dignosed by percutaneous renal biopsy. A few days later admission the temperature was 38 masculineC and urine cultures yielded Echerichia Coli. An angio-magnetic resonance of the abdomen showed a marked dilatation of the distal left ureter with a level inside. Therapy with corticosteroids improved a clinical features and the usual renal function was recovered. PMID:17117908

  8. The role of platelets in mesangial localization: carbon uptake in thrombocytopenic rats.

    PubMed Central

    Chia, Y. C.; Cattell, V.

    1985-01-01

    The role of platelets in mesangial localization has been studied in Lewis rats following a single intravenous injection of colloidal carbon 32 mg/100 g body weight. Following carbon injection there was an abrupt thrombocytopenia (peripheral platelet count at 10 min 165 +/- 107 X 10(3)/mm3). Temporary sequestration of platelets in lung, liver and spleen was demonstrated using quinacrine-labelled platelets. Carbon was quantitated in blood, lung, liver and spleen by digestion and spectrophotometry and in glomerular mesangium by particle counting of histological sections under oil-immersion microscopy. In thrombocytopenic rats (busulphan 17.5 mg/kg weight) blood carbon levels (up to 1 h after injection) were higher than normal controls (P less than 0.01) and mesangial carbon content at 24 h was significantly increased (P less than 0.01). No significant alteration in mononuclear phagocytic function was detected at 24 h. In platelet-restored thrombocytopenic rats, (busulphan-treated, infused with homologous platelets) blood and mesangial carbon levels were decreased towards normal values. These findings show that (1) platelets are involved in the initial removal of carbon from the blood (2) mesangial localization is related to blood levels and (3) platelet numbers affect both these parameters. The finding of increased mesangial deposition in thrombocytopenic rats may have significance for immune complex glomerulonephritis where platelet numbers may be low due to persistent platelet activation. PMID:4027179

  9. Purpura Fulminans in Toxic Epidermal Necrolysis: Case Report and Review.

    PubMed

    Jones, Elizabeth; Stair-Buchmann, Megan; Kotliar, Sophia; Haith, Linwood

    2015-01-01

    Purpura fulminans (PF) and toxic epidermal necrolysis (TEN) are rare and life-threatening diseases. TEN is a notorious epidermolytic condition, most cases of which are drug induced. TEN is a more severe variant of epidermal necrolysis than Stevens-Johnson syndrome, as it affects a greater percentage of skin surface area. PF occurs in acute severe infections, deficiencies of protein C and S, and rarely, is idiopathic. PF is a thrombotic disorder of hemorrhagic cutaneous infarction and disseminated intravascular coagulation. While the two diseases are distinct in etiology, their clinical presentations can be strikingly similar. This report illustrates the clinical overlap between PF and TEN and reveals the potential for the diseases to coincide. The case of a patient with biopsy-proven TEN who developed PF was reviewed in detail. The topics of PF and TEN were searched using the MEDLINE database to investigate the relationship between the two diseases. Our case report raises diagnostic suspicion for PF in cases of TEN, particularly in patients with rapid clinical deterioration and failure of conventional management. In addition to the case presented from our institution, a similar case has been reported in which biopsy-proven PF clinically mimicked the epidermolytic condition Stevens-Johnson syndrome. These observations reflect that, although rare, conditions of epidermal necrolysis and PF may coincide more frequently than currently recognized. PMID:25412057

  10. Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura

    PubMed Central

    Bernstein, Gregory R.; Malik, Zubair; Schey, Ron

    2015-01-01

    A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis. PMID:26504868

  11. 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

  12. Parallel-ridge pattern on dermatoscopy: observation in a case of purpura traumatica pedis

    PubMed Central

    Feci, Luca; Fimiani, Michele; Rubegni, Pietro

    2015-01-01

    Dermatologists are often referred urgent cases of acral hematoma by general practitioners and sports medicine specialists for the purpose of excluding warts, nevi or melanoma. Acral hematoma is often a cause of anxiety to patients and their families. Here, we report a case of purpura traumatica pedis, referred to us as suspected plantar melanoma because of the finding of parallel-ridge pattern on dermatoscopic examination. To avoid unnecessary and costly procedures, doctors should inquire about any episode of physical exertion before the onset of purpura, recording the lesion’s anatomic site (e.g., unilateral vs. bilateral involvement) and clinical features. PMID:26693086

  13. 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

  14. Group A Escherichia coli-related purpura fulminans: an unusual manifestation due to an unusual strain?

    PubMed

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

    2014-12-01

    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

  15. A Novel Use of Tisseel in the Setting of Uncontrolled Bleeding in a Thrombocytopenic Patient With Idiopathic Thrombocytopenia

    PubMed Central

    Fisher, John S.; Gonzalez, Ricardo; Spiess, Philippe E.

    2015-01-01

    We present a case of an 87-year-old female who was evaluated for an 8.5 cm left sided renal mass concerning for malignancy. The patient was transiently thrombocytopenic over the previous 4 months with platelet counts ranging from 50,000 to 125,000 plt/mcL and experienced diffuse hemorrhage during radical nephrectomy with failure to achieve mechanical hemostasis or fulguration. Following Surgicel (Ethicon; Somerville, New Jersey) application, we applied Tisseel (Baxter; Deerfield, IL) to the nephrectomy bed with complete hemostasis of bleeding foci. Tisseel saved this thrombocytopenic patient with uncontrolled bleeding and should have this clinical utility recognized. PMID:26793579

  16. Replacement therapy with protein C concentrate in infants and adolescents with meningococcal sepsis and purpura fulminans.

    PubMed

    Ettingshausen, C E; Veldmann, A; Beeg, T; Schneider, W; Jäger, G; Kreuz, W

    1999-01-01

    We report the effects of substitution with a virus-inactivated protein C (PC) concentrate in disseminated intravascular coagulation (DIC) in infants and children with meningococcal sepsis associated with purpura fulminans. It was a prospective open-label study. Eight pediatric and adolescent patients age 0.2 to 18.25 years with DIC associated with severe acquired PC deficiency (range 0.02 to 0.48 IU/mL; median, 0.22 IU/mL) in meningococcal septic shock and purpura fulminans were studied. Replacement therapy was initiated with a virus-inactivated PC concentrate with an initial intravenous bolus of 80 to 120 IU/kg followed by 50 IU/kg up to six times per day as an adjunctive therapeutic regimen to otherwise optimal intensive care treatment. After initial PC administration, plasma PC levels rose to normal ranges and were maintained under PC replacement therapy. Improving or even normalizing global hemostatic parameters were assessed in all patients. Markedly elevated plasminogen activator inhibitor type 1 (PAI-1) levels prior to treatment, reflecting a reduced fibrinolytic potential, decreased rapidly under PC substitution. Concomitantly improving signs of purpura fulminans reflected by decreasing size of skin lesions, demonstrated a restoring microcirculation. Six of the eight patients survived. One patient required limb amputation; two patients died because of multiorgan failure. Both presented with a severely low plasma PC activity of 0.02 IU/mL on admission to the hospital. No adverse effects were observed with the PC concentrate administration. It can be concluded that the administration of PC concentrate had a marked benefit on the deranged coagulation status of patients with purpura fulminans and meningococcal septicemia. Normalization or even partial correction of hemostasis as well as improvement of microcirculation accompanied by improving signs of purpura fulminans were demonstrated in all patients. PMID:10632475

  17. Thromboelastometric Monitoring of the Hemostatic Effect of Platelet Concentrates Transfusion in Thrombocytopenic Children Undergoing Chemotherapy.

    PubMed

    Ziegler, Bernhard; Solomon, Cristina; Cadamuro, Janne; Jones, Neil

    2015-09-01

    Prophylactic platelet concentrates transfusion represents a therapeutic choice in patients with chemotherapy-induced thrombocytopenia. This prospective, non-interventional study evaluated the effects of platelet concentrates transfusion on thromboelastometric parameters of platelet function in 36 transfusion occasions for 11 thrombocytopenic children undergoing chemotherapy. Pre- and posttransfusion (1-2 hours) blood samples were analyzed using standard coagulation tests and thromboelastometry (ROTEM) measurements (EXTEM and FIBTEM tests). Platelet component of the clot was calculated based on the EXTEM and FIBTEM maximum clot elasticity (MCE) results. After transfusion, mean platelet count increased from 16.5 × 10(9)/L to 43.0 × 10(9)/L (P < .001) and platelet component increased from 34.1 to 73.0 (P < .001). Statistically significant increases for posttransfusion EXTEM parameters A10, A20, and maximum clot firmness (MCF) were observed compared to pretransfusion values (P < .001). The EXTEM ?-angle values increased posttransfusion (P < .05). The FIBTEM measurements were comparable pre- and posttransfusion. The study showed that platelet concentrates transfusion in thrombocytopenic children undergoing chemotherapy improves platelet-related coagulation pattern. PMID:25525046

  18. Thromboelastometric Monitoring of the Hemostatic Effect of Platelet Concentrates Transfusion in Thrombocytopenic Children Undergoing Chemotherapy

    PubMed Central

    Solomon, Cristina; Cadamuro, Janne; Jones, Neil

    2015-01-01

    Prophylactic platelet concentrates transfusion represents a therapeutic choice in patients with chemotherapy-induced thrombocytopenia. This prospective, non-interventional study evaluated the effects of platelet concentrates transfusion on thromboelastometric parameters of platelet function in 36 transfusion occasions for 11 thrombocytopenic children undergoing chemotherapy. Pre- and posttransfusion (1-2 hours) blood samples were analyzed using standard coagulation tests and thromboelastometry (ROTEM) measurements (EXTEM and FIBTEM tests). Platelet component of the clot was calculated based on the EXTEM and FIBTEM maximum clot elasticity (MCE) results. After transfusion, mean platelet count increased from 16.5 × 109/L to 43.0 × 109/L (P < .001) and platelet component increased from 34.1 to 73.0 (P < .001). Statistically significant increases for posttransfusion EXTEM parameters A10, A20, and maximum clot firmness (MCF) were observed compared to pretransfusion values (P < .001). The EXTEM α-angle values increased posttransfusion (P < .05). The FIBTEM measurements were comparable pre- and posttransfusion. The study showed that platelet concentrates transfusion in thrombocytopenic children undergoing chemotherapy improves platelet-related coagulation pattern. PMID:25525046

  19. Expansion of Circulating T Follicular Helper Cells in Children with Acute Henoch-Schönlein Purpura

    PubMed Central

    Xie, Jue; Liu, Yan; Wang, Lei; Ruan, Guoxiang; Yuan, Huiming; Fang, Hong; Wu, Jianyong; Cui, Dawei

    2015-01-01

    Henoch-Schönlein purpura (HSP) is a common systemic small vessel vasculitis in children with disorder autoimmune responses. T follicular helper (TFH) cells play crucial roles in regulating immune responses. The aim of our study was to investigate the probable role of TFH cells in the pathogenesis of children with HSP. In this study, the frequency of circulating CXCR5+CD4+TFH cells with inducible costimulator (ICOS) expression in the children with acute HSP was significantly higher than that in healthy controls (HCs) but not CXCR5+CD4+TFH cells with programmed death-1 (PD-1) expression. Moreover, serum levels of IL-21 and IL-6 cytokines, IgA, and C3 in HSP children were also significantly higher than those in HCs. A positive correlation was observed between the frequencies of circulating ICOS+CXCR5+CD4+TFH cells and the serum IL-21 or IgA levels of acute HSP children, respectively. Additionally, the mRNA expression levels of interleukin- (IL-) 21, IL-6, and transcriptional factors (B-cell lymphoma-6, Bcl-6) were also significantly increased in peripheral blood from acute HSP children compared to HCs. Taken together, these findings suggest that TFH cells and associated molecules might play critical roles in the pathogenesis of HSP, which are possible therapeutic targets in HSP children. PMID:26491701

  20. Terminal Ileitis as a Feature of Henoch-Schönlein Purpura Masquerading as Crohn Disease in Adults.

    PubMed

    Sampat, Hemal N; McAllister, Brian P; Gaines, Darryl D; Ostrov, Barbara

    2016-03-01

    Henoch-Schönlein purpura (HSP), more recently termed immunoglobulin A (IgA) vasculitis, is a systemic small-vessel vasculitis characterized by perivascular IgA deposition. This disease manifests clinically as palpable purpura, arthralgia, gastrointestinal symptoms, and renal dysfunction. Although ileitis can be seen in HSP, terminal ileitis is virtually pathognomonic for Crohn disease. We present a comprehensive review of the literature on this association, including 2 cases of our own, to demonstrate the importance of considering HSP in the differential diagnosis of ileitis suggestive of Crohn disease. We review the growing body of literature suggesting a pathophysiologic link between the conditions, possibly through an IgA-mediated mechanism. PMID:26906301

  1. [Meningococcal purpura fulminans: treatment with recombinant protein C activator in 3 cases].

    PubMed

    Salinas, U; Unzueta, J; Vidarte, M A; Rodrigo, M P; Gómez, J J; Aguilera, L

    2007-10-01

    Purpura fulminans is a serious disease associated with high rates of morbidity and mortality. It usually leads to disseminated intravascular coagulation and septic shock related to reduced levels of protein C. Recombinant protein C (rPC) activator has been used successfully to inhibit this process. Intracranial hemorrhages are the most important, life-threatening adverse effects of treatment with rPC activator. We report 3 cases of patients with meningococcal purpura fulminans who developed septic shock and multiorgan dysfunction. They were treated with the protocol for septic shock, antibiotics and rPC activator from the time of admission, and improvement in hemodynamic dysfunction was observed within hours in all patients. All received platelet replacement transfusions. Subarachnoid bleeding complications occurred in 2 patients. One patient died 5 days after admission and 2 were discharged from the intensive recovery care unit 28 days after admission. PMID:17993100

  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. Petechiae and purpura: the ominous and the not-so-obvious?

    PubMed

    Block, Stan L

    2014-08-01

    Petechiae and purpura are among the most alarming findings a pediatrician will commonly observe in the office. Severity of illness can range from a temper tantrum, to common viral infections, to the most deadly infections and diseases. To avoid many of the pitfalls in diagnosis, practitioners will need to be thorough in history taking, assessing fever and immunization status, and physical examination. In addition, a few simple laboratory tests will usually be needed and possibly a manual differential. PMID:25102482

  4. Mycoplasma pneumoniae as a trigger for Henoch-Schönlein purpura in children.

    PubMed

    Ku?ma-Mroczkowska, El?bieta; Pa?czyk-Tomaszewska, Ma?gorzata; Szmigielska, Agnieszka; Szymanik-Grzelak, Hanna; Roszkowska-Blaim, Maria

    2016-01-01

    Mycoplasma pneumoniae is one of the most common causes of respiratory tract infections in children. Extrapulmonary manifestations are seen in up to 25% of infected patients. Extrapulmonary complications are associated with the central nervous system, gastrointestinal tract, skin changes, myocarditis, pericarditis, hemolytic anemia, thrombocytopenia and thrombosis. The majority of extrapulmonary symptoms are associated with skin changes such as exanthematous skin eruptions, erythema nodosum, urticaria, Stevens-Jonson syndrome. M. pneumoniae stimulates production of the interleukins and tumor necrosis factor (TNF) ? and can cause vasculitis. Henoch-Schönlein purpura (HSP) is a leucoclastic vasculitis that affects small vessels. Clinical manifestations of HSP include typical rash, arthritis, gastrointestinal and sometimes renal involvement. The main feature in HSP is abnormal IgA deposits in vessel walls. Circulating abnormal glycosylated IgA 1 and IgG antibodies form immune complexes: IgA1-IgG and anti-IgA 1. Immune complexes activate cytokines, parts of complement and influence directly the endothelium. We report cases of three children with Henoch-Schönlein purpura with prolonged and recurrent skin and joint changes. The serological analysis (positive serum IgM) confirmed Mycoplasma pneumoniae infection. Treatment with clarithromycin caused complete regression of disease. We suggest that in the case of prolonged symptoms of vasculitis due to Henoch-Schönlein purpura, Mycoplasma pneumonia infection may be a potential cause of exacerbation of the disease. PMID:26862316

  5. Mycoplasma pneumoniae as a trigger for Henoch-Schönlein purpura in children

    PubMed Central

    Pańczyk-Tomaszewska, Małgorzata; Szmigielska, Agnieszka; Szymanik-Grzelak, Hanna; Roszkowska-Blaim, Maria

    2016-01-01

    Mycoplasma pneumoniae is one of the most common causes of respiratory tract infections in children. Extrapulmonary manifestations are seen in up to 25% of infected patients. Extrapulmonary complications are associated with the central nervous system, gastrointestinal tract, skin changes, myocarditis, pericarditis, hemolytic anemia, thrombocytopenia and thrombosis. The majority of extrapulmonary symptoms are associated with skin changes such as exanthematous skin eruptions, erythema nodosum, urticaria, Stevens-Jonson syndrome. M. pneumoniae stimulates production of the interleukins and tumor necrosis factor (TNF) α and can cause vasculitis. Henoch-Schönlein purpura (HSP) is a leucoclastic vasculitis that affects small vessels. Clinical manifestations of HSP include typical rash, arthritis, gastrointestinal and sometimes renal involvement. The main feature in HSP is abnormal IgA deposits in vessel walls. Circulating abnormal glycosylated IgA 1 and IgG antibodies form immune complexes: IgA1-IgG and anti-IgA 1. Immune complexes activate cytokines, parts of complement and influence directly the endothelium. We report cases of three children with Henoch-Schönlein purpura with prolonged and recurrent skin and joint changes. The serological analysis (positive serum IgM) confirmed Mycoplasma pneumoniae infection. Treatment with clarithromycin caused complete regression of disease. We suggest that in the case of prolonged symptoms of vasculitis due to Henoch-Schönlein purpura, Mycoplasma pneumonia infection may be a potential cause of exacerbation of the disease. PMID:26862316

  6. Association of endothelial nitric oxide synthase gene polymorphism with the risk of Henoch-Schönlein purpura/Henoch-Schönlein purpura nephritis.

    PubMed

    Zhong, Weiqiang; Zhou, Tian-Biao; Jiang, Zongpei

    2015-04-01

    Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future. PMID:25585947

  7. Hemoglobinuria test

    MedlinePLUS

    ... Hemolytic uremic syndrome (HUS) Kidney infection Kidney tumor Malaria Paroxysmal nocturnal hemoglobinuria Paroxysmal cold hemoglobinuria Sickle cell anemia Thalassemia Thrombotic thrombocytopenic purpura (TTP) Transfusion reaction Tuberculosis

  8. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2015-10-20

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  9. IgA-containing circulating immune complexes in dermatitis herpetiformis, Henoch-Schönlein purpura, systemic lupus erythematosus and other diseases.

    PubMed Central

    Hall, R P; Lawley, T J; Heck, J A; Katz, S I

    1980-01-01

    The sera of patients with dermatitis herpetiformis, Henoch-Schönlein purpura and systemic lupus erythematosus were examined for IgA-containing immune complexes using a newly described radioimmunoassay. The IgG Raji cell radioimmunoassay and the 125I-C1q binding assay were also used to detect IgG- and IgM- containing soluble immune complexes. IgA-containing immune complexes were found in the sera of twelve of forty-nine (24%) patients with dermatitis herpetiformis, four of six (67%) patients with Henoch-Schönlein purpura, and seven of ten (70%) patients with systemic lupus erythematosus. IgG- or IgM- containing immune complexes were also found in six of forty-seven patients with dermatitis herpetiformis, in one of six patients with Henoch-Schönlein purpura, and in nine of ten patients with systemic lupus erythematosus, by either the 125I-Clq binding assay or the IgG Raji cell assay. The finding of soluble IgA immune complexes in a high percentage of patients with systemic lupus erythematosus and Henoch-Schönlein purpura suggests that they may play an important role in the pathogenesis of these diseases. In contrast, their low prevalence in patients with dermatitis herpetiformis suggests that IgA-containing immune complexes may not play a major role in the pathogenesis of dermatitis herpetiformis. PMID:7418261

  10. Schönlein-henoch purpura in children and adults: diagnosis, pathophysiology and management.

    PubMed

    Rostoker, G

    2001-01-01

    Schönlein-Henoch syndrome is a form of systemic small-vessel vasculitis, characterised by vascular and/or mesangial immunoglobulin A1 deposits. The main clinical manifestations are vascular purpura, predominating on the lower limbs, and articular, gastrointestinal and renal symptoms. Pulmonary, cardiac, genital and neurological symptoms have also be observed. The syndrome usually affects children, whereas it is rare in adults. The frequency of renal involvement varies between individual studies (from 20 to 100%). Renal manifestations are usually mild and transient, although chronic nephropathies may occur. Overall, an estimated 2% of children with Schönlein-Henoch purpura progress to renal failure and up to 20% of children with nephritis treated in specialised centres require haemodialysis. The renal prognosis appears to be worse in adults. Aetiological investigations are required, as a triggering factor is found in approximately half the patients (e.g. viral, bacterial and parasitic infections, drugs, toxins, systemic diseases and cancer). Dapsone has beneficial effects on cutaneous, gastrointestinal and articular manifestations in adults, especially those with chronic forms. Corticosteroids may be useful for refractory abdominal pain. Methylprednisolone pulse therapy, immunosuppressive drugs (e.g. cyclophosphamide and azathioprine), plasma exchange and polyclonal immunoglobulin therapy are beneficial in very rare life-threatening forms of the disease and in rare instances where renal function is compromised. PMID:11437679

  11. [Varicella-associated purpura fulminans and deep vein thrombosis: a pediatric case report].

    PubMed

    Baur, A; Pouyau, R; Meunier, S; Nougier, C; Teyssedre, S; Javouhey, E; Floret, D; Gillet, Y

    2011-07-01

    Purpura fulminans (PF) and deep vein thrombosis are rare complications secondary to chicken pox disease. The presence of antibodies reflects an ongoing immunological process and requires specialized management. The present study reports a 4-year-old boy with no medical history who presented with purpura on the legs 10 days after chicken pox eruption. Laboratory tests showed a disseminated intravascular coagulation associated with low plasma protein C and S activities, and the presence of anti-protein S antibodies. A replacement therapy with protein C infusions and fresh frozen plasma was prescribed. The patient also underwent regular sessions of hyperbaric oxygen followed by the surgery. Fourteen days after the beginning of the purpuric lesions, he presented deep vein thrombosis (DVT) of the lower limbs and was treated with unfractionated heparin. This case report illustrates the pathophysiology of DVT occurring in a patient with chicken pox disease (i.e., acquired protein C and S deficiencies and anti-protein S autoantibodies) and emphasizes the utility of thrombophilia testing in order to better adapt treatment. PMID:21616651

  12. [Neonatal purpura fulminans without sepsis due to a severe congenital protein C deficiency].

    PubMed

    Hmami, F; Cherrabi, H; Oulmaati, A; Bouabdallah, Y; Bouharrou, A

    2015-10-01

    Severe congenital protein C deficiency is a rare life-threatening coagulopathy. In the early hours of life, the neonate presents with extensive purpura fulminans and substantial skin necrosis contrasting with a preserved general state and a negative infectious exam. Disseminated intravascular coagulation sets in secondarily. Prenatal outset of thrombotic events is a rare situation that worsens the prognosis, especially protein C replacement in utero is not available. We report a case of a male newborn of consanguineous parents who were asymptomatic carriers of heterozygous protein C deficiency. This infant presented prenatal ventricular hemorrhage with hydrocephalus and rapidly extensive postnatal skin necrosis that was not regressive in spite of fresh frozen plasma administrated after 24h of life. Prenatal diagnosis, early recognition, and urgent therapy with protein C replacement and anticoagulant treatment are crucial to improve the prognosis, avoid further damage after delivery, and prevent the devastating consequences of severe protein C deficiency. PMID:26228809

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

    PubMed

    Tutanç, Murat; Silfeler, Ibrahim; Ozgür, Tümay; Motor, Vicdan Köksaldı; Kurtoğlu, 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

  14. Association of acquired thrombotic thrombocytopaenic purpura in a patient with pernicious anaemia.

    PubMed

    Podder, Sidhertha; Cervates, Jose; Dey, Bimalangshu R

    2015-01-01

    Pernicious anaemia is an autoimmune disease caused by intrinsic factor antibody; it leads to vitamin B12 deficiency and is marked by ineffective erythropoiesis. Haematological features reveal macrocytosis, hyperchromasia and hypersegmented neutrophils. Schistocytes are typically seen in microangiopathy, such as in thrombotic thrombocytopaenic purpura (TTP)/haemolytic uraemic syndrome or disseminated intravascular haemolysis (DIC). We report a case of a patient with severe anaemia who presented to the emergency room. Peripheral smear revealed macrocytosis, hypersegmented neutrophils and marked schistocytosis. The patient also had high reticulocyte count with high serum lactate dehydrogenase, elevated D-dimer, low fibrinogen and low haptoglobin. Vitamin B12 level came back low and the presence of intrinsic factor antibody confirmed pernicious anaemia. ADAMTS13 level was noted to be mildly reduced, which raised the suspicion of the association of acquired TTP with pernicious anaemia. Acquired TTP is another autoimmune disorder and its association with pernicious anaemia needs further evaluation. PMID:26464409

  15. Pneumococcal Sepsis Complicated by Splenic Abscesses and Purpura Fulminans in a 15-Month-Old Child

    PubMed Central

    Pangonis, Scott; Patamasucon, Pisespong; Fitzpatrick, Ellen

    2016-01-01

    Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF) are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD) with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date. PMID:27006958

  16. Strongyloides stercoralis hyperinfection in patient with autoimmune hepatitis and purpura fulminans

    PubMed Central

    Rathor, Neha; Khillan, Vikas; Sarin, S. K.

    2016-01-01

    Strongyloidiosis is usually an asymptomatic chronic nematodal disease. The term hyperinfection is used to denote autoinfection, a phenomenon in which the number of worms increases enormously. Development or exacerbation of gastrointestinal and pulmonary symptoms is seen, (A) and the detection of increased numbers of larvae in stool and or sputum is the hallmark. It is known to occur with a change in immune status of the host; this can occur due to immunosuppressants. Cytomegalovirus (CMV) is also known to suppress host immunity. Due to the nonspecific presentation, the diagnosis is frequently missed, and the outcome remains poor with 15–87% mortality despite therapy. We report here a case of Strongyloides stercoralis hyperinfection following immunosuppressive therapy for autoimmune hepatitis and concomitant CMV infection with purpura fulminance and frank sepsis, with fatal outcome. PMID:26955218

  17. Immune thrombocytopaenic purpura: an autoimmune cross-link between infections and vaccines.

    PubMed

    Rinaldi, M; Perricone, C; Ortega-Hernandez, O-D; Perricone, R; Shoenfeld, Y

    2014-05-01

    Immune thrombocytopaenic purpura (ITP) is an autoimmune systemic disease detectable by the presence of low blood platelets count (<10(5)/µl) and the production of autoantibodies against glycoproteins expressed on the platelet surface. The clinical course is often acute, and life-threatening events may occur especially in children, with 52% of paediatric patients recovering either spontaneously or after treatment. A chronic ITP evolution is observed in 64% of adults, of whom 12% will develop an overlapping autoimmune disease. Several microbial agents such as CagA-positive Helicobacter pylori or Candida albicans and a number of viruses including CMV, EBV or HIV can potentially trigger ITP through molecular mimicry. Moreover, ITP improves after treatment of the underlying infection. Similarly, vaccines such as MMR may prompt ITP (IRR 5.48, 1.61-18.64, p < 0.006). Early recognition of the underlying microbial trigger and the removal of modifiable aetiopathogenetic factors should be integrated as a complementary treatment strategy in all patients who do not readily improve with standard ITP care. PMID:24763539

  18. Skin Necrosis and Purpura Fulminans in Children With and Without Thrombophilia-A Tertiary Center's Experience.

    PubMed

    Fruchtman, Yariv; Strauss, Tzipora; Rubinstein, Marina; Ben Harush, Miriam; Revel-Vilk, Shoshana; Kapelushmik, Joseph; Paret, Gideon; Kenet, Gili

    2015-10-01

    Purpura fulminans (PF) is a very rare clinicopathologic skin disorder comprising dermal microvascular thrombosis associated with perivascular hemorrhage of multiple origins. It may occur as the presenting symptom of severe congenital deficiency of protein C (PC) or protein S (PS) during the newborn period, or later in life following oral anticoagulant therapy with vitamin K antagonists, or of sepsis that may be associated with disseminated intravascular coagulation. Treatment consists of anticoagulants and PC concentrates during acute episodes. We report our experience in the diagnosis and management of pediatric PF. The medical records of the 6 children aged 2-16 years (median: 5 years) who presented with PF to our tertiary care center between 1996 and 2013 were studied. The thrombophilia workup revealed either the presence of congenital homozygous PC deficiency, prothrombotic polymorphisms (factor V Leiden and FIIG20210A heterozygosity), acquired PC/PS deficiency, or no discernible thrombophilia. The skin necrosis resolved following conservative fresh-frozen plasma/anticoagulant therapy in 2 cases, whereas 3 children required interventional plastic surgery. The sixth case, a 10-year-old child with severe PC deficiency, heterozygous factor V Leiden, and FIIG20210A, received recombinant activated PC. PF in childhood is rare and has multiple etiologies. Understanding of the variable pathogenesis and risk factors will facilitate diagnosis and appropriate clinical management. PMID:26436558

  19. IgA vasculitis (formerly Henoch-Schönlein purpura) in an adult with systemic lupus erythematosus.

    PubMed

    Bernardino, Vera; Mendes-Bastos, Pedro; Rodrigues, Ana; Riso, Nuno

    2015-01-01

    We report a case of a 65-year-old man with systemic lupus erythematosus (SLE) and antiphospholipid syndrome, presenting palpable purpuric lesions, necrotic blisters and swelling ankles, after a previous tracheobronchitis episode. Laboratory data were remarkable for mild proteinuria and imaging studies were normal. A skin biopsy showed IgA deposits on superficial dermal capillaries and IgA vasculitis (IgAV) (former Henoch-Schönlein purpura) was assumed. The patient was treated with colchicine, deflazacort and azathioprine, but as a regression in the purpuric lesions was noted, a decline in renal function was detected. A kidney biopsy revealed mesangial proliferation with IgA deposition and IgAV nephritis was considered. Immunosuppressive treatment was adjusted, with progressive normalisation of renal function and disappearance of proteinuria over a monthly follow-up; after 6?months, total remission was achieved. To the best of our knowledge, this is the first reported case of IgAV in an adult patient with SLE. PMID:26354836

  20. Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children

    PubMed Central

    Xiong, Li-Jing; Mao, Meng

    2016-01-01

    Helicobacter pylori (H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extra-intestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura (HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum IgA, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP. PMID:26862506

  1. Evaluation of Oxidative Stress and Erythrocyte Properties in Children with Henoch-Shoenlein Purpura

    PubMed Central

    Gurses, Dolunay; Parlaz, Nusret; Bor-Kucukatay, Melek; Kucukatay, Vural; Erken, Gulten

    2014-01-01

    Abstract Objective Pathogenesis of Henoch-Schönlein purpura (HSP) is not clearly defined. The present study was conducted to investigate the alterations in erythrocyte deformability and oxidative stress in HSP and to examine the possible relationship between erythrocyte deformability and organ involvement in this disease. Methods Plasma malondialdehyde (MDA) levels, total antioxidant status (TAS), erythrocyte deformability and aggregation were measured in 21 children with HSP at the disease onset and during the remission period in comparison with healthy subjects. Findings HSP patients at the active stage had significantly higher MDA and lower TAS levels (P<0.05). Erythrocyte deformability was decreased at the active-stage and increased again at the remission period of HSP (P<0.05). Erythrocyte deformability was significantly decreased at four different shear stresses in patients with gastrointestinal system or renal involvement; and decreased at six different shear stresses in patients with gastrointestinal system, and renal involvement compared to the patients without organ involvement (P<0.05). No significant difference was observed in aggregation parameters (P>0.05). Conclusion The present findings emphasize the association between impaired erythrocyte deformability and organ involvement in HSP. PMID:25535535

  2. 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.

  3. Association of ?-fibrinogen gene polymorphism and plasma fibrinogen and allergic purpura nephritis

    PubMed Central

    Gong, Jianhua; Xu, Qian; Hu, Fengqi; Yuan, Hai

    2015-01-01

    Objective: To investigate the association of ?-fibrinogen gene polymorphism with plasma fibrinogen and allergic purpura nephritis. Methods: We designed a case-control study (334 case and 300 control) to genotype the ?-fibrinogen gene -455G/A polymorphism. The genotype and allele frequencies between the case and control group were compared. And we also compared the Fg concentration between different genotype. Results: In the case group, there were 143 cases of GA type, accounting for 42.8%; there were 168 cases of GG type, accounting for 50.3%; there were 23 cases of AA type, accounting for 6.9%. While in the control group, GG type was the most common. There were 228 cases of GG type, accounting for 76%; there were 66 cases of GA type, accounting for 22%; there was 6 case of AA type, accounting for 2%. The frequency of Fg?-455G/A genotype between the two groups showed statistical significance (P<0.05). The levels of plasma Fg in the two groups showed statistical significance (P<0.01). In HSPN group Fg? GA and AA-type the concentration of Fg [(4.2 ± 0.5) g/L], compared with the GG genotype [(3.1 ± 0.4) g/L], was significantly increased with statistical significance (P<0.01). Conclusion: The Fg?-455G/A polymorphism was associated with the risk for HSPN and Fg concentration. PMID:26379943

  4. Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children.

    PubMed

    Xiong, Li-Jing; Mao, Meng

    2016-02-01

    Helicobacter pylori (H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extra-intestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura (HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum IgA, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP. PMID:26862506

  5. Acral purpura as leading clinical manifestation of dermatitis herpetiformis: report of two adult cases with a review of the literature.

    PubMed

    Tu, Honggang; Parmentier, Laurent; Stieger, Marco; Spanou, Zoe; Horn, Michael; Beltraminelli, Helmut; Borradori, Luca

    2013-01-01

    Dermatitis herpetiformis (DH) is an autoimmune disease that clinically manifests as pruritic vesicles and papules. The diagnosis of DH is often challenging because of its wide spectrum of clinical presentations. We here report 2 patients with DH in whom finger petechiae represented the initial and leading manifestation of the disease, and the confirmed diagnosis critically relied on immunopathological studies. Therefore, besides the classic causes, clinicians should also consider DH in the differential diagnosis of acral purpura, even in patients only presenting with discrete acral petechial lesions. We also review the recent literature regarding the rare cases of petechiae in adult DH patients. PMID:23970137

  6. Acute penile pain and swelling in a 4-year-old child with Henoch-Schönlein purpura.

    PubMed

    Tewary, Kishor Kumar; Khodaghalian, Bernadette; Narchi, Hassib

    2015-01-01

    Henoch-Schönlein purpura (HSP) is the most common vasculitis found in children. It usually affects the small vessels of the skin, joints, gastrointestinal tract and, more rarely, kidneys, brain, lungs and genitalia. Apart from classical presentation with purpuric rashes around buttocks and lower extremities, features such as arthralgia, abdominal pain, haematuria and proteinuria as well as scrotal swelling have been described in the literature. Penile involvement is rare and is not commonly described. We describe a child with HSP who developed penile involvement. We review the literature of all the cases reported in detail, in order to highlight useful clinical presentation, management and prognosis of this rare manifestation. PMID:25858918

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

    PubMed Central

    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

  8. HLA-B35, a common genetic trait, in a familial case of Henoch-Schoenlein purpura and Berger's disease.

    PubMed

    Pellegrin, M C; Matarazzo, L; Neri, E; Pennesi, M; Crovella, S

    2014-01-01

    Nephritis characterized by IgA mesangial depositions has been described both in Henoch-Schoenlein purpura (HSP) and in Berger's disease (BD), but common genetic traits are still uncertain. We report here the case of two brothers, the first affected by HSP with persistent nephritis and the second by BD, accidentally discovered as silent microhematuria 1 year after HSP onset in the first brother. HLA genotyping demonstrated the presence of HLA-B35 in both patients. Our findings reinforce the need to screen for urinary abnormalities in family members of patients affected by HSP nephritis to identify a silent IgA nephropathy. PMID:24782055

  9. [Clinico-pathological features and outcome in adult patients with Henoch-Schönlein purpura nephritis].

    PubMed

    Tsuruta, Yuki; Takei, Takashi; Takano, Mari; Sawara, Yukako; Aoki, Akiko; Eguchi, Aya; Kojima, Chiari; Moriyama, Takahito; Itabashi, Mitsuyo; Sugiura, Hidekazu; Tsukada, Misao; Ogawa, Tetsuya; Yoshida, Takumi; Uchida, Keiko; Tsuchiya, Ken; Nitta, Kosaku

    2010-01-01

    We examined the data of 24 patients with Henoch-Schönlein purpura nephritis (HSPN) over a 5-year follow-up period. Proteinuria, sediment RBC and CRP significantly decreased between the time of diagnosis and the end of the 5-year period. In the steroid usage group (n = 16), proteinuria was significantly higher, and crescent formation was significant higher at the time of diagnosis than in the non-steroid usage group (n = 8). However, there was no significant difference in the decrease in eGFR from the baseline at the end of the 5-year period between the two groups. Furthermore, to clarify the factors influencing the risk of renal function deterioration, we divided the patients into two groups, the (delta eGFR/pre eGFR) <0.25 group (n = 13) and (delta eGFR/pre eGFR) >0.25 group (n = 11), and compared the clinico-pathophysiological characteristics between the two groups. In the (delta eGFR/pre eGFR) >0.25 group, the ratio of glomerular obsolescence at the time of diagnosis was significantly higher than in the (delta eGFR/pre eGFR) <0.25 group. Glomerular obsolescence was identified as an independent risk factor for renal function deterioration. In this study, the prognosis of HSPN was related to glomerular obsolescence rather than to the disease activity. It may be necessary to consider the decrease in nephrons, in accordance with non-immunological glomerular obsolescence, in addition to immunological treatment to clarify the prognosis. PMID:20166542

  10. Mycophenolate mofetil plus prednisone for inducing remission of Henoch-Schönlein purpura nephritis: a retrospective study*

    PubMed Central

    Han, Fei; Chen, Liang-liang; Ren, Ping-ping; Le, Jing-yun; Choong, Pei-jing; Wang, Hong-ju; Xu, Ying; Chen, Jiang-hua

    2015-01-01

    Objective: The treatment of Henoch-Schönlein purpura (HSP) with moderate proteinuria remains controversial. We retrospectively analyzed the efficacy of immune suppressants, with a particular emphasis on mycophenolate mofetil (MMF). Methods: Ninety-five HSP patients with moderate proteinuria (1.0–3.5 g/24 h) after at least three months of therapy with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) were divided into three groups: an MMF group (n=33) that received MMF 1.0–1.5 g/d combined with prednisone (0.4–0.5 mg/(kg·d)), a corticosteroid (CS) group (n=31) that received full-dose prednisone (0.8–1.0 mg/(kg·d)), and a control group (n=31). Patients in the MMF and CS groups continued to take ACEI or ARB at the original dose. The patients in the control group continued to take ACEI or ARB but the dose was increased by (1.73±0.58)-fold. The patients were followed up for 6–78 months (median 28 months). Results: The baseline proteinuria was higher in the MMF group ((2.1±0.9) g/24 h) than in the control group ((1.6±0.8) g/24 h) (P=0.039). The proteinuria decreased significantly in all groups during follow-up, but only in the MMF group did it decrease significantly after the first month. At the end of follow-up, the proteinuria was (0.4±0.7) g/24 h in the MMF group and (0.4±0.4) g/24 h in the CS group, significantly lower than that in the control group ((0.9±1.1) g/24 h). The remission rates in the MMF group, CS group, and control group were respectively 72.7%, 71.0%, and 48.4% at six months and 72.7%, 64.5%, and 45.2% at the end of follow-up. The overall number of reported adverse events was 17 in the MMF group, 30 in the CS group, and 6 in the control group (P<0.001). Conclusions: MMF with low-dose prednisone may be as effective as full-dose prednisone and tend to have fewer adverse events. Therefore, it is probably superior to conservative treatments of adult HSP patients with moderate proteinuria. PMID:26365119

  11. Joint effusions and purpura in multiply-transfused adult beta-thalassemia- clinical pointers to diagnosis of scurvy.

    PubMed

    Prakash, A; Pandey, A K

    2013-01-01

    Periodic transfusions and effective chelation have ensured that thalassemics survive in to adulthood but their life is punctuated by peculiar problems in adulthood. Three cases of scurvy are being reported presenting uniquely as purpura, right hip joint effusion and right knee joint effusion with haemorrhage in prepatellar and retropatellar bursae, respectively over an 18 month period (2009-2010). The first two cases did give a history of gum bleed. None had any coagulation disturbance or transfusion-transmitted infections or connective tissue disorder. All the three cases responded dramatically to vitamin C supplementation. It is imperative to keep in mind that recurrent blood transfusions are associated with a state of subclinical vitamin C deficiency and overt scurvy may manifest as cumulative number of transfusions increase, as in adult thalassemics. PMID:24899338

  12. Penile Skin Involvement as the First Presentation of Henoch-Schonlein Purpura Report of Nine Cases and Review of Literature

    PubMed Central

    Paydary, Koosha; Emamzadeh Fard, Sahra; Mahboubi, Amir Hassan; Ziaee, Vahid; Moradinejad, Mohammad Hassan; Kajbafzadeh, Abdol-Mohammad

    2015-01-01

    Introduction: Involvement of penis is a rare presentation in henoch-schonlein purpura (HSP). The presentations are mainly due to the deposition of immunoglobulin A (IgA) into the vessel walls. In this report, we present the clinical history of nine HSP cases that presented with penile skin involvement. Case Presentation: All patients were referred in the acute phase of HSP. Penile skin involvement was evident as erythema, edema, ecchymosis, or induration of prepuce and/or penile shaft, that appeared simultaneously with skin rash in seven patients. Gastrointestinal involvement was positive in six patients. Patients were treated with steroids and follow up visits were normal except for one patient that developed crescentic glomerulonephritis. Conclusions: We present nine cases of HSP with penile involvement in order to indicate another rare aspect of HSP and its possible complications as well as its appropriate treatment. PMID:26396696

  13. A higher frequency of CD4(+)CXCR5(+) T follicular helper cells in patients with newly diagnosed Henoch-Schönlein purpura nephritis.

    PubMed

    Zhang, Zhihui; Zhao, Songchen; Zhang, Li; Crew, Rebecca; Zhang, Nan; Sun, Xiguang; Jiang, Yanfang

    2016-03-01

    T follicular helper (TFH) cells play an important role in the humoral immune responses. The aim of this study was to examine the frequency of different subsets of CD4(+)CXCR5(+) TFH cells and B cells in patients with new-onset Henoch-Schönlein purpura nephritis (HSPN). The numbers of different subsets of CD4(+)CXCR5(+) TFH cells, B cells and the constituents of serum cytokines were detected in a total of 25 patients with newly diagnosed HSPN before and after treatment, and in 14 healthy controls (HC). The potential connection of these cells with the clinical characteristics in HSPN patients was analyzed. The numbers of circulating CD4(+)CXCR5(+), CD4(+)CXCR5(+)ICOS(+) and CD4(+)CXCR5(+)PD-1(+) TFH cells, CD86(+)CD19(+), CD38(+)CD19(+) B cells and serum IL-2, IL-4, IL-17A, IL-21 and IFN-? were significantly higher in HSPN patients (p<0.05) than in HC. Before and after treatment the numbers of CD4(+)CXCR5(+) TFH cells were negatively correlated with the values of eGFR (r=-0.7162, p<0.05; r=-0.732, p<0.05, respectively). Similarly the numbers of CD4(+)CXCR5(+)PD-1(+) TFH cells were negatively correlated with 24-h urinary proteins (r=-0.4013, p<0.05; r=-0.7857, p<0.05, respectively), and the numbers of CD4(+)CXCR5(+)ICOS(+) TFH cells were positively correlated with the levels of serum IL-21 (r=0.5186, p<0.05; r=0.8503, p<0.05, respectively) and 24-h urinary protein (r=0.6045, p<0.05; r=0.833, p<0.05, respectively) in these patients, regardless of treatment. Following treatment the numbers of CD4(+)CXCR5(+), CD4(+)CXCR5(+)PD-1(+), and CD4(+)CXCR5(+)ICOS(+) TFH cells, as well as serum levels of IL-21 were significantly reduced, however IL-4 levels were noticeably increased (p<0.05). A higher frequency of circulating CD4(+)CXCR5(+) TFH cells existed in patients with HSPN and may be a viable therapeutic target. PMID:26774213

  14. Haematology and neurology

    PubMed Central

    Austin, Steven; Cohen, Hannah; Losseff, Nick

    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. PMID:17369588

  15. Henoch-Schönlein purpura (HSP) and high-dose immunoglobulin treatment in patient with familiar prostatic adenocarcinoma.

    PubMed

    Sobieszcza?ska, Ma?gorzata; Tubek, S?awomir; Poplicha, Dagmara; Grabelus, Anna; Pawe?czak, Jacek

    2014-01-01

    A 52-y old man was admitted to our Department because of abdominal pains and diarrhea with fresh blood, with concomitant purpura over the whole body and edema of the both tarsal joints. The medical history of the patient included skin changes of similar character identified once 10-12 y before. The family history revealed prostate cancer (brother and father) and pulmonary carcinoma (mother and mother's sister). An administration of immunoglobulins in the course of HSP is a non-standard clinical procedure and in case of our patient--clinically effective. In the literature, we have found only few articles about intravenous immunoglobulin treatment for acute, adult-onset HSP and only one article about GI bleeding from colonic ecchymoses in HSP. In these cases HSP wasn't associated with prostate cancer. In the first article, authors had seen dramatic responses to intravenous immunoglobulin, like in the case presented by us. IV-IG acts as an immunomodulator by suppression of antibody production, Fc-receptor blockade and anti-idiotypic reaction. In our case, the last two mechanisms could be perceived as favorable effects of IV-IG. PMID:24231833

  16. 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

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

    SciTech Connect

    Beale, M.G.; 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.

  18. 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. PMID:26045740

  19. Association of the paired box 2 gene polymorphism with the susceptibility and pathogenesis of Henoch?Schönlein purpura in children.

    PubMed

    Chen, Jing; Fang, Xiangling; Dang, Xiqiang; Wu, Xiaochuan; Yi, Zhuwen

    2015-03-01

    The present study aimed to investigate the distribution of paired box 2 (PAX2) gene polymorphisms in healthy populations and in patients with Henoch?Schönlein purpura (HSP), focusing on the association between PAX2 gene polymorphisms and the susceptibility and clinical characteristics of HSP. Genomic DNA was extracted from the peripheral venous blood of 100 healthy children (mean age: 5 ± 1.9 years) and 118 children with HSP (mean age: 10.2 ± 2.3 years). Polymerase chain reaction (PCR) was used to amplify exons 1?12 of the PAX2 gene. Denaturing high performance liquid chromatography and DNA sequencing analysis were conducted for screening of mutations in the PAX2 gene in the PCR products. No genetic polymorphism of the PAX2 gene was identified in exons 1?7, 9, 10 or 12. Two single nucleotide polymorphisms (SNPs), which presented as complete linkage haplotype 798C>T/909A>C, were identified in exon 8. An SNP (1164T>A) was also identified in exon 11. No significant difference in the allele and genotype frequency distribution of exon 8 (798C>T) or 11 (1164T>A) of the PAX2 gene was identified between the HSP and control groups (P>0.05). However, the frequency of the PAX2 heterozygous genotype 798C>T in the HSP with nephritis (HSPN) group was significantly higher than those in the controls and in the HSP without nephritis group (P<0.05). Furthermore, no significant correlation was identified between the PAX2 gene exon 8 polymorphism (798 C>T) and the renal pathology of children with HSPN. An SNP (1164T>A) was identified in exon 11. The PAX2 heterozygous genotype 798C>T did not increase susceptibility to HSP, however, it may be used clinically as a screening indicator for HSP in children with a high risk of renal involvement. PMID:25385517

  20. Targeting intracellular targets.

    PubMed

    Panyam, Jayanth; Labhasetwar, Vinod

    2004-07-01

    Many therapeutic agents have intracellular compartments as their site of action. Targeted delivery of these agents to their specific intracellular targets could result in enhanced therapeutic efficacy and reduced toxicity. Various carriers have been shown useful in targeted delivery of different classes of therapeutic agents. Among these carriers, biodegradable nanoparticles formulated from biocompatible polymers poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) have shown the potential for sustained intracellular delivery of different therapeutic agents. In this review, we discuss different intracellular targets, barriers to intracellular delivery, mechanism and pathways of intracellular delivery, and various carriers and approaches that have been investigated for intracellular drug delivery. PMID:16305387

  1. Association between toll-like receptor 6 expression and auxiliary T cells in the peripheral blood of pediatric patients with allergic purpura

    PubMed Central

    CHANG, HONG; CAO, YONGXIAN; LIN, YI; ZHU, HAIYAN; FU, YUAN; CHEN, XIUXIA; ZHANG, QIUYE

    2015-01-01

    The aim of the present study was to investigate the correlations between toll-like receptor 6 (TLR6) expression in the peripheral blood mononuclear cells (PBMCs) and auxiliary T cells of children with purpura. A total of 42 children with acute Henoch-Schönlein purpura (HSP) were selected for the study, and a further 30 healthy children were selected as a control group. Enzyme-linked immunosorbent assays were performed to detect the levels of plasma interferon (IFN)-?, interleukin (IL)-4 and IL-17, and flow cytometry was performed to detect the TLR6 protein expression levels in PBMCs. The plasma levels of IL-4, IFN-? and IL-17 in the HSP group were significantly higher compared with those in the normal control group. TLR6 protein expression was significantly increased in the PBMCs of the HSP patients. The TLR6 protein expression levels in the monocytes of the HSP group significantly positively correlated with the serum IL-4 and IL-17 levels, but not with the serum levels of IFN-?. Therefore, the results of the present study suggest that the activation of TLR6 may be involved in the immunopathogenesis of HSP, and that the activated TLR6 may mediate this process by upregulating the immune responses of type 2 T helper (Th2) and Th17 cells. PMID:26622521

  2. PlayStation purpura.

    PubMed

    Robertson, Susan J; Leonard, Jane; Chamberlain, Alex J

    2010-08-01

    A 16-year-old boy presented with a number of asymptomatic pigmented macules on the volar aspect of his index fingers. Dermoscopy of each macule revealed a parallel ridge pattern of homogenous reddish-brown pigment. We propose that these lesions were induced by repetitive trauma from a Sony PlayStation 3 (Sony Corporation, Tokyo, Japan) vibration feedback controller. The lesions completely resolved following abstinence from gaming over a number of weeks. Although the parallel ridge pattern is typically the hallmark for early acral lentiginous melanoma, it may be observed in a limited number of benign entities, including subcorneal haematoma. PMID:20695869

  3. Henoch-Schonlein Purpura

    MedlinePLUS

    ... than 5% of patients with HSP develop progressive renal insufficiency. HSP can be mimicked by other forms of ... progress from hematuria (blood in the urine) to renal insufficiency (decreased kidney function). HSP patients who experience this ...

  4. Sputter target

    DOEpatents

    Gates, Willard G.; Hale, Gerald J.

    1980-01-01

    The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

  5. Elevated levels of antibodies against phosphatidylserine/prothrombin complex and/or cardiolipin associated with infection and recurrent purpura in a child: a forme fruste of antiphospholipid syndrome?

    PubMed

    Kinoshita, Yuri; Mayumi, Nobuko; Inaba, Motoyuki; Igarashi, Touru; Katagiri, Ichigen; Kawana, Seiji

    2015-01-01

    Antiphospholipid syndrome is an autoimmune disorder characterized by the occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy, in the presence of anti-phospholipid antibodies. The diagnosis of antiphospholipid syndrome is usually established based on clinical and laboratory findings by strictly following the 2006 Sapporo classification. However, the diagnosis remains challenging owing to the ongoing debates on the serological criteria. We report a case we describe as forme fruste antiphospholipid syndrome in which these criteria were not fulfilled. Purpura appeared repeatedly in a female infant starting from the age of 6 months and following episodes of upper respiratory infections and vaccinations. The levels of anti-cardiolipin IgG antibodies and anti-phosphatidylserine/prothrombin complex antibodies were elevated in accordance with these events. Histopathological evaluation revealed multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection has long been associated with antiphospholipid syndrome, and anti-phosphatidylserine/prothrombin antibodies are considered a new marker for the diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome should be considered even if the antiphospholipid syndrome diagnostic criteria are not completely fulfilled, especially in the presence of elevated levels of anti-phosphatidylserine/prothrombin antibodies and known preceding infections. PMID:26436970

  6. Henoch-Schönlein purpura following high-voltage electric burn injury: A case report and review of the literature

    PubMed Central

    DUAN, XUNHONG; YU, DONGQI; YU, CHANGLONG; WANG, BIAO; GUO, YIBIN

    2016-01-01

    Henoch-Schönlein Purpura (HSP) is a systemic vasculitis of unknown cause, with immune-mediated inflammation of the small vessels, which is characterized by a series of clinical symptoms, such as purpuric rash, colicky abdominal pain, arthritis and acute glomerulonephritis. Twenty-one days following a high-voltage electrical burn injury, a 40-year-old man developed classic clinical symptoms of HSP, including purpuric rash on bilateral lower extremities and abdominal pain. The patient was diagnosed with HSP associated with high-voltage burn injury, which is an extremely rare phenomenon. The diagnosis was based on the clinical manifestations of purpuric rash, abdominal pain and arthralgia, as well as the findings of laboratory examinations [increased levels of serum immunoglobulin A (11.6g/l) and complements C3 (9.6 g/l) and C4 (7.6 g/l), and a positive fecal occult blood test]. The patient was treated with antihistamines (loratadine tablets; 10 mg/day), anti-inflammatory medication (methylprednisolone sodium succinate; 40 mg/day) and oral omeprazole magnesium. The symptoms gradually decreased within 2 weeks from treatment and no abnormality was observed at the 3-, 6- and 12-month follow-ups. In patients who have suffered an electrical burn injury, this autoimmune disease may be caused by long-term inflammation. Therefore, examination of the liver and kidney functions of such patients is important in order to decrease the risk of post-traumatic immune system dysfunction. PMID:26893643

  7. ISAC targets

    NASA Astrophysics Data System (ADS)

    Dombsky, M.; Kunz, P.

    2014-01-01

    The TRIUMF-ISAC radioactive ion beam facility was designed and constructed to allow irradiation of thick targets with up to 100 A proton beam intensities. Since beginning operation in 1998, beam intensities on ISAC targets have progressively increased toward the 100 A design limit. Routine operation with p + intensities up to 75 A is currently possible for both refractory metal target materials and for composite metal carbide materials; full 99 A p + intensity has been achieved for Nb foil target material. Consideration must be given to the beam power deposition, the power dissipation and the limiting temperature criteria of each target material. Increased beam power dissipation has been achieved by modifying target materials and target containers. Increasing irradiation currents have produced benefits, drawbacks and unexpected results for ISOL operations.

  8. Targeted Audio

    NASA Astrophysics Data System (ADS)

    Olszewski, Dirk

    Targeted audio aims at creating personal listening zones by utilizing adequate measurements. A person inside this listening zone shall be able to perceive acoustically submitted information without disturbing other persons outside the desired listening zone. In order to fulfill this demand, the use of a highly directional audible sound beam is favored. The sound beam shall be aimed at the respective listening zone target, thus implicating the expression targeted audio.

  9. 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

  10. Targeted metabolomics.

    PubMed

    Roberts, Lee D; Souza, Amanda L; Gerszten, Robert E; Clish, Clary B

    2012-04-01

    The metabolome is the terminal downstream product of the genome and consists of the total complement of all the low-molecular-weight molecules (metabolites) in a cell, tissue, or organism. Metabolomics aims to measure a wide breadth of small molecules in the context of physiological stimuli or disease states. Metabolomics methodologies fall into two distinct groups: untargeted metabolomics, an intended comprehensive analysis of all the measurable analytes in a sample including chemical unknowns, and targeted metabolomics, the measurement of defined groups of chemically characterized and biochemically annotated metabolites. The methodologies considered in this unit focus on the processes of conducting targeted metabolomics experiments, and the advantages of this general approach are highlighted herein. This unit outlines procedures for extracting nitrogenous metabolites (including amino acids), lipids, and intermediary metabolites (including TCA cycle oxoacids) from blood plasma. Specifically, protocols are described for analyzing these metabolites using targeted metabolomics experiments based on liquid chromatography-mass spectrometry. PMID:22470063

  11. Targeted Metabolomics

    PubMed Central

    Roberts, Lee D.; Souza, Amanda L.; Gerszten, Robert E.; Clish, Clary B.

    2012-01-01

    The metabolome is the terminal downstream product of the genome and consists of the total complement of all the low molecular weight molecules (metabolites) in a cell, tissue or organism. Metabolomics aims to measure a wide breadth of small molecules in the context of physiological stimuli or in disease states. Metabolomics methodologies fall into two distinct groups; untargeted metabolomics, an intended comprehensive analysis of all the measurable analytes in a sample including chemical unknowns, and targeted metabolomics, the measurement of defined groups of chemically characterized and biochemically annotated metabolites. The methodologies considered in this unit focus on the processes of conducting targeted metabolomics experiments, and the advantages of this general approach are highlighted herein. This unit outlines the procedures for extracting nitrogenous metabolites, including the amino acids, lipids, and intermediary metabolites, including the TCA cycle oxoacids, from blood plasma. Specifically, protocols for the analysis of these metabolites using liquid chromatography-mass spectrometry-based targeted metabolomics experiments is discussed. PMID:22470063

  12. Tackling Targets.

    ERIC Educational Resources Information Center

    Further Education Unit, London (England).

    This document is designed to help British training and enterprise councils (TECs) and further education (FE) colleges develop and implement strategies for achieving the National Targets for Education and Training (NTET), which were developed by the Confederation of British Industry in 1992 and endorsed by the British government. The findings from…

  13. Target: Lifestyle.

    ERIC Educational Resources Information Center

    Poehlman, Eric T.

    1985-01-01

    "Target: Lifestyle" is a physical education curriculum adopted by Detroit Country Day School which incorporates instruction in nutrition, physical fitness, first aid, and lifetime sports. This curriculum aims to influence student attitudes and lifestyles in health and physical fitness. Four levels of instruction are described. (DF)

  14. Target assembly

    DOEpatents

    Lewis, Richard A. (Falls Church, VA)

    1980-01-01

    A target for a proton beam which is capable of generating neutrons for absorption in a breeding blanket includes a plurality of solid pins formed of a neutron emissive target material disposed parallel to the path of the beam and which are arranged axially in a plurality of layers so that pins in each layer are offset with respect to pins in all other layers, enough layers being used so that each proton in the beam will strike at least one pin with means being provided to cool the pins. For a 300 mA, 1 GeV beam (300 MW), stainless steel pins, 12 inches long and 0.23 inches in diameter are arranged in triangular array in six layers with one sixth of the pins in each layer, the number of pins being such that the entire cross sectional area of the beam is covered by the pins with minimum overlap of pins.

  15. Information about TTP-HUS

    MedlinePLUS

    ... the kidneys, heart, and brain. T is for Thrombocytopenic, a term describing low platelet counts. Platelets are blood cells that are needed to stop bleeding. In TTP, they are used up in the abnormal clots that occur throughout the body. P is for Purpura, a term describing the bruises and the small ...

  16. Immune thrombocytopenia associated with consumption of tonic water

    PubMed Central

    2015-01-01

    Thrombocytopenic purpura can develop from an induced antibody response that destroys platelets. Megakaryocyte production may also play a role. Although the inciting antigen is usually not identified, it is important to consider medications. This article presents the case of a man who developed sudden onset of severe thrombocytopenia associated with the ingestion of quinine-containing tonic water. PMID:25829658

  17. Targeting metastasis.

    PubMed

    Steeg, Patricia S

    2016-03-24

    Tumour metastasis, the movement of tumour cells from a primary site to progressively colonize distant organs, is a major contributor to the deaths of cancer patients. Therapeutic goals are the prevention of an initial metastasis in high-risk patients, shrinkage of established lesions and prevention of additional metastases in patients with limited disease. Instead of being autonomous, tumour cells engage in bidirectional interactions with metastatic microenvironments to alter antitumour immunity, the extracellular milieu, genomic stability, survival signalling, chemotherapeutic resistance and proliferative cycles. Can targeting of these interactions significantly improve patient outcomes? In this Review preclinical research, combination therapies and clinical trial designs are re-examined. PMID:27009393

  18. Accelerator target

    DOEpatents

    Schlyer, D.J.; Ferrieri, R.A.; Koehler, C.

    1999-06-29

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression. 5 figs.

  19. Accelerator target

    DOEpatents

    Schlyer, David J.; Ferrieri, Richard A.; Koehler, Conrad

    1999-01-01

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression.

  20. Photolocalized purpura during levofloxacin therapy.

    PubMed

    Rubegni, Pietro; Feci, Luca; Pellegrino, Michele; Fimiani, Michele

    2012-04-01

    Side-effects associated with levofloxacin treatment include phototoxicity, hypersensitivity and skin disorders. Purpuric eruptions have rarely been reported. We describe the case of a 75-year-old woman who was prescribed a 15-day course of levofloxacin (500 mg twice a day) for hemorrhagic cystitis. On exposure to sunlight, the patient developed a pruritic purpuric eruption on the lower extremities. The acute reaction differed from a classical sunburn, manifesting as confluent petechiae limited to sun-exposed areas and accompanied by pruritus. This was a rare case of solar capillaritis. Purpuric eruptions on photoexposed skin should be considered another unusual side effect of levofloxacin. PMID:22409715

  1. 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.

  2. Targeted Cancer Therapies

    MedlinePLUS

    ... spread of cancer by interfering with specific molecules ("molecular targets") that are involved in the growth, progression , ... in several ways: Targeted therapies act on specific molecular targets that are associated with cancer, whereas most ...

  3. Clinical uses of radiolabeled platelets

    SciTech Connect

    Datz, F.L.; Christian, P.E.; Baker, W.J.

    1985-12-01

    Platelets were first successfully radiolabeled in 1953. At that time, investigators were primarily interested in developing a technique to accurately measure platelet life span in both normal and thrombocytopenic patients. Studies using platelets labeled with /sup 51/Cr have shown shortened platelet survival times in a number of diseases including idiopathic thrombocytopenic purpura, coronary artery disease, and diabetes mellitus. More recently, labels such as /sup 111/In have been developed that allow in vivo imaging of platelets. Indium-111 platelets are being used to better understand the pathophysiology of atherosclerosis, thrombophlebitis, pulmonary embolism and clotting disorders, and to improve the clinical diagnosis of these diseases.

  4. 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.

  5. Polarized internal target apparatus

    DOEpatents

    Holt, R.J.

    1984-10-10

    A polarized internal target apparatus with a polarized gas target of improved polarization and density (achieved by mixing target gas atoms with a small amount of alkali metal gas atoms, and passing a high intensity polarized light source into the mixture to cause the alkali metal gas atoms to become polarized which interact in spin exchange collisions with target gas atoms yielding polarized target gas atoms) is described.

  6. Organelle targeting: third level of drug targeting

    PubMed Central

    Sakhrani, Niraj M; Padh, Harish

    2013-01-01

    Drug discovery and drug delivery are two main aspects for treatment of a variety of disorders. However, the real bottleneck associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and innumerable other side effects as well as higher dosage requirement for efficacy. An attractive strategy to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target cells, but more importantly, into the targeted organelle, ie, to its intracellular therapeutic active site. This would ensure improved efficacy and minimize toxicity. Cancer chemotherapy today faces the major challenge of delivering chemotherapeutic drugs exclusively to tumor cells, while sparing normal proliferating cells. Nanoparticles play a crucial role by acting as a vehicle for delivery of drugs to target sites inside tumor cells. In this review, we spotlight active and passive targeting, followed by discussion of the importance of targeting to specific cell organelles and the potential role of cell-penetrating peptides. Finally, the discussion will address the strategies for drug/DNA targeting to lysosomes, mitochondria, nuclei and Golgi/endoplasmic reticulum. PMID:23898223

  7. Magnetically attached sputter targets

    DOEpatents

    Makowiecki, Daniel M. (Livermore, CA); McKernan, Mark A. (Livermore, CA)

    1994-01-01

    An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly.

  8. Magnetically attached sputter targets

    DOEpatents

    Makowiecki, D.M.; McKernan, M.A.

    1994-02-15

    An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material is described. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly. 11 figures.

  9. Human target acquisition performance

    NASA Astrophysics Data System (ADS)

    Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

    2012-06-01

    The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

  10. Targeted therapies for cancer

    MedlinePLUS

    ... Colon cancer Skin cancer Lung cancer Prostate Other cancers that may be treated with targeted therapies include brain, bone, kidney, lymphoma, stomach, and many others. Your provider will decide whether targeted ...

  11. Molecular Targets Laboratory

    Cancer.gov

    Group Mission: Develops, adapts, evaluates, and applies novel screening assays, protocols and emerging technologies for molecular target validation, molecularly targeted lead discovery and research; Provides screening support for bioassay-guided lead isol

  12. Target Heart Rates

    MedlinePLUS

    ... 60 - 100 beats per minute for well-trained athletes is 40 - 60 beats per minute. Hittin’ the Target Now you’re ready to determine your target training heart rate. As you exercise, periodically: Take your pulse ...

  13. 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.

  14. 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.

  15. Kepler Target Pixel Files

    NASA Astrophysics Data System (ADS)

    Thompson, Susan E.; McCauliff, S.; Bryson, S.; Still, M.; van Cleve, J.; Dotson, J.; Twicken, J.; Klaus, T.; Cote, M.; Fanelli, M.

    2011-01-01

    In early 2011, the Kepler Mission will make available the pixel data for all observed targets, in addition to the aperture photometry light curves currently provided at the Multi-mission Archive at STScI (MAST). These target pixel files will contain images of the calibrated flux, the subtracted background, and the removed cosmic rays for the target at each cadence. Certain targets, such as highly variable stars, non-stellar targets, or saturated targets, require an analysis beyond fixed, optimal aperture photometry in order to retrieve all the information from the data. For a few cases we demonstrate the utility of the target pixel files in understanding the quality of the data and in performing specialized aperture photometry. Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA, Science Mission Directorate.

  16. Magnetized Target Fusion: Improving the plasma target

    NASA Astrophysics Data System (ADS)

    Intrator, T.; Magnetized Target Fusion Collaboration

    2011-10-01

    Magneto Inertial Fusion (MIF) inertial adiabatic compression of a plasma fuel target takes advantage of embedded magnetic field to reduce thermal conduction and enhance alpha-particle heating. Magnetized Target Fusion (MTF) is a subset of MIF, requiring target plasma formation plus ejection into a solid flux conserving compressor shell or liner that implodes and compresses a plasma target. The liner has much larger mass than the compressed fuel, which increases the dwell time because it scales as the square root of the total mass. It appears possible to exceed the typical figure of merit eta*G > 10 which is the product of (high) driver efficiency eta and (small) fusion gain G. We describe our efforts to improve the plasma target lifetime by using plasma guns. We also show recent data including experimental engineering test shots in a collaboration with Kirtland Air Force Research Laboratory to realize a physics demonstration of MTF. DOE, Office of Science, Office of Fusion Energy Sciences, under LANS Contract No. DE-AC52-06NA25396.

  17. Bar coded retroreflective target

    DOEpatents

    Vann, Charles S.

    2000-01-01

    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.

  18. Severe Thrombotic Complication of Eltrombopag in a Cirrhotic Patient

    PubMed Central

    Wheeler, David S.; Varadi, Gabor; Feyssa, Eyob

    2016-01-01

    We present a patient with hepatitis C virus (HCV) and cirrhosis who was treated with eltrombopag for idiopathic thrombocytopenic purpura and was incidentally found to have a right atrial thrombus with extension into the left internal jugular vein. Eltrombopag was discontinued and the patient was treated with thrombectomy and anticoagulation. Given the proposed use of eltrombopag in HCV-associated thrombocytopenia, we advise caution when treating cirrhotics who are at higher intrinsic risk of thrombosis. PMID:26958566

  19. Severe Thrombotic Complication of Eltrombopag in a Cirrhotic Patient.

    PubMed

    Baumann, Alexandra J; Wheeler, David S; Varadi, Gabor; Feyssa, Eyob

    2016-01-01

    We present a patient with hepatitis C virus (HCV) and cirrhosis who was treated with eltrombopag for idiopathic thrombocytopenic purpura and was incidentally found to have a right atrial thrombus with extension into the left internal jugular vein. Eltrombopag was discontinued and the patient was treated with thrombectomy and anticoagulation. Given the proposed use of eltrombopag in HCV-associated thrombocytopenia, we advise caution when treating cirrhotics who are at higher intrinsic risk of thrombosis. PMID:26958566

  20. Thrombocytopenia-associated multi-organ failure caused by diabetic ketoacidosis.

    PubMed

    Alsaied, Tarek; Goldstein, Stuart L; Kaddourah, Ahmad; Poynter, Sue E

    2016-03-01

    Thrombocytopenia-associated multi-organ failure (TAMOF) is an increasingly reported entity in the pediatric intensive care unit. The clinical presentation is similar to thrombotic thrombocytopenic purpura, but with no evidence of hemolysis and no schistocytes on peripheral smear. We report a case of TAMOF induced by diabetic ketoacidosis and treated with therapeutic plasma exchange (TPE). Early diagnosis and initiation of TPE significantly decrease the morbidity associated with TAMOF. PMID:26712331

  1. Acquired bleeding disorders.

    PubMed

    Hurwitz, Alisheba; Massone, Richard; Lopez, Bernard L

    2014-08-01

    Emergency medicine practitioners treat bleeding patients on a regular basis. Disorders of hemostasis are an additional challenge in these patients but can be assessed and managed in a systematic fashion. Of particular importance to the emergency clinician are the iatrogenic causes of abnormal hemostasis. Other acquired causes of abnormal hemostasis include renal disease, immune thrombocytopenia, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acquired coagulation factor inhibitors, acute traumatic coagulopathy, liver disease, and disseminated intravascular coagulopathy. PMID:25060257

  2. In planta gene targeting

    PubMed Central

    Fauser, Friedrich; Roth, Nadine; Pacher, Michael; Ilg, Gabriele; Sánchez-Fernández, Rocío; Biesgen, Christian; Puchta, Holger

    2012-01-01

    The development of designed site-specific endonucleases boosted the establishment of gene targeting (GT) techniques in a row of different species. However, the methods described in plants require a highly efficient transformation and regeneration procedure and, therefore, can be applied to very few species. Here, we describe a highly efficient GT system that is suitable for all transformable plants regardless of transformation efficiency. Efficient in planta GT was achieved in Arabidopsis thaliana by expression of a site-specific endonuclease that not only cuts within the target but also the chromosomal transgenic donor, leading to an excised targeting vector. Progeny clonal for the targeted allele could be obtained directly by harvesting seeds. Targeted events could be identified up to approximately once per 100 seeds depending on the target donor combination. Molecular analysis demonstrated that, in almost all events, homologous recombination occurred at both ends of the break. No ectopic integration of the GT vector was found. PMID:22529367

  3. Oxide targets for Gammasphere

    NASA Astrophysics Data System (ADS)

    Greene, John P.; Lister, Kim; Fischer, Susan

    2006-05-01

    We here report on recent experiments at GAMMASPHERE employing highly inverse, near-barrier reactions with silicon dioxide targets and use the Fragment Mass Analyzer (FMA) to collect the recoils. The 16O( 58Ni,2n) 72Kr reaction was studied with beams of 220 MeV 58Ni in excess of 15 pnA. Relatively few stable beam and target combinations are available to populate excited states in 72Kr, and the small cross sections of these reactions necessitate the use of targets that can withstand high intensity beam currents. A variety of oxygen containing targets were produced, with those made of silicon dioxide performing best. Over a period of 24 h of irradiation the oxygen content in these targets monotonically declined to about 1/3 of the original value. The silicon content did not appear to change. By inserting new sets of targets each 18-h-cycle an impressive data set was collected.

  4. Effective neutron targets

    SciTech Connect

    Gao, H.

    1997-07-01

    Because of the lack of a free neutron target, deuterium targets have been used extensively in studying the neutron structure. The unique spin structure of the {sup 3}He ground state wave function and the recent developments in laser technologies made polarized {sup 3}He targets widely used in many experiments from neutron electromagnetic form factor studies to nucleon spin structure function measurements at all major electron accelerator facilities. In this talk, the current status of the polarized {sup 3}He targets will be reviewed. The author will focus on neutron electromagnetic form factor studies using polarized {sup 3}He targets. The polarized nucleon spin structure function measurements using polarized {sup 3}He targets will also be discussed.

  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. Autonomous target screeners

    NASA Astrophysics Data System (ADS)

    Aggarwal, R. K.; Geokezas, M.; Soland, D. E.

    1980-11-01

    The basic functions of an autonomous target screener are: segmentation, feature generation, classification (detection/recognition), and symbol generation. Image segmentation is the function by which the image is segmented in background and objects of interest. The image information within these objects of interest is processed to generate a set of features which characterize the targets of interest. The classification function utilizes statistical/syntactic classifier for detection (target vs. clutter decision) and recognition (truck, tank, APC, etc.). A symbol indicating the position and type of target is displayed on the monitor for cueing purposes.

  7. 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

  8. Targeted anti bacterial therapy.

    PubMed

    Yacoby, Iftach; Benhar, Itai

    2007-09-01

    The increasing development of bacterial resistance to traditional antibiotics has reached alarming levels, thus necessitating a strong need to develop new antimicrobial agents. These new antimicrobials should possess novel modes of action and/or different cellular targets compared with the existing antibiotics. As a result, new classes of compounds designed to avoid defined resistance mechanisms are undergoing pre clinical and clinical evaluation. Microbial and phage genomic sequencing are now being used to find previously unidentified genes and their corresponding proteins. In both traditional and newly developed antibiotics, the target selectivity lies in the drug itself, in its ability to affect a mechanism that is unique to prokaryotes. As a result, a vast number of potent agents that, due to low selectivity, in addition to the pathogen also affect the eukaryote host have been excluded from use as therapeutics. Such compounds could be re-considered for clinical use if applied as part of a targeted delivery platform where the drug selectivity is replaced by target-selectivity borne by the targeting moiety. With a large number of antibodies and antibody-drug conjugates already approved or near approval as cancer therapeutics, targeted therapy is becoming increasingly attractive and additional potential targeting moieties that are non-antibody based, such as peptides, non-antibody ligand-binding proteins and even carbohydrates are receiving increasing attention. Still, targeted therapy is mostly focused on cancer, with targeted anti bacterial therapies being suggested only very recently. This review will focus in the various methods of antimicrobial targeting, by systemic and local application of targeted antimicrobial substances. PMID:17897058

  9. Target visibility for multiple maneuvering target tracking

    NASA Astrophysics Data System (ADS)

    Sabordo, Madeleine G.; Aboutanios, Elias

    2015-05-01

    We present a recursion of the probability of target visibility and its applications to analysis of track life and termination in the context of Global Nearest Neighbour (GNN) approach and Probability Hypothesis Density (PHD) filter. In the presence of uncertainties brought about by clutter; decisions to retain a track, terminate it or initialise a new track are based on probability, rather than on distance criterion or estimation error. The visibility concept is introduced into a conventional data-association-oriented multitarget tracker, the GNN; and a random finite set based-tracker, the PHD filter, to take into account instances when targets become invisible or occluded by obstacles. We employ the natural logarithmof the Dynamic Error Spectrum to assess the performance of the trackers with and without probability of visibility incorporated. Simulation results show that the performance of the GNN tracker with visibility concept incorporated is significantly enhanced.

  10. 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…

  11. Segmented Target Design

    NASA Astrophysics Data System (ADS)

    Merhi, Abdul Rahman; Frank, Nathan; Gueye, Paul; Thoennessen, Michael; MoNA Collaboration

    2013-10-01

    A proposed segmented target would improve decay energy measurements of neutron-unbound nuclei. Experiments like this have been performed at the National Superconducting Cyclotron Laboratory (NSCL) located at Michigan State University. Many different nuclei are produced in such experiments, some of which immediately decay into a charged particle and neutron. The charged particles are bent by a large magnet and measured by a suite of charged particle detectors. The neutrons are measured by the Modular Neutron Array (MoNA) and Large Multi-Institutional Scintillation Array (LISA). With the current target setup, a nucleus in a neutron-unbound state is produced with a radioactive beam impinged upon a beryllium target. The resolution of these measurements is very dependent on the target thickness since the nuclear interaction point is unknown. In a segmented target using alternating layers of silicon detectors and Be-targets, the Be-target in which the nuclear reaction takes place would be determined. Thus the experimental resolution would improve. This poster will describe the improvement over the current target along with the status of the design. Work supported by Augustana College and the National Science Foundation grant #0969173.

  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. Targeting novel sites

    PubMed Central

    Shivram, Haridha; Cawley, Dillon

    2011-01-01

    Restriction-like endonuclease (RLE) bearing non-LTR retrotransposons are site-specific elements that integrate into the genome through target primed reverse transcription (TPRT). RLE-bearing elements have been used as a model system for investigating non-LTR retrotransposon integration. R2 elements target a specific site in the 28S rDNA gene. We previously demonstrated that the two major sub-classes of R2 (R2-A and R2-D) target the R2 insertion site in an opposing manner with regard to the pairing of known DNA binding domains and bound sequences—indicating that the A- and D-clades represent independently derived modes of targeting that site. Elements have been discovered that group phylogenetically with R2 but do not target the canonical R2 site. Here we extend our earlier studies to show that a separate R2-A clade element, which targets a site other than the canonical R2 site, does so by using the N-terminal zinc fingers and Myb motifs. We further extend our targeting studies beyond R2 clade elements by investigating the ability of the N-terminal zinc fingers from the nematode NeSL-1 element to target its integration site. Our data are consistent with the use of an N-terminal DNA binding domain as one of the major targeting determinants used by RLE-bearing non-LTR retrotransposons to secure a protein subunit near the insertion site. This N-terminal DNA binding domain can undergo modifications, allowing the element to target novel sites. The binding orientation of the N-terminal domain relative to the insertion site is quite variable. PMID:22479684

  14. Tuberculose pulmonaire révélée par un purpura thrombopénique chez l'enfant-à propos d'un cas clinique observé au service de pédiatrie des Cliniques Universitaires de Lubumbashi

    PubMed Central

    Lubala, Toni Kasole; Mutombo, Augustin Mulangu; Munkana, Arthur Ndundula; Manika, Michel Muteya

    2012-01-01

    Nous rapportons le cas d'un enfant de 7 ans, de sexe masculin ayant présenté un purpura thrombopénique avec épistaxis, hématémèse, otorragies et pétéchies généralisées. Durant la même hospitalisation, nous avons mis en évidence une tuberculose pulmonaire documentée par la présence de bacilles acido-alcoolo résistants à l'examen des crachats. Nous avons observé une majoration du taux de plaquettes en une semaine de corticothérapie intraveineuse à haute dose, avant l'instauration d'une poly chimiothérapie antituberculeuse. Nous rappelons également la controverse que suscite la prise en charge de cette association rarement rapportée. PMID:23077696

  15. 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

  16. Immunogenicity of targeted lentivectors

    PubMed Central

    Goyvaerts, Cleo; Kurt, De Groeve; Lint, Sandra Van; Heirman, Carlo; Van Ginderachter, Jo A.; De Baetselier, Patrick; Raes, Geert; Thielemans, Kris; Breckpot, Karine

    2014-01-01

    To increase the safety and possibly efficacy of HIV-1 derived lentivectors (LVs) as an anti-cancer vaccine, we recently developed the Nanobody (Nb) display technology to target LVs to antigen presenting cells (APCs). In this study, we extend these data with exclusive targeting of LVs to conventional dendritic cells (DCs), which are believed to be the main cross-presenting APCs for the induction of a TH1-conducted antitumor immune response. The immunogenicity of these DC-subtype targeted LVs was compared to that of broad tropism, general APC-targeted and non-infectious LVs. Intranodal immunization with ovalbumin encoding LVs induced proliferation of antigen specific CD4+ T cells, irrespective of the LVs' targeting ability. However, the cytokine secretion profile of the restimulated CD4+ T cells demonstrated that general APC targeting induced a similar TH1-profile as the broad tropism LVs while transduction of conventional DCs alone induced a similar and less potent TH1 profile as the non-infectious LVs. This observation contradicts the hypothesis that conventional DCs are the most important APCs and suggests that the activation of other APCs is also meaningful. Despite these differences, all targeted LVs were able to stimulate cytotoxic T lymphocytes, be it to a lesser extent than broad tropism LVs. Furthermore this induction was shown to be dependent on type I interferon for the targeted and non-infectious LVs, but not for broad tropism LVs. Finally we demonstrated that the APC-targeted LVs were as potent in therapy as broad tropism LVs and as such deliver on their promise as safer and efficacious LV-based vaccines. PMID:24519916

  17. Internal polarized targets

    SciTech Connect

    Kinney, E.R.; Coulter, K.; Gilman, R.; Holt, R.J.; Kowalczyk, R.S.; Napolitano, J.; Potterveld, D.H.; Young, L. ); Mishnev, S.I.; Nikolenko, D.M.; Popov, S.G.; Rachek, I.A.; Temnykh, A.B.; Toporkov, D.K.; Tsentalovich, E.P.; Wojtsekhowski, B.B. . Inst. Yadernoj Fiziki)

    1989-01-01

    Internal polarized targets offer a number of advantages over external targets. After a brief review of the basic motivation and principles behind internal polarized targets, the technical aspects of the atomic storage cell will be discussed in particular. Sources of depolarization and the means by which their effects can be ameliorated will be described, especially depolarization by the intense magnetic fields arising from the circulating particle beam. The experience of the Argonne Novosibirsk collaboration with the use of a storage cell in a 2 GeV electron storage ring will be the focus of this technical discussion. 17 refs., 11 figs.

  18. USGS aerial resolution targets.

    USGS Publications Warehouse

    Salamonowicz, P.H.

    1982-01-01

    It is necessary to measure the achievable resolution of any airborne sensor that is to be used for metric purposes. Laboratory calibration facilities may be inadequate or inappropriate for determining the resolution of non-photographic sensors such as optical-mechanical scanners, television imaging tubes, and linear arrays. However, large target arrays imaged in the field can be used in testing such systems. The USGS has constructed an array of resolution targets in order to permit field testing of a variety of airborne sensing systems. The target array permits any interested organization with an airborne sensing system to accurately determine the operational resolution of its system. -from Author

  19. Molecular Targets Laboratory

    Cancer.gov

    The MTL provides leadership for the translation of basic science advances into drug leads, bioprobes and reagents for molecular target evaluation. exploits chemical and biodiversity repositories, including the NCI Natural Products Repository, for molecula

  20. Molecular Targets Laboratory

    Cancer.gov

    Date Investigator Title  Project Manager(s) December 18, 2000 Philipp Kaldis Cyclin Dependent Kinases as Potential Screening Targets O'Keefe   August 8, 2001 Chem Akin Diana Linnekin Mastocytosis: The Disease, Therapeutic Challenges and Potential Opportun

  1. Molecular Targets Laboratory

    Cancer.gov

    Background Recent advances and insights into the molecular pathogenesis of cancer provide unprecedented opportunities for discovery and development of novel, molecularly targeted diagnostic, therapeutic and preventative strategies and agents. The pivotal

  2. Molecular Targets Laboratory

    Cancer.gov

    Group Mission: Provides chemistry support for bioassay-guided fractionation, isolation, purification and structural characterization of novel, molecularly targeted nonproteinaceous leads from natural products; Reisolates bioactive compounds of interest fo

  3. The SPES Production Target

    NASA Astrophysics Data System (ADS)

    Andrighetto, A.; Biasetto, L.; Manzolaro, M.; Benetti, P.; Cristofolini, I.; di Bernardo, P.; Fontanari, V.; Carturan, M. S.; Cinausero, M.; Colombo, P.; Gramegna, F.; Meneghetti, G.; Monelli, B.; Oboe, R.; Prete, G.; Zanonato, P.

    2009-03-01

    An extended work is in progress concerning the target development for the SPES (Selective Production of Exotic Species) project. The SPES will be an ISOL based facility (Isotope Separation On Line) in which a proton beam of 40 MeV and 0.2 mA impinges directly on a uranium carbide target. After the mass separation and re-acceleration on the experimental sites, the RIBs will have an intensity of the order of 109 pps (for 132Sn) and an energy up to 13 MeV/u. The new idea that characterize this project is the design of its target: we propose a target configuration capable to keep high the number of fissions, low the power deposition and fast the release of the produced isotopes.

  4. Multiple shell fusion targets

    DOEpatents

    Lindl, J.D.; Bangerter, R.O.

    1975-10-31

    Multiple shell fusion targets for use with electron beam and ion beam implosion systems are described. The multiple shell targets are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The targets use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell target can be accomplished.

  5. Molecular Targets Laboratory

    Cancer.gov

    Mission The MTL provides leadership for the translation of basic science advances into drug leads, bioprobes and reagents for molecular target evaluation.  We exploit chemical and biodiversity repositories, including the NCI Natural Products Repository, f

  6. Molecular Targets Laboratory

    Cancer.gov

    The MTL provides an outstanding training environment for qualified predoctoral and postdoctoral individuals interested in furthering their skills and experiences in the multidisciplinary sciences of assay development, target validation, drug discovery res

  7. 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.

  8. Molecular Targets Laboratory

    Cancer.gov

    In addition to the intramural community of world-class scientists comprising the CCR, there are other unique resources available at the NCI that provide extraordinary opportunities for intramural collaborations in molecular target elucidation, validation

  9. T2K Target

    SciTech Connect

    Nakadaira, T.; Haruyama, T.; Kasami, K.; Koike, S.; Ichikawa, A.; Densham, C.; Fitton, M.; Francis, V.; Rooney, M.

    2008-02-21

    We have reported the current development status of the graphite target for J-PARC neutrino beam-line. The conceptual design, the lifetime estimation, the cooling method based of the latest design, and the prototype productions are discussed.

  10. Cutaneous side effects from laser treatment of the skin: skin cancer, scars, wounds, pigmentary changes, and purpura--use of pulsed dye laser, copper vapor laser, and argon laser.

    PubMed

    Haedersdal, M

    1999-01-01

    It has been the intention of this thesis to increase the knowledge on the development of cutaneous side effects from treatment with the argon laser, the copper vapor laser, and the pulsed dye laser, which represent technical developments within laser systems used for treatment of vascular lesions. To reach that goal, the investigations focused on patient and lesional characteristics (skin pigmentation, skin redness, and epidermal thickness) and on the importance of UV irradiation before and after dermatological laser treatment. The aspect of UV irradiation was added because vascular lesions frequently involve the face and, therefore, may be exposed to sunlight in relation to laser treatment. Risk assessments were performed on clinically visible side effects in order to improve the preoperative information to the patients about their individual risks of obtaining side effects from dermatological laser treatment. The laser-induced side effects were evaluated by systematic clinical assessments, by histological and biochemical examinations, by skin reflectance measurements, optical profilometry, and ultrasonography. The term side effects is associated with both transient and permanent skin reactions such as purpura, wounds, textural changes, scars, pigmentary changes, and squamous cell carcinomas. Lightly pigmented, hairless hr/hr C3H/Tif mice, hairless, albino hr/hr MORO/Ibm mice, human, healthy volunteers, and children with port-wine stains were included in the studies. This thesis represents the first systematic and experimental approach to selected side effects from laser treatment of the skin. The argon laser (AL) and the copper vapor laser (CVL) The results from AL and CVL treatments are described together because these lasers are continuous/quasicontinuous lasers that do not meet the requirements for selective photothermolysis, which represents the most selective delivery of energy to cutaneous vessels. In normal-skinned human volunteers, the postoperative development of scars and pigmentary alterations depended on the preoperative constitutive skin pigmentation degree. Significant correlations were found between the preoperative skin pigmentation and the clinically scored pigmentary changes and scarring 1, 2, and 6 months postoperatively, indicating that dark-pigmented skin types respond with more heavy skin reactions than fair-pigmented skin types. Pigmentary changes occurred at lower intensity levels than scarring. No difference was seen between the AL and the CVL concerning the risk of inducing these side effects. In hairless, albino hr/hr MORO/Ibm mice increasing epidermal thicknesses reduced CVL-induced wounds and scars. Significant negative correlations were found between preoperative epidermal thicknesses and CVL-induced skin reactions. In lightly pigmented, hairless hr/hr C3H/Tif mice, CVL treatment induced an increase in skin pigmentation, evaluated by a semiquantitative technique. Postoperative UV irradiations with simulated solar UV increased the CVL-induced skin pigmentation additionally. The size of CVL-induced wounds and scars tended to enlarge by preoperative UV irradiations. In contrast, CVL-induced wounds were diminished and had a prolonged wound healing time when postoperative UV irradiations were given. This may indicate a deep constricted skin damage. Moreover, the histologically evaluated fibrosis and the frequency of bulging infiltration were increased by postoperative UV irradiation. When taking the liberty to extend the obtained results from the animal studies to humans, these results support the importance of pre- and postoperative sunprotection. Regarding skin cancer, in hairless mice it was found that one treatment with the CVL did not have a malignant potential itself. Pretreatment with the CVL at the highest intensity level (1.4W) delayed UV-induced photocarcinogenesis significantly. The pulsed dye laser (PDL) The PDL is described separately because it is the only laser in this thesis that fulf PMID:10605602

  11. Target classification strategies

    NASA Astrophysics Data System (ADS)

    Schachter, Bruce J.

    2015-05-01

    Target classification algorithms have generally kept pace with developments in the academic and commercial sectors since the 1970s. However, most recently, investment into object classification by internet companies and various Human Brain Projects have far outpaced that of the defense sector. Implications are noteworthy. There are some unique characteristics of the military classification problem. Target classification is not solely an algorithm design problem, but is part of a larger system design task. The design flows down from a concept of operations (ConOps) and key performance parameters (KPPs). Inputs are image and/or signal data and time-synchronized metadata. The operation is real-time. The implementation minimizes size, weight and power (SWaP). The output must be conveyed to a time-strapped operator who understands the rules of engagement. It is assumed that the adversary is actively trying to defeat recognition. The target list is often mission dependent, not necessarily a closed set, and may change on a daily basis. It is highly desirable to obtain sufficiently comprehensive training and testing data sets, but costs of doing so are very high and data on certain target types are scarce. The training data may not be representative of battlefield conditions suggesting the avoidance of highly tuned designs. A number of traditional and emerging target classification strategies are reviewed in the context of the military target problem.

  12. Production Target Design Report

    SciTech Connect

    Woloshun, Keith Albert; Dale, Gregory E.; Olivas, Eric Richard

    2015-07-28

    The Northstar 99Mo production target, a cylindrical length of 100Mo rod, has evolved considerably since its first conception.  The cylinder was very early sliced into disks to increase the heat transfer area, first to 1 mm thick disks then to the current 0.5 mm thick.  The coolant was changed early in the target development from water to helium to eliminate corrosion and dissolution.  The diameter has increased from initially 6 mm to 12 mm, the current diameter of the test target now at ANL, to nominally 28 mm (26-30.6 mm, depending upon optimal beam spot size and shape).  The length has also changed to improve the production to cost ratio, so now the target is nominally 41 mm long (excluding coolant gaps between disks), and irradiated on both ends.  This report summarizes the current status of the plant target design.

  13. Targeted multimodal imaging modalities.

    PubMed

    Lee, Seung Yong; Jeon, Seong Ik; Jung, Seulhee; Chung, In Jae; Ahn, Cheol-Hee

    2014-09-30

    Molecular imaging non-invasively visualizes and characterizes the biologic functions and mechanisms in living organisms at a molecular level. In recent years, advances in imaging instruments, imaging probes, assay methods, and quantification techniques have enabled more refined and reliable images for more accurate diagnoses. Multimodal imaging combines two or more imaging modalities into one system to produce details in clinical diagnostic imaging that are more precise than conventional imaging. Multimodal imaging offers complementary advantages: high spatial resolution, soft tissue contrast, and biological information on the molecular level with high sensitivity. However, combining all modalities into a single imaging probe involves problems yet to be solved due to the requirement of high dose contrast agents for a component of imaging modality with low sensitivity. The introduction of targeting moieties into the probes enhances the specific binding of targeted multimodal imaging modalities and selective accumulation of the imaging agents at a disease site to provide more accurate diagnoses. An extensive list of prior reports on the targeted multimodal imaging probes categorized by each modality is presented and discussed. In addition to accurate diagnosis, targeted multimodal imaging agents carrying therapeutic medications make it possible to visualize the theranostic effect and the progress of disease. This will facilitate the development of an imaging-guided therapy, which will widen the application of the targeted multimodal imaging field to experiments in vivo. PMID:25064554

  14. Mitochondria-targeted antioxidants.

    PubMed

    Oyewole, Anne O; Birch-Machin, Mark A

    2015-12-01

    Redox homeostasis is maintained by the antioxidant defense system, which is responsible for eliminating a wide range of oxidants, including reactive oxygen species (ROS), lipid peroxides, and metals. Mitochondria-localized antioxidants are widely studied because the mitochondria, the major producers of intracellular ROS, have been linked to the cause of aging and other chronic diseases. Mitochondria-targeted antioxidants have shown great potential because they cross the mitochondrial phospholipid bilayer and eliminate ROS at the heart of the source. Growing evidence has identified mitochondria-targeted antioxidants, such as MitoQ and tiron, as potentially effective antioxidant therapies against the damage caused by enhanced ROS generation. This literature review summarizes the current knowledge on mitochondria-targeted antioxidants and their contribution to the body's antioxidant defense system. In addition to addressing the concerns surrounding current antioxidant strategies, including difficulties in targeting antioxidant treatment to sites of pathologic oxidative damage, we discuss promising therapeutic agents and new strategic approaches.-Oyewole, A. O., Birch-Machin, M. A. Mitochondria-targeted antioxidants. PMID:26253366

  15. 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.

  16. Targeted assets risk analysis.

    PubMed

    Bouwsema, Barry

    2013-01-01

    Risk assessments utilising the consolidated risk assessment process as described by Public Safety Canada and the Centre for Security Science utilise the five threat categories of natural, human accidental, technological, human intentional and chemical, biological, radiological, nuclear or explosive (CBRNE). The categories of human intentional and CBRNE indicate intended actions against specific targets. It is therefore necessary to be able to identify which pieces of critical infrastructure represent the likely targets of individuals with malicious intent. Using the consolidated risk assessment process and the target capabilities list, coupled with the CARVER methodology and a security vulnerability analysis, it is possible to identify these targeted assets and their weaknesses. This process can help emergency managers to identify where resources should be allocated and funding spent. Targeted Assets Risk Analysis (TARA) presents a new opportunity to improve how risk is measured, monitored, managed and minimised through the four phases of emergency management, namely, prevention, preparation, response and recovery. To reduce risk throughout Canada, Defence Research and Development Canada is interested in researching the potential benefits of a comprehensive approach to risk assessment and management. The TARA provides a framework against which potential human intentional threats can be measured and quantified, thereby improving safety for all Canadians. PMID:23615063

  17. Burglar Target Selection

    PubMed Central

    Townsley, Michael; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

  18. Henoch-Schönlein Purpura

    MedlinePLUS

    ... NIDDK campuses in Maryland and Arizona Research Resources Protocols, repositories, mouse models, plasmids, and more Technology Advancement & ... system response in which the body’s immune system attacks the body’s own cells and organs. Usually, the ...

  19. Phoenix Color Targets

    NASA Technical Reports Server (NTRS)

    2008-01-01

    These images of three Phoenix color targets were taken on sols 1 and 2 by the Surface Stereo Imager (SSI) on board the Phoenix lander. The bottom target was imaged in approximate color (SSI's red, green, and blue filters: 600, 530, and 480 nanometers), while the others were imaged with an infrared filter (750 nanometers). All of them will be imaged many times over the mission to monitor the color calibration of the camera. The two at the top show grains 2 to 3 millimeters in size that were likely lifted to the Phoenix deck during landing. Each of the large color chips on each target contains a strong magnet to protect the interior material from Mars' magnetic dust.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  20. Setting reference targets

    SciTech Connect

    Ruland, R.E.

    1997-04-01

    Reference Targets are used to represent virtual quantities like the magnetic axis of a magnet or the definition of a coordinate system. To explain the function of reference targets in the sequence of the alignment process, this paper will first briefly discuss the geometry of the trajectory design space and of the surveying space, then continue with an overview of a typical alignment process. This is followed by a discussion on magnet fiducialization. While the magnetic measurement methods to determine the magnetic centerline are only listed (they will be discussed in detail in a subsequent talk), emphasis is given to the optical/mechanical methods and to the task of transferring the centerline position to reference targets.

  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. Penetration of concrete targets

    SciTech Connect

    Forrestal, M.J.; Cargile, J.D.; Tzou, R.D.Y.

    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.

  3. Cooled particle accelerator target

    SciTech Connect

    Degtiarenko, Pavel V.

    2005-06-14

    A novel particle beam target comprising: a rotating target disc mounted on a retainer and thermally coupled to a first array of spaced-apart parallel plate fins that extend radially inwardly from the retainer and mesh without physical contact with a second array of spaced-apart parallel plate fins that extend radially outwardly from and are thermally coupled to a cooling mechanism capable of removing heat from said second array of spaced-apart fins and located within the first array of spaced-apart parallel fins. Radiant thermal exchange between the two arrays of parallel plate fins provides removal of heat from the rotating disc. A method of cooling the rotating target is also described.

  4. Targeted polypeptide degradation

    DOEpatents

    Church, George M.; Janse, Daniel M.

    2008-05-13

    This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.

  5. Integrin Targeted Therapeutics

    PubMed Central

    Millard, Melissa; Odde, Srinivas; Neamati, Nouri

    2011-01-01

    Integrins are heterodimeric, transmembrane receptors that function as mechanosensors, adhesion molecules and signal transduction platforms in a multitude of biological processes. As such, integrins are central to the etiology and pathology of many disease states. Therefore, pharmacological inhibition of integrins is of great interest for the treatment and prevention of disease. In the last two decades several integrin-targeted drugs have made their way into clinical use, many others are in clinical trials and still more are showing promise as they advance through preclinical development. Herein, this review examines and evaluates the various drugs and compounds targeting integrins and the disease states in which they are implicated. PMID:21547158

  6. Foam encapsulated targets

    DOEpatents

    Nuckolls, John H. (Livermore, CA); Thiessen, Albert R. (Livermore, CA); Dahlbacka, Glen H. (Livermore, CA)

    1983-01-01

    Foam encapsulated laser-fusion targets wherein a quantity of thermonuclear fuel is embedded in low density, microcellular foam which serves as an electron conduction channel for symmetrical implosion of the fuel by illumination of the target by one or more laser beams. The fuel, such as DT, is contained within a hollow shell constructed of glass, for example, with the foam having a cell size of preferably no greater than 2 .mu.m, a density of 0.065 to 0.6.times.10.sup.3 kg/m.sup.3, and external diameter of less than 200 .mu.m.

  7. Infrared target recognition

    NASA Astrophysics Data System (ADS)

    Singstock, Brian D.

    1991-12-01

    In this thesis, three approaches were used for Automatic Target Recognition (ATR). These approaches were shape, moment and Fourier generated features, Karhunen-Loeve Transform (KLT) generated features and Discrete Cosine Transform (DCT) generated features. The KLT approach was modelled after the face recognition research by Suarez, AFIT, and Turk and Pentland, MIT. A KLT is taken of a reduced covariance matrix, composed all three classes of targets, and the resulting eigenimages are used to reconstruct the original images. The reconstruction coefficients for each original image are found by taking the dot product of the original image with each eigenimage. These reconstruction coefficients were implemented as features into a three layer backprop with momentum network. Using the hold one-cut-out technique of testing data, the net could correctly differentiate the targets 100 percent of the time. Using standard features, the correct classification rate was 99.33 percent. The DCT was also taken of each image, and 16 low frequency Fourier components were kept as features. These recognition rates were compared to FFT results where each set contained the top five feature, as determined by a saliency test. The results proved that the DCT and the FFT were equivalent concerning classification of targets.

  8. Future Fixed Target Facilities

    SciTech Connect

    Melnitchouk, Wolodymyr

    2009-01-01

    We review plans for future fixed target lepton- and hadron-scattering facilities, including the 12 GeV upgraded CEBAF accelerator at Jefferson Lab, neutrino beam facilities at Fermilab, and the antiproton PANDA facility at FAIR. We also briefly review recent theoretical developments which will aid in the interpretation of the data expected from these facilities.

  9. Targeted radionuclide therapy

    PubMed Central

    Williams, Lawrence E.; DeNardo, Gerald L.; Meredith, Ruby F.

    2008-01-01

    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

  10. Spectrally assisted target tracking

    NASA Astrophysics Data System (ADS)

    Hoff, Lawrence E.; Winter, Edwin M.

    2011-09-01

    There has been interest in overhead tracking of automobiles on our roadways using optical sensors. Tracking of multiple vehicles can be accomplished with a single band high-resolution sensor as long as the vehicles are continuously in view. However, in many cases the vehicles pass through or behind blackouts, such as through tunnels or behind tall buildings. In these cases, the vehicles of interest must be reacquired and recognized from the collection of vehicles present after the blackout. The approach considered here is to add an additional sensor to assist a single band high-resolution tracking sensor, where the adjunct sensor measures the vehicle signatures for recognition and reacquisition. The subject of this paper is the recognition of targets of interest amongst the observed objects and the reacquisition after a blackout. A Generalized Likelihood Ratio Test (GLRT) algorithm is compared with the Spectral Angle Mapper (SAM) and Euclidian distance algorithms. All three algorithms were evaluated on a database of signatures created by measuring samples from old automobile gas doors. The GLRT was the most successful in recognizing the target after a blackout and could achieve a 95% correct reacquisition rate. The results show the feasibility of using a hyper spectral sensor to assist a multi target tracking sensor by providing target recognition for reacquisition.

  11. ENFORCEMENT TARGETING 2001

    EPA Science Inventory

    A GIS based targeting methodology which uses multi-media state and federal regulatory data to identify watersheds in Texas, Louisiana, Arkansas, Oklahoma, and New Mexico that are vulnerable to environmental damage and/or have high chemical emissions to the environment. The assess...

  12. 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.

  13. Targeted radionuclide therapy

    SciTech Connect

    Williams, Lawrence E.; DeNardo, Gerald L.; Meredith, Ruby F.

    2008-07-15

    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.

  14. Microenvironmental Targets in Sarcoma

    PubMed Central

    Ehnman, Monika; Larsson, Olle

    2015-01-01

    Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example, in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has led to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject of larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma. PMID:26583076

  15. 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-κB), 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

  16. High purity tungsten targets

    NASA Technical Reports Server (NTRS)

    1975-01-01

    High purity tungsten, which is used for targets in X-ray tubes was considered for space processing. The demand for X-ray tubes was calculated using the growth rates for dental and medical X-ray machines. It is concluded that the cost benefits are uncertain.

  17. Enhanced target factor analysis.

    PubMed

    Rostami, Akram; Abdollahi, Hamid; Maeder, Marcel

    2016-03-10

    Target testing or target factor analysis, TFA, is a well-established soft analysis method. TFA answers the question whether an independent target test vector measured at the same wavelengths as the collection of spectra in a data matrix can be excluded as the spectrum of one of the components in the system under investigation. Essentially, TFA cannot positively prove that a particular test spectrum is the true spectrum of one of the components, it can, only reject a spectrum. However, TFA will not reject, or in other words TFA will accept, many spectra which cannot be component spectra. Enhanced Target Factor Analysis, ETFA addresses the above problem. Compared with traditional TFA, ETFA results in a significantly narrower range of positive results, i.e. the chance of a false positive test result is dramatically reduced. ETFA is based on feasibility testing as described in Refs. [16-19]. The method has been tested and validated with computer generated and real data sets. PMID:26893084

  18. 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.

  19. Targeted adenoviral vectors

    NASA Astrophysics Data System (ADS)

    Douglas, Joanne T.

    The practical implementation of gene therapy in the clinical setting mandates gene delivery vehicles, or vectors, capable of efficient gene delivery selectively to the target disease cells. The utility of adenoviral vectors for gene therapy is restricted by their dependence on the native adenoviral primary cellular receptor for cell entry. Therefore, a number of strategies have been developed to allow CAR-independent infection of specific cell types, including the use of bispecific conjugates and genetic modifications to the adenoviral capsid proteins, in particular the fibre protein. These targeted adenoviral vectors have demonstrated efficient gene transfer in vitro , correlating with a therapeutic benefit in preclinical animal models. Such vectors are predicted to possess enhanced efficacy in human clinical studies, although anatomical barriers to their use must be circumvented.

  20. Mitochondria-targeting particles

    PubMed Central

    Wongrakpanich, Amaraporn; Geary, Sean M; Joiner, Mei-ling A; Anderson, Mark E; Salem, Aliasger K

    2015-01-01

    Mitochondria are a promising therapeutic target for the detection, prevention and treatment of various human diseases such as cancer, neurodegenerative diseases, ischemia-reperfusion injury, diabetes and obesity. To reach mitochondria, therapeutic molecules need to not only gain access to specific organs, but also to overcome multiple barriers such as the cell membrane and the outer and inner mitochondrial membranes. Cellular and mitochondrial barriers can be potentially overcome through the design of mitochondriotropic particulate carriers capable of transporting drug molecules selectively to mitochondria. These particulate carriers or vectors can be made from lipids (liposomes), biodegradable polymers, or metals, protecting the drug cargo from rapid elimination and degradation in vivo. Many formulations can be tailored to target mitochondria by the incorporation of mitochondriotropic agents onto the surface and can be manufactured to desired sizes and molecular charge. Here, we summarize recently reported strategies for delivering therapeutic molecules to mitochondria using various particle-based formulations. PMID:25490424

  1. Cellular Targeting in Autoimmunity

    PubMed Central

    Rogers, Jennifer L.; Serafin, Donald S.; Timoshchenko, Roman G.; Tarrant, Teresa K.

    2012-01-01

    Many biologic agents that were first approved for the treatment of malignancies are now being actively investigated and used in a variety of autoimmune diseases such as rheumatoid arthritis (RA), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, systemic lupus erythematosus (SLE), and Sjogren’s syndrome. The relatively recent advance of selective immune targeting has significantly changed the management of autoimmune disorders, and in part, can be attributed to the progress made in understanding effector cell function and their signaling pathways. In this review, we will discuss the recent FDA approved biologic therapies that directly target immune cells as well as the most promising investigational drugs affecting immune cell function and signaling for the treatment of autoimmune disease. PMID:23054625

  2. Complement-targeted therapeutics

    PubMed Central

    Ricklin, Daniel; Lambris, John D

    2010-01-01

    The complement system is a central component of innate immunity and bridges the innate to the adaptive immune response. However, it can also turn its destructive capabilities against host cells and is involved in numerous diseases and pathological conditions. Modulation of the complement system has been recognized as a promising strategy in drug discovery, and a large number of therapeutic modalities have been developed. However, successful marketing of complement-targeted drugs has proved to be more difficult than initially expected, and many strategies have been discontinued. The US Food and Drug Administration’s approval of the first complement-specific drug, an antibody against complement component C5 (eculizumab; Soliris), in March 2007, was a long-awaited breakthrough in the field. Approval of eculizumab validates the complement system as therapeutic target and might facilitate clinical development of other promising drug candidates. PMID:17989689

  3. Molecular targets in glioblastoma.

    PubMed

    Zorzan, Maira; Giordan, Enrico; Redaelli, Marco; Caretta, Antonio; Mucignat-Caretta, Carla

    2015-01-01

    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

  4. Targeted Therapy for Melanoma.

    PubMed

    Wong, Deborah J L; Ribas, Antoni

    2016-01-01

    Vemurafenib and dabrafenib, two potent tyrosine kinase inhibitors (TKIs) of the BRAF(V600E) kinase, are highly effective in the treatment of a BRAF (V600) -mutant metastatic melanoma. These are selective type I inhibitors (functional against the active conformation of the kinase) of the RAF kinases, which are key players in the mitogen-activated protein kinase (MAPK) pathway. BRAF (V600) mutations are present in approximately 7 % of all cancers, including high frequencies of mutations reported in 50 % of advanced melanomas and 100 % of hairy cell leukemias. As with most targeted therapies, resistance to BRAF inhibitors is an issue, and mechanisms of resistance are varied. Combining BRAF inhibitors with MEK inhibitors such as trametinib delays the development of resistance. Rationally combining targeted therapies to address the mechanism of resistance or combining BRAF inhibitors with other effective therapies such as immunotherapy may result in further improvement in outcomes for patients. PMID:26601866

  5. Targeted cancer immunotherapy.

    PubMed

    Zigler, Maya; Shir, Alexei; Levitzki, Alexander

    2013-08-01

    The understanding that the immune system plays a dual role in cancer progression has led to the recent development of targeted immunotherapies. These treatments, which aim to harness the immune system against cancer, include monoclonal antibodies, immune adjuvants, cell-based therapy and vaccines. Although numerous immune-targeted treatment modalities have entered the clinic, most have shown limited efficacy. The intrinsic heterogeneity and genomic instability of the tumor, coupled with immune suppression induced by both the tumor and its microenvironment, remain the main obstacles to the success of these therapies. We believe that the primary objective of the new generation of therapies must be to reinstate immune surveillance against primary and metastatic tumor cells, while inhibiting the immune suppressive microenvironment. Most probably this will be achieved by combining several treatment modalities. This paper will briefly review current immunotherapies and their promise, as well as the obstacles associated with them. PMID:23648271

  6. Cellular targeting in autoimmunity.

    PubMed

    Rogers, Jennifer L; Serafin, Donald S; Timoshchenko, Roman G; Tarrant, Teresa K

    2012-12-01

    Many biologic agents that were first approved for the treatment of malignancies are now being actively investigated and used in a variety of autoimmune diseases such as rheumatoid arthritis (RA), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, systemic lupus erythematosus (SLE), and Sjogren's syndrome. The relatively recent advance of selective immune targeting has significantly changed the management of autoimmune disorders and in part can be attributed to the progress made in understanding effector cell function and their signaling pathways. In this review, we will discuss the recent FDA-approved biologic therapies that directly target immune cells as well as the most promising investigational drugs affecting immune cell function and signaling for the treatment of autoimmune disease. PMID:23054625

  7. Targeting biodefense markets.

    PubMed

    Olinger, Gene Garrard

    2009-10-01

    The "World Vaccine Congress 2009" held in Washington D.C. (April 20-23, 2009) sponsored several sessions focused on the vaccine market targeting biodefense. On day one of the congress, a panel discussion outlined the federal progress in medical countermeasure preparedness that included emerging infections, influenza, and biodefense focuses. The second day, a session focused on the biodefense vaccine market with both government and industry members discussing the opportunities and challenges associated with the budding market. PMID:19855169

  8. Targeted chiral lipidomics analysis.

    PubMed

    Lee, Seon Hwa; Williams, Michelle V; Blair, Ian A

    2005-09-01

    Genomics, transcriptomics, and proteomics are proving to be very useful techniques, which have impacted significantly on our understanding mechanisms of human disease. However, this systems biology approach has several drawbacks than can be overcome by the integration of metabonomics and lipidomics. We have developed a targeted lipidomics approach that makes it possible to directly analyze chiral lipids generated in cellular systems. Bioactive lipids are usually present in trace amounts as enanatiomers and regioisomers that require separation before they can be analyzed by mass spectrometry. Normal phase chiral chromatography is generally used to resolve bioactive lipid enanatiomers. However, conventional electrospray and atmospheric pressure chemical ionization/tandem mass spectrometry have limited sensitivity when normal phase solvents are used, which makes it difficult to conduct studies when only trace amounts of the bioactive lipids are present. The use of electron capture atmospheric pressure chemical ionization/tandem mass spectrometry overcomes this problem. Enantiomers and regioisomers of targeted bioactive lipids can be quantified using stable isotope dilution methodology coupled with normal phase chiral chromatography and electron capture atmospheric chemical ionization/tandem mass spectrometry. A targeted lipidomics profile from rat epithelial cells transfected with cyclooxygenase-2 and maintained in culture was obtained. Inhibition with the non-selective cyclooxygenase inhibitor aspirin increased the formation of 15(R)-hydroxyeicosatetraenoic acid in the cells although it completely inhibited formation of the 15(S)-enantiomer and prostaglandin E2. New mass spectrometry instrumentation with an improved atmospheric pressure chemical ionization source was found to be an order of magnitude more sensitive than existing instruments for analysis of bioactive lipids using electron capture methodology. This type of mass spectrometer will permit a more detailed analysis of cellular bioactive lipid production than has been possible previously. It will also permit in vivo targeted lipidomics studies to be conducted using biological fluids derived from animal models and human subjects. PMID:16099399

  9. New targets for DBS.

    PubMed

    Benabid, Alim Louis; Torres, Napoleon

    2012-01-01

    The specific effect of DBS at high frequency, discovered during a VIM thalamotomy, was extended to the older targets of ablative neurosurgery such as the pallidum, for tremor in Parkinson's disease (PD), dyskinesias, essential tremor, as well as the internal capsule to treat psychiatric disorders (OCD). A second wave of targets came from basic research, enabled by the low morbidity, reversibility, and adaptability of DBS. This was the case for the subthalamic nucleus (STN) which improves the triad of dopaminergic symptoms, and the pedunculopontine nucleus (PPN) for gait disorders in PD. The new concepts of the role of basal ganglia in psychiatric disorders indicate the subgenual cortex CG 25 for severe resistant depression, the accumbens nucleus for depression, anorexia nervosa, and addiction, and the thalamus intralaminar nuclei for minimally conscious states. Serendipity and a scientific approach have provided several instances where targets have produced unexpected effects (such as STN in OCD), as well as limbic effects observed during attempts at VMH stimulation for obesity: this might offer a novel way to treat mild cognitive impairment, or memory deficits reported in Alzheimer's disease. While these might provide solutions for as yet unsolved problems, attention must be paid to ethical considerations. PMID:22166437

  10. Targeted endoscopic imaging.

    PubMed

    Li, Meng; Wang, Thomas D

    2009-04-01

    Endoscopy has undergone explosive technological growth in recent years, and with the emergence of targeted imaging, its truly transformative power and impact on 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 anatomic 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 could 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 US Food and Drug Administration 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

  11. Nanocrystal targeting in vivo

    NASA Astrophysics Data System (ADS)

    Åkerman, Maria E.; Chan, Warren C. W.; Laakkonen, Pirjo; Bhatia, Sangeeta N.; Ruoslahti, Erkki

    2002-10-01

    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 known as the reticuloendothelial system. We set out to explore the feasibility of in vivo targeting by using semiconductor quantum dots (qdots). Qdots are small (<10 nm) inorganic nanocrystals that possess unique luminescent properties; their fluorescence emission is stable and tuned by varying the particle size or composition. We show that ZnS-capped CdSe qdots coated with a lung-targeting peptide accumulate in the lungs of mice after i.v. injection, whereas two other peptides specifically direct qdots to blood vessels or lymphatic vessels in tumors. We also show that adding polyethylene glycol to the qdot coating prevents nonselective accumulation of qdots in reticuloendothelial tissues. These results encourage the construction of more complex nanostructures with capabilities such as disease sensing and drug delivery.

  12. Targeting Inactive Enzyme Conformation

    PubMed Central

    Liu, Sijiu; Zeng, Li-Fan; Wu, Li; Yu, Xiao; Xue, Ting; Gunawan, Andrea M.; Ya-Qiu, Long; Zhang, Zhong-Yin

    2009-01-01

    There has been considerable interest in protein tyrosine phosphatase 1B (PTP1B) as a therapeutic target for diabetes, obesity, as well as cancer. Identifying inhibitory compounds with good bioavailability is a major challenge of drug discovery programs targeted toward PTPs. Most current PTP active site-directed pharmacophores are negatively charged pTyr mimetics which cannot readily enter the cell. This lack of cell permeability limits the utility of such compounds in signaling studies and further therapeutic development. We identify aryl diketoacids as novel pTyr surrogates and show that neutral amide-linked aryl diketoacid dimers also exhibit excellent PTP inhibitory activity. Kinetic studies establish that these aryl diketoacid derivatives act as noncompetitive inhibitors of PTP1B. Crystal structures of ligand-bound PTP1B reveal that both the aryl diketoacid and its dimeric derivative bind PTP1B at the active site, albeit with distinct modes of interaction, in the catalytically inactive, WPD loop open conformation. Furthermore, dimeric aryl diketoacids are cell permeable and enhance insulin signaling in hepatoma cells, suggesting that targeting the inactive conformation may provide a unique opportunity for creating active site-directed PTP1B inhibitors with improved pharmacological properties. PMID:19012396

  13. Gene targeting in Arabidopsis.

    PubMed

    Hanin, M; Volrath, S; Bogucki, A; Briker, M; Ward, E; Paszkowski, J

    2001-12-01

    Precise modification by gene targeting (GT) provides an important tool for studies of gene function in vivo. Although routine with many organisms, only isolated examples of GT events have been reported for flowering plants. These were at low frequencies precluding reliable estimation of targeting efficiency and evaluation of GT mechanisms. Here we present an unambiguous and straightforward system for detection of GT events in Arabidopsis using an endogenous nuclear gene encoding protoporphyrinogen oxidase (PPO), involved in chlorophyll and heme syntheses. Inhibition of PPO by the herbicide Butafenacil results in rapid plant death. However, the combination of two particular mutations renders PPO highly resistant to Butafenacil. We exploited this feature for selection of GT events by introducing the mutations into the PPO gene by homologous recombination. We have estimated the basal GT frequency to be 2.4 x 10(-3). Approximately one-third of events were true GT (TGT) leading to the anticipated modification of the chromosomal PPO copy. The remaining events could be classified as ectopic GT (EGT) arising by modification of vector DNA by the chromosomal template and its random integration into the Arabidopsis genome. Thus the TGT frequency in our experimental setup is 0.72 x 10(-3). In view of the high efficiency of Arabidopsis transformation, GT experiments of a reasonable size followed by a PCR screen for GT events should also allow for modification of non-selectable targets. Moreover, the system presented here should contribute significantly to future improvement of GT technology in plants. PMID:11851913

  14. Bromodomains as therapeutic targets

    PubMed Central

    Muller, Susanne; Filippakopoulos, Panagis; Knapp, Stefan

    2011-01-01

    Acetylation of lysine residues is a post-translational modification with broad relevance to cellular signalling and disease biology. Enzymes that ‘write’ (histone acetyltransferases, HATs) and ‘erase’ (histone deacetylases, HDACs) acetylation sites are an area of extensive research in current drug development, but very few potent inhibitors that modulate the ‘reading process’ mediated by acetyl lysines have been described. The principal readers of ?-N-acetyl lysine (Kac) marks are bromodomains (BRDs), which are a diverse family of evolutionary conserved protein-interaction modules. The conserved BRD fold contains a deep, largely hydrophobic acetyl lysine binding site, which represents an attractive pocket for the development of small, pharmaceutically active molecules. Proteins that contain BRDs have been implicated in the development of a large variety of diseases. Recently, two highly potent and selective inhibitors that target BRDs of the BET (bromodomains and extra-terminal) family provided compelling data supporting targeting of these BRDs in inflammation and in an aggressive type of squamous cell carcinoma. It is likely that BRDs will emerge alongside HATs and HDACs as interesting targets for drug development for the large number of diseases that are caused by aberrant acetylation of lysine residues. PMID:21933453

  15. 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

  16. 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.

  17. 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

  18. Genetic targeting of microglia.

    PubMed

    Wieghofer, Peter; Knobeloch, Klaus-Peter; Prinz, Marco

    2015-01-01

    Genetic targeting of microglia and other myeloid cells in the central nervous system (CNS) is highly desirable as they are critical effectors and regulators of changes in CNS homeostasis during development as well as in health and disease. Therefore, genetic reprogramming of microglia could constitute a central approach for potentially reducing disease burden. Previous attempts to target only microglia in vivo failed because of the similarities to their hematopoietic relatives in the circulation. However, this concept has been challenged by recent results of developmental and gene expression profiling studies which used novel molecular biological tools to unravel the origin of microglia and to define their role as specialized tissue macrophages clearly distinct from monocytes or monocyte-derived macrophages. The aim of this review is to recapitulate the history of microglia targeting approaches and finally highlight recent achievements in the field. We will discuss the pros and cons of the newly available genetic tools, their potential for future microglia research and genetic strategies. PMID:25132502

  19. CDTI target selection criteria

    NASA Technical Reports Server (NTRS)

    Britt, C. L.; Davis, C. M.; Jackson, C. B.; Mcclellan, V. A.

    1984-01-01

    A Cockpit Display of Traffic Information (CDTI) is a cockpit instrument which provides information to the aircrew on the relative location of aircraft traffic in the vicinity of their aircraft (township). In addition, the CDTI may provide information to assist in navigation and in aircraft control. It is usually anticipated that the CDTI will be integrated with a horizontal situation indicator used for navigational purposes and/or with a weather radar display. In this study, several sets of aircraft traffic data are analyzed to determine statistics on the number of targets that will be displayed on a CDTI using various target selection criteria. Traffic data were obtained from an Atlanta Terminal Area Simulation and from radar tapes recorded at the Atlanta and Miami terminal areas. Results are given in the form of plots showing the average percentage of time (or probability) that an aircraft equipped with a CDTI would observe from 0 to 10 other aircraft on the display for range settings on the CDTI up to 30 n. mi. and using various target discrimination techniques.

  20. 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

  1. Marasmius oreades lectin induces renal thrombotic microangiopathic lesions.

    PubMed

    Warner, Roscoe L; Winter, Harry C; Speyer, Cecilia L; Varani, James; Oldstein, Irwin J; Murphy, Hedwig S; Johnson, Kent J

    2004-10-01

    The present studies demonstrate that infusion of a type B specific lectin derived from the mushroom Marasmius oreades (MOA) into mice binds selectively to the glomerular endothelial cells via surface carbohydrate moieties resulting in cell injury and death associated with platelet-fibrin thrombi. This selective MOA binding to the endothelial cells can be abrogated by a sugar specific for the carbohydrate sequence. Hemolytic-Uremic Syndrome (HUS) and the closely associated Thrombotic Thrombocytopenic Purpura (TTP) are diseases associated with widespread microvascular injury in various organs. Clinically, these diseases are associated with microangiopathic hemolytic anemia and thrombocytopenia. The kidney glomerulus is a primary target of this microvascular injury. There are many underlying etiologies including bacterial toxins. Experimentally, such toxins injure endothelial cells in vitro but in vivo studies have failed to reproduce the characteristic renal pathology. We suggest that MOA-induced glomerular microangiopathic injury could be used to study the pathophysiology of endothelial cell injury as related to glomerular microangiopathic injury. PMID:15351229

  2. Keeping von Willebrand Factor under Control: Alternatives for ADAMTS13.

    PubMed

    Tersteeg, Claudia; Fijnheer, Rob; Pasterkamp, Gerard; de Groot, Philip G; Vanhoorelbeke, Karen; de Maat, Steven; Maas, Coen

    2016-02-01

    Von Willebrand factor (VWF) is one of the most important proteins of the hemostatic system. Its multimeric state is essential for its natural function to guide platelets to sites of injury. ADAMTS13 is the key protease that regulates the multimeric state of VWF. Without ADAMTS13, VWF multimers can grow to pathologically large sizes. This is a risk factor for the life-threatening condition thrombotic thrombocytopenic purpura (TTP). In this condition, VWF-rich thrombi occlude the microvasculature of various tissues. Intriguingly, a complete ADAMTS13 deficiency does not cause continuous TTP, either in patients or genetically targeted mice. Instead, TTP occurs in episodes of disease, separated by extended periods of remission. This indicates that regulating factors beyond ADAMTS13 are likely involved in this pathologic cascade of events. This raises the question of what really happens when ADAMTS13 is (temporarily) unavailable. In this review, we explore the possible role of complementary mechanisms that are capable of modifying the thrombogenic potential of VWF. PMID:26595154

  3. 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 α 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 (ΔΨm) 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

  4. Clinical Application of Partial Splenic Embolization

    PubMed Central

    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

  5. Internal targets at storage rings

    NASA Astrophysics Data System (ADS)

    Grigoryev, Kirill

    2015-11-01

    Internal targets play an important role in nuclear and high energy physics research. After many decades of development, these targets have become very common and highly complex devices. Different types of polarized and unpolarized targets, such as atomic beam, gaseous-, liquid- and solid-state targets, are used in various experiments at storage rings all over the world. The choice and usage of devices (both current and those in development) for internal experiments are strongly dependent on the many parameters of stored beams (e.g. dimensions, lifetime, cooling availability and polarization) and design parameters of the target (areal density, dimensions of the interaction point, target cooling, the gas load to the target chamber and time structure of the target). All these parameters are tightly coupled and must be considered together. The different internal targets are presented in this paper.

  6. Right on Target

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This map shows the estimated location of the Mars Exploration Rover Spirit within Gusev Crater, Mars. Engineers targeted Spirit for the center of the blue ellipse. Measurements taken during the rover's descent by the Deep Space Network predicted its landing site to be the spot marked with a black dot. Later measurements taken on the ground by both the Deep Space Network and the orbiter Mars Odyssey narrowed the predicted landing site to a spot marked with a white dot. When initially choosing a landing site for the rover, engineers avoided hazardous terrain outlined here in yellow and red. This map consists of data from Mars Odyssey and Mars Global Surveyor.

  7. Targeting Breast Cancer Metastasis

    PubMed Central

    Jin, Xin; Mu, Ping

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting. PMID:26380552

  8. EGFR-targeted therapy.

    PubMed

    Vecchione, Loredana; Jacobs, Bart; Normanno, Nicola; Ciardiello, Fortunato; Tejpar, Sabine

    2011-11-15

    Anti-Epidermal Growth Factor Receptor (EGFR) therapies have been recently developed for the treatment of multiple cancer types. At the time when they were introduced in clinical practice, there was little knowledge of the molecular bases of tumor sensitivity and resistance to these novel targeted compounds. By using the framework of anti-EGFR inhibitors as treatment for colorectal cancer patients, we will review the knowledge we have reached until now in improving the development of a personalized cancer therapy and we will try to indicate the future challenges this field will face in the future. PMID:21925171

  9. Target mass corrections revisited

    SciTech Connect

    Steffens, F.M.; Melnitchouk, W.

    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}.

  10. 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}.

  11. Pharmacologic agents targeting autophagy

    PubMed Central

    Vakifahmetoglu-Norberg, Helin; Xia, Hong-guang; Yuan, Junying

    2015-01-01

    Autophagy is an important intracellular catabolic mechanism critically involved in regulating tissue homeostasis. The implication of autophagy in human diseases and the need to understand its regulatory mechanisms in mammalian cells have stimulated research efforts that led to the development of high-throughput screening protocols and small-molecule modulators that can activate or inhibit autophagy. Herein we review the current landscape in the development of screening technology as well as the molecules and pharmacologic agents targeting the regulatory mechanisms of autophagy. We also evaluate the potential therapeutic application of these compounds in different human pathologies. PMID:25654545

  12. Non-Targeted Analysis Challenge (Non-targeted screening workshop)

    EPA Science Inventory

    This brief presentation is intended to motivate discussion of the "Non-Targeted Analysis Challenge" at the Advancing Non-Targeted Analyses of Xenobiotics in Environmental and Biological Media workshop held at the EPA RTP campus.

  13. Targeting adipose tissue

    PubMed Central

    2012-01-01

    Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT) is generally known and stores excess energy in the form of triacylglycerol (TG), insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT) helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP). The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET), however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs), activators of peroxisome proliferator-activated receptor γ (PPARγ) a ‘master’ regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity. PMID:23102228

  14. Gene targeting in plants

    PubMed Central

    Paszkowski, Jerzy; Baur, Markus; Bogucki, Augustyn; Potrykus, Ingo

    1988-01-01

    Although the generation of transgenic plants is now routine, the integration of foreign genetic information has so far been at random sites in the genome. We now present evidence for directed integration into a predicted location in the host plant genome. Protoplasts of transgenic tobacco (Nicotiana tabaccum) plants carrying copies of a partial, non-functional drug-resistance gene in the nuclear DNA were used as recipients for DNA molecules containing the missing part of the gene. Molecular and genetic data confirm the integration of the foreign DNA through homologous recombination within overlapping parts of the protein coding region, resulting in the formation of an active gene in the host chromosome. This approach is referred to as gene targeting. The gene targeting frequency (the number of drug-resistant clones resulting from gene correction compared to the number of resistant clones from parallel experiments with a similar non-interrupted hybrid gene) was 0.5-4.2×10-4. These experiments demonstrate the possibility of producing transgenic plants with desired modifications to a specific nuclear gene. Images PMID:16453864

  15. 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.

  16. 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

  17. Liquid Hydrogen: Target, Detector

    SciTech Connect

    Mulholland, G.T.; Harigel, G.G.

    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.

  18. Rotating Target Development for SNS Second Target Station

    SciTech Connect

    McManamy, Thomas J; Rennich, Mark J; Crawford, Roy K; Geoghegan, Patrick J; Janney, Jim G

    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

  19. 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.

  20. Target detection portal

    SciTech Connect

    Linker, Kevin L.; Brusseau, Charles A.

    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.

  1. Electromagnetic targeting of guns

    SciTech Connect

    Pogue, E.W.; Boat, R.M.; Holden, D.N.; Lopez, J.R.

    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.

  2. 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.; 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.

  3. 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

  4. Stroke Neuroprotection: Targeting Mitochondria

    PubMed Central

    Talley Watts, Lora; Lloyd, Reginald; Justin Garling, Richard; Duong, Timothy

    2013-01-01

    Stroke is the fourth leading cause of death and the leading cause of long-term disability in the United States. Blood flow deficit results in an expanding infarct core with a time-sensitive peri-infarct penumbra that is considered salvageable and is the primary target for treatment strategies. The only current FDA-approved drug for treating ischemic stroke is recombinant tissue plasminogen activator (rt-PA). However, this treatment is limited to within 4.5 h of stroke onset in a small subset of patients. The goal of this review is to focus on mitochondrial-dependent therapeutic agents that could provide neuroprotection following stroke. Dysfunctional mitochondria are linked to neurodegeneration in many disease processes including stroke. The mechanisms reviewed include: (1) increasing ATP production by purinergic receptor stimulation, (2) decreasing the production of ROS by superoxide dismutase, or (3) increasing antioxidant defenses by methylene blue, and their benefits in providing neuroprotection following a stroke. PMID:24961414

  5. Design of ligand-targeted nanoparticles for enhanced cancer targeting

    NASA Astrophysics Data System (ADS)

    Stefanick, Jared F.

    Ligand-targeted nanoparticles are increasingly used as drug delivery vehicles for cancer therapy, yet have not consistently produced successful clinical outcomes. Although these inconsistencies may arise from differences in disease models and target receptors, nanoparticle design parameters can significantly influence therapeutic efficacy. By employing a multifaceted synthetic strategy to prepare peptide-targeted nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities, this work evaluates the roles of polyethylene glycol (PEG) coating, ethylene glycol (EG) peptide-linker length, peptide hydrophilicity, peptide density, and nanoparticle size on tumor targeting in a systematic manner. These parameters were analyzed in multiple disease models by targeting human epidermal growth factor receptor 2 (HER2) in breast cancer and very late antigen-4 (VLA-4) in multiple myeloma to demonstrate the widespread applicability of this approach. By increasing the hydrophilicity of the targeting peptide sequence and simultaneously optimizing the EG peptide-linker length, the in vitro cellular uptake of targeted liposomes was significantly enhanced. Specifically, including a short oligolysine chain adjacent to the targeting peptide sequence effectively increased cellular uptake ~80-fold using an EG6 peptide-linker compared to ~10-fold using an EG45 linker. In vivo, targeted liposomes prepared in a traditional manner lacking the oligolysine chain demonstrated similar biodistribution and tumor uptake to non-targeted liposomes. However, by including the oligolysine chain, targeted liposomes using an EG45 linker significantly improved tumor uptake ~8-fold over non-targeted liposomes, while the use of an EG6 linker decreased tumor accumulation and uptake, owing to differences in cellular uptake kinetics, clearance mechanisms, and binding site barrier effects. To further improve tumor targeting and enhance the selectivity of targeted nanoparticles, a dual-receptor targeted approach was evaluated by targeting multiple cell surface receptors simultaneously. Liposomes functionalized with two distinct peptide antagonists to target VLA-4 and Leukocyte Peyer's Patch Adhesion Molecule-1 (LPAM-1) demonstrated synergistically enhanced cellular uptake by cells overexpressing both target receptors and negligible uptake by cells that do not simultaneously express both receptors, providing a strategy to improve selectivity over conventional single receptor-targeted designs. Taken together, this process of systematic optimization of well-defined nanoparticle drug delivery systems has the potential to improve cancer therapy for a broader patient population.

  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. Mobile target ladar ATR system

    NASA Astrophysics Data System (ADS)

    Hodge, Jesse L.; DeKruger, David H.; Park, Alden E.

    2001-10-01

    The Mobile Target Acquisition System (MTAS) is an automatic target recognition (ATR) system developed by the Naval Air Warfare Center Weapons Division, China Lake, CA, under funding by the Office of Naval Research (ONR) to detect and identify mobile target laser detection and ranging (LADAR) range signatures. The primary objective was to achieve high correct system identification rates for range signatures of relatively low numbers of pixels on target and, at the same time, maintain a low system identification false alarm rate. MTAS met this objective by stressing conservation and efficient exploitation of target information at all levels of processing. Adaptive noise cleaning conserves target information by filtering pixels only when the pixel and its neighbors satisfied the criteria for range dropouts. The MTAS detector holds false alarms to a low level by convolving synthetic templates with the gradient of the range image and fusing the resulting correlation surface with a blob size filter. Mobile target identification fuses 2-D silhouette shape with 3-D (21/2-D) volumetric shape where the mixture of 2- and 3-D shapes is controlled by a single parameter. The match between the measured LADAR range signature and the synthetic range template efficiently and effectively exploits scarce target information by including all target and template pixels in the Fuzzy Tanimoto Distance similarity measure. This system has successfully detected and identified measured mobile LADAR target signatures with 200 pixels on target and greater with a low confuser identification rate and no system clutter identification false alarms.

  8. Target control of complex networks.

    PubMed

    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

  9. Using the Nova target chamber for high-yield targets

    SciTech Connect

    Pitts, J.H.

    1987-09-28

    The existing 2.2-m-radius Nova aluminum target chamber, coated and lined with boron-seeded carbon shields, is proposed for use with 1000-MJ-yield targets in the next laser facility. The laser beam and diagnostic holes in the target chamber are left open and the desired 10/sup -2/ Torr vacuum is maintained both inside and outside the target chamber; a larger target chamber room is the vacuum barrier to the atmosphere. The hole area available is three times that necessary to maintain a maximum fluence below 12 J/cm/sup 2/ on optics placed at a radius of 10 m. Maximum stress in the target chamber wall is 73 MPa, which complies with the intent of the ASME Pressure Vessel Code. However, shock waves passing through the inner carbon shield could cause it to comminute. We propose tests and analyses to ensure that the inner carbon shield survives the environment. 13 refs.

  10. Targeting tumor acidity

    NASA Astrophysics Data System (ADS)

    Reshetnyak, Yana K.; Engelman, Donald M.; Andreev, Oleg A.

    2012-02-01

    One of the main features of solid tumors is extracellular acidity, which correlates with tumor aggressiveness and metastatic potential. We introduced novel approach in targeting of acidic tumors, and translocation of cell-impermeable cargo molecules across cellular membrane. Our approach is based on main principle of insertion and folding of a polypeptide in lipid bilayer of membrane. We have identified family of pH Low Insertion Peptides (pHLIPs), which are capable spontaneous insertion and folding in membrane at mild acidic conditions. The affinity of peptides of pHLIP family to membrane at low pH is several times higher than at neutral pH. The process of peptides folding occurs within milliseconds. The energy released in a result of folding (about 2 kcal/mol) could be used to move polar cargo across a membrane, which is a novel concept in drug delivery. pHLIP peptides could be considered as a pH-sensitive single peptide molecular transporters and conjugated with imaging probes for fluorescence, MR, PET and SPECT imaging, they represent a novel in vivo marker of acidity. The work is supported by NIH grants CA133890 and GM073857 to OAA, DME, YRK.

  11. Epigenomes as therapeutic targets.

    PubMed

    Hamm, Christopher A; Costa, Fabricio F

    2015-07-01

    Epigenetics is a molecular phenomenon that pertains to heritable changes in gene expression that do not involve changes in the DNA sequence. Epigenetic modifications in a whole genome, known as the epigenome, play an essential role in the regulation of gene expression in both normal development and disease. Traditional epigenetic changes include DNA methylation and histone modifications. Recent evidence reveals that other players, such as non-coding RNAs, may have an epigenetic regulatory role. Aberrant epigenetic signaling is becoming to be known as a central component of human disease, and the reversible nature of the epigenetic modifications provides an exciting opportunity for the development of clinically relevant therapeutics. Current epigenetic therapies provide a clinical benefit through disrupting DNA methyltransferases or histone deacetylases. However, the emergence of next-generation epigenetic therapies provides an opportunity to more effectively disrupt epigenetic disease states. Novel epigenetic therapies may improve drug targeting and drug delivery, optimize dosing schedules, and improve the efficacy of preexisting treatment modalities (chemotherapy, radiation, and immunotherapy). This review discusses the epigenetic mechanisms that contribute to the disease, available epigenetic therapies, epigenetic therapies currently in development, and the potential future use of epigenetic therapeutics in a clinical setting. PMID:25797698

  12. 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

  13. Facility target insert shielding assessment

    SciTech Connect

    Mocko, Michal

    2015-10-06

    Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In the present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.

  14. 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.

  15. 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).

  16. 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.

  17. 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.

  18. Targeted Nanotechnology for Cancer Imaging

    PubMed Central

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

    2014-01-01

    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

  19. Target engagement in lead generation.

    PubMed

    Durham, Timothy B; Blanco, Maria-Jesus

    2015-03-01

    The pharmaceutical industry is currently facing multiple challenges, in particular the low number of new drug approvals in spite of the high level of R&D investment. In order to improve target selection and assess properly the clinical hypothesis, it is important to start building an integrated drug discovery approach during Lead Generation. This should include special emphasis on evaluating target engagement in the target tissue and linking preclinical to clinical readouts. In this review, we would like to illustrate several strategies and technologies for assessing target engagement and the value of its application to medicinal chemistry efforts. PMID:25630223

  20. Summary of Recent Target Studies

    SciTech Connect

    Bieniosek, F.; O'Day, S.

    1993-02-04

    This report describes recent measurements that have been performed with the new target stack (Fig. 1). Highlights of these measurements are: (1) Pbar yields of nickel and powdered rhenium are comparable to that of copper. (2) Enhancement of pbar yield at the interface between copper and aluminum disks in the target stack has been observed. This effect occurs only when the lens is focused near the upstream edge of the target. (3) The target density depletion study in powdered rhenium showed an apparent yield reduction on the time scale of a single proton pulse, accompanied by release of airborne radioactive material.

  1. A high yield neutron target

    NASA Technical Reports Server (NTRS)

    Alger, D. L.; Steinberg, R.; Weisenbach, P.

    1974-01-01

    Target, in cylinder form, rotates rapidly in front of beam. Titanium tritide film is much thicker than range of accelerated deutron. Sputtering electrode permits full use of thick film. Stream of high-velocity coolant provides efficient transfer of heat from target.

  2. Temporal Yoking in Target Detection.

    PubMed

    Potter, Mary; Hagmann, Carl; Wan, Quan

    2015-09-01

    Temporal yoking has been shown to enhance performance in dual auditory-visual tasks (Jiang & Swallow, 2014). Here we investigate the relative timing of a picture target in an RSVP sequence and the spoken name of the target. Prior studies (Potter, Wyble, Hagmann, & McCourt, 2014) showed that presenting a written target name 900 ms before the visual sequence led to more accurate detection than when the name appeared 200 ms after the sequence. By using a spoken target name in the present study, we avoided visual interference between the name and the visual sequence, enabling us to investigate temporal yoking in greater detail. The target, which appeared on 50% of the trials, was one of a stream of 6 pictures presented for 53 ms per picture; all pictures were new to the participants. The spoken name of the target began at four possible times, relative to the onset of the 320 ms picture sequence: 1000 or 500 ms before the sequence, at the beginning, or 500 ms after the beginning of the sequence (180 ms after the sequence ended). Strikingly, performance remained well above chance in each temporal condition, although it dropped significantly the later the onset of the spoken target. While advance conceptual information can enhance picture selection, matching can still occur when the target information is simultaneous with or immediately follows the sequence. Meeting abstract presented at VSS 2015. PMID:26326044

  3. The Kepler Dropped Target Program

    NASA Astrophysics Data System (ADS)

    Haas, Michael Robert; Dotson, J. L.; Batalha, N.; Gilliland, R. L.; Walkowicz, L.; Gautier, T. N.; Cochran, W. D.

    2010-01-01

    Kepler provides high-precision optical photometry of over 160000 stars on a 30-min cadence and 512 stars on a 1-min cadence. During the nominal 3.5-year mission, the target list will be updated at regular intervals to eliminate misclassified giants and highly variable stars and, late in the mission, the target list will be trimmed to accommodate decreased bandwidth. The data from these dropped targets will provide a unique and valuable legacy for stellar astrophysics. After commissioning and one-month of science data collection, Kepler has already dropped more than 8400 targets and posted the available data to the Multi-mission Archive at STScI (MAST). This treasure of dropped targets will continue to grow over the life of the mission. Since this data becomes public 60 days after the targets are officially dropped, it provides a unique opportunity for early community involvement. This presentation describes how the data can be accessed to exploit this legacy and provides some examples of dropped target light curves. Dropped targets of particular interest can be proposed for further observation through Kepler's Guest Observer Program on an annual basis. Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA, Science Mission Directorate.

  4. 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

  5. Type of Cancer Treatment: Targeted Therapy

    Cancer.gov

    Information about the role that targeted therapies play in cancer treatment. Includes how targeted therapies work against cancer, who receives targeted therapies, common side effects, and what to expect when having targeted therapies.

  6. Target tracking using area correlation

    NASA Astrophysics Data System (ADS)

    Jackson, R. M. B.

    1980-11-01

    The tracking system described based on the area correlator technique can provide a stable and accurate track of targets for use in airborne systems in conjunction with FLIR or TV imagers. It is a small size and can be built into standard format packages for installation in military aircraft. The main advantages of this technique are: (1) it can handle targets with a wide range of characteristics; (2) it can track background features to provide a ground reference; (3) it does not require that the edges of the target are within the tracking patches and it can handle targets which completely fill the field of view; (4) it can adapt automatically to magnification and target aspect changes; and (5) it provides highly tenacious tracking in low signal to noise conditions.

  7. TARGETING POLYMER THERAPEUTICS TO BONE

    PubMed Central

    Low, Stewart; Kope?ek, Jind?ich

    2012-01-01

    An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

  8. Auditory target detection in reverberation.

    PubMed

    Zurek, Patrick M; Freyman, Richard L; Balakrishnan, Uma

    2004-04-01

    Measurements and theoretical predictions of auditory target detection in simulated reverberant conditions are reported. The target signals were pulsed 1/3-octave bands of noise and the masker signal was a continuous wideband noise. Target and masker signals were passed through a software simulation of a reverberant room with a rigid sphere modeling a listener's head. The location of the target was fixed while the location of the masker was varied in the simulated room. Degree of reverberation was controlled by varying the uniform acoustic absorption of the simulated room's surfaces. The resulting target and masker signals were presented to the listeners over headphones in monaural-left, monaural-right, or binaural listening modes. Changes in detection performance in the monaural listening modes were largely predictable from the changes in target-to-masker ratio in the target band, but with a few dB of extra masking in reverberation. Binaural detection performance was generally well predicted by applying Durlach's [in Foundations of Modern Auditory Theory (Academic, New York, 1972)] equalization-cancellation theory to the direct-plus-reverberant ear signals. Predictions in all cases were based on a statistical description of room acoustics and on acoustic diffraction by a sphere. The success of these detection models in the present well-controlled reverberant conditions suggests that they can be used to incorporate listening mode and source location as factors in speech-intelligibility predictions. PMID:15101640

  9. Targeted Therapies for Lung Cancer

    PubMed Central

    Larsen, Jill E.; Cascone, Tina; Gerber, David E.; Heymach, John V.; Minna, John D.

    2012-01-01

    Although lung cancer remains the leading cancer killer in the United States, recently a number of developments indicate future clinical benefit. These include evidence that computed tomography–based screening decreases lung cancer mortality, the use of stereotactic radiation for early-stage tumors, the development of molecular methods to predict chemotherapy sensitivity, and genome-wide expression and mutation analysis data that have uncovered oncogene “addictions” as important therapeutic targets. Perhaps the most significant advance in the treatment of this challenging disease is the introduction of molecularly targeted therapies, a term that currently includes monoclonal antibodies and small-molecule tyrosine kinase inhibitors. The development of effective targeted therapeutics requires knowledge of the genes and pathways involved and how they relate to the biologic behavior of lung cancer. Drugs targeting the epidermal growth factor receptor, anaplastic lymphoma kinase, and vascular endothelial growth factor are now U.S. Food and Drug Administration approved for the treatment of advanced non-small cell lung cancer. These agents are generally better tolerated than conventional chemotherapy and show dramatic efficacy when their use is coupled with a clear understanding of clinical data, mechanism, patient selection, drug interactions, and toxicities. Integrating genome-wide tumor analysis with drug- and targeted agent-responsive phenotypes will provide a wealth of new possibilities for lung cancer–targeted therapeutics. Ongoing research efforts in these areas as well as a discussion of emerging targeted agents being evaluated in clinical trials are the subjects of this review. PMID:22157296

  10. The JENSA Gas Jet Target

    NASA Astrophysics Data System (ADS)

    Chipps, K. A.

    2014-03-01

    With the construction of next-generation radioactive ion beam (RIB) facilities, the study of many rare and unstable isotopes previously unattainable will be made possible. In order to take full advantage of possible measurements with these new isotope beams, improvements in detectors and targets are necessary. The Jet Experiments in Nuclear Structure and Astrophysics (JENSA) gas jet target is a new and cutting-edge target system, designed to provide a target of light gas, such as hydrogen or helium, that is localized, dense, and pure. In order to accomplish this, the JENSA system involves nearly two dozen vacuum pumps, differential pumping stages, a custom-built industrial compressor, and vacuum chambers designed to incorporate large arrays of both charged-particle and gamma-ray detectors. The JENSA gas jet target was originally constructed and characterized at ORNL, and has now moved to the ReA3 hall at the NSCL. Tests at ORNL show the JENSA system is capable of producing the most dense helium jet target for RIB studies in the world. JENSA will form the main target for the proposed SEparator for CApture Reactions (SECAR), and together the two comprise the equipment necessary to facilitate the studies which form the focus of the U.S. experimental nuclear astrophysics community. Work funded by US DOE Office of Science and the NSF.

  11. 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.

  12. Targeted Therapies in Lung Cancer

    PubMed Central

    Chirieac, Lucian R.; Dacic, Sanja

    2010-01-01

    An ongoing research and multiple clinical trials involve new targeted therapies and less aggressive treatment regimens that improve survival in patients with lung cancer. Targeted therapeutic agents are based on the concept of discovering genetic alterations and the signaling pathways altered in cancer and have added significantly to our armamentarium in order to prolong patient survival and minimizing drug toxicity. Among 34 molecularly targeted drugs approved by U.S. Food and Drug Administration (FDA) for treatment of various cancers since 1998 three targeted therapies have been approved for treatment of lung cancer (gefitinib in 2002, erlotinib in 2003, and bevacizumab in 2006). This review focuses on the targeted therapies in lung cancer, the molecular biomarkers that help identify patients that will benefit for these targeted therapies, describes the basic molecular biology principles and selected molecular diagnostic techniques and the pathological features correlated with molecular abnormalities in lung cancer. Lastly, new molecular abnormalities described in lung cancer that are predictive to novel promising targeted agents in various phases of clinical trials are discussed. PMID:20680095

  13. ORNL gas-jet target

    SciTech Connect

    Thornton, S.T.; Parks, R.L.; Shapira, D.; Ford, J.L.C. Jr.; Shivakumar, B.; Novotny, R.

    1984-01-01

    A supersonic gas jet target built for studying heavy-ion induced nuclear reactions with high energy resolution is described. The device is installed as part of a magnetic spectrograph and has produced image sizes in the focal plane as small as 0.4 mm using 100 MeV /sup 16/O beams collimated to an area of about 1 mm/sup 2/. Target densities of 30 ..mu..g/cm/sup 2/ (/sup 40/Ar) and 15 ..mu..g/cm/sup 2/ (/sup 14/N) have easily been obtained. The target has already been used for two nuclear reaction experiments. 9 references, 8 figures.

  14. Versatile cold atom target apparatus

    SciTech Connect

    Goetz, Simone; Hoeltkemeier, Bastian; Hofmann, Christoph S.; Litsch, Dominic; DePaola, Brett D.; Weidemueller, Matthias

    2012-07-15

    We report on a compact and transportable apparatus that consists of a cold atomic target at the center of a high resolution recoil ion momentum spectrometer. Cold rubidium atoms serve as a target which can be operated in three different modes: in continuous mode, consisting of a cold atom beam generated by a two-dimensional magneto-optical trap, in normal mode in which the atoms from the beam are trapped in a three-dimensional magneto-optical trap (3D MOT), and in high density mode in which the 3D MOT is operated in dark spontaneous optical trap configuration. The targets are characterized using photoionization.

  15. Targeted biopharmaceuticals for cancer treatment.

    PubMed

    Zhou, Lufang; Xu, Ningning; Sun, Yan; Liu, Xiaoguang Margaret

    2014-10-01

    Cancer is a complex invasive genetic disease that causes significant mortality rate worldwide. Protein-based biopharmaceuticals have significantly extended the lives of millions of cancer patients. This article reviews the biological function and application of targeted anticancer biopharmaceuticals. We first discuss the specific antigens and core pathways that are used in the development of targeted cancer therapy. The innovative monoclonal antibodies, non-antibody proteins, and small molecules targeting these antigens or pathways are then reviewed. Finally, the current challenges in anticancer biopharmaceuticals development and the potential solutions to address these challenges are discussed. PMID:25016064

  16. A variable optical target simulator

    NASA Technical Reports Server (NTRS)

    Kulas, C. E.; Crosswhite, E. D.

    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 optical target simulator. An optomechanical device called a Variable Optical Target Simulator (VOTS) which generates end game scene situations is discussed. The organization of optical components and their control for providing an image which grows in size as a linear estimate of real world situations is presented.

  17. Targetry overview — Various target concepts and expectable next generation targets in power frontier applications —

    NASA Astrophysics Data System (ADS)

    Futakawa, Masatoshi

    Present operational status of the target systems in accelerators based facilities and challenging R&D to the high power frontier target concepts will be introduced. The features of various target systems; stationary solid targets, rotated targets, liquid metals targets, windowless targets, powder targets, etc. will be described from the viewpoints of thermal loading conditions, high strain rate effects, yielding effects, irradiation damage, effective methods of target cooling, lifetime, remote handling, safety, etc. Additionally, the issues for each target concept will be discussed.

  18. [Molecular targets in colon cancer].

    PubMed

    Borner, M M

    2006-04-01

    Colorectal cancer is the second leading cause of cancer death in Switzerland. The nihilism that dominated the treatment of these patients for decades has been replaced by a measure of enthusiasm, given recent therapeutic advances. New anticancer drugs such as irinotecan and oxaliplatin have changed the standard chemotherapy treatment of metastatic colorectal cancer. However, the real hype has come from molecular targeted therapy. Identification of cellular processes characteristic of colon cancer has permitted therapeutic targeting with favorable therapeutic index. Inhibition of the epidermal growth factor receptor in the clinic has provided proof of principle that interruption of signal transduction cascades in patients has therapeutic potential. Angiogenesis, especially the vascular endothelial growth factor pathway, has been proven to be another highly successful molecular target. In this article, we will review molecular targets, which are under active clinical investigation in colon cancer. PMID:16689454

  19. Inertial-confinement-fusion targets

    SciTech Connect

    Hendricks, C.D.

    1982-08-10

    Much of the research in laser fusion has been done using simple ball on-stalk targets filled with a deuterium-tritium mixture. The targets operated in the exploding pusher mode in which the laser energy was delivered in a very short time (approx. 100 ps or less) and was absorbed by the glass wall of the target. The high energy density in the glass literally exploded the shell with the inward moving glass compressing the DT fuel to high temperatures and moderate densities. Temperatures achieved were high enough to produce DT reactions and accompanying thermonuclear neutrons and alpha particles. The primary criteria imposed on the target builders were: (1) wall thickness, (2) sphere diameter, and (3) fuel in the sphere.

  20. Tumor targeting, trifunctional dendritic wedge.

    PubMed

    Dubey, Ramin; Kushal, Swati; Mollard, Alexis; Vojtovich, Lesya; Oh, Philip; Levin, Michael D; Schnitzer, Jan E; Zharov, Ilya; Olenyuk, Bogdan Z

    2015-01-21

    We report in vitro and in vivo evaluation of a newly designed trifunctional theranostic agent for targeting solid tumors. This agent combines a dendritic wedge with high boron content for boron neutron capture therapy or boron MRI, a monomethine cyanine dye for visible-light fluorescent imaging, and an integrin ligand for efficient tumor targeting. We report photophysical properties of the new agent, its cellular uptake and in vitro targeting properties. Using live animal imaging and intravital microscopy (IVM) techniques, we observed a rapid accumulation of the agent and its retention for a prolonged period of time (up to 7 days) in fully established animal models of human melanoma and murine mammary adenocarcinoma. This macromolecular theranostic agent can be used for targeted delivery of high boron load into solid tumors for future applications in boron neutron capture therapy. PMID:25350602

  1. SCF ubiquitin ligase targeted therapies

    PubMed Central

    Skaar, Jeffrey R.; Pagan, Julia K.; Pagano, Michele

    2015-01-01

    Summary The recent clinical successes of inhibitors of the proteasome for the treatment of cancer have highlighted the therapeutic potential of this protein degradation system. Proteasome inhibitors prevent the degradation of numerous proteins, so increased specificity could be achieved by inhibiting the components of the ubiquitin-proteasome system that target specific subsets of proteins for degradation. F-box proteins are the substrate-targeting subunits of SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes. Through the degradation of a plethora of diverse substrates, SCF ubiquitin ligases control a large number of processes at the cellular and organismal levels, and their misregulation is implicated in many pathologies. SCF ligases are characterized by a high specificity for their substrates, so they represent promising drug targets. However, the potential for therapeutic manipulation of SCF complexes remains an underdeveloped area. This review will explore and discuss potential strategies to target SCF-mediated biology to treat human diseases. PMID:25394868

  2. "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.

  3. Targeting ubiquitination for cancer therapies.

    PubMed

    Morrow, John Kenneth; Lin, Hui-Kuan; Sun, Shao-Cong; Zhang, Shuxing

    2015-11-01

    Ubiquitination, the structured degradation and turnover of cellular proteins, is regulated by the ubiquitin-proteasome system (UPS). Most proteins that are critical for cellular regulations and functions are targets of the process. Ubiquitination is comprised of a sequence of three enzymatic steps, and aberrations in the pathway can lead to tumor development and progression as observed in many cancer types. Recent evidence indicates that targeting the UPS is effective for certain cancer treatment, but many more potential targets might have been previously overlooked. In this review, we will discuss the current state of small molecules that target various elements of ubiquitination. Special attention will be given to novel inhibitors of E3 ubiquitin ligases, especially those in the SCF family. PMID:26630263

  4. Cavitation in a Mercury Target

    SciTech Connect

    West, C.D.

    2000-09-01

    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.

  5. 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.

  6. Modulation domain infrared target models

    NASA Astrophysics Data System (ADS)

    Havlicek, Joseph P.; Nguyen, Chuong T.; Yeary, Mark

    2006-05-01

    We compute joint AM-FM models that characterize infrared targets and backgrounds in the modulation domain. We consider spatially localized structures within an IR image as sums of nonstationary, quasi-sinusoidal functions admitting locally narrowband amplitude and frequency modulations. By quantitatively estimating the modulations that dominate the signal spectrum on a spatially local basis, we obtain a new modulation domain feature vector that can augment the more traditional pixel domain, Fourier spectrum, and multispectral color features that have been used in IR target detection and tracking systems for a long time. Our preliminary studies, based primarily on midwave and longwave missile approach sequences, suggest that IR targets and backgrounds do typically possess sufficient spatially local modulated structure (i.e., texture) for modulation domain techniques to be meaningfully applied. We also present qualitative results strongly indicating that the modulation domain feature vector is a powerful tool for discriminating infrared targets and backgrounds.

  7. Tumor Targeting, Trifunctional Dendritic Wedge

    PubMed Central

    2015-01-01

    We report in vitro and in vivo evaluation of a newly designed trifunctional theranostic agent for targeting solid tumors. This agent combines a dendritic wedge with high boron content for boron neutron capture therapy or boron MRI, a monomethine cyanine dye for visible-light fluorescent imaging, and an integrin ligand for efficient tumor targeting. We report photophysical properties of the new agent, its cellular uptake and in vitro targeting properties. Using live animal imaging and intravital microscopy (IVM) techniques, we observed a rapid accumulation of the agent and its retention for a prolonged period of time (up to 7 days) in fully established animal models of human melanoma and murine mammary adenocarcinoma. This macromolecular theranostic agent can be used for targeted delivery of high boron load into solid tumors for future applications in boron neutron capture therapy. PMID:25350602

  8. Overview of Target Enrichment Strategies.

    PubMed

    Kozarewa, Iwanka; Armisen, Javier; Gardner, Andrew F; Slatko, Barton E; Hendrickson, C L

    2015-01-01

    Target enrichment is commonly used in next generation sequencing (NGS) workflows to eliminate genomic DNA regions that are not of interest for a particular experiment. By only targeting specific regions such as exons, one can obtain greater depth of DNA sequencing coverage for regions of interest or increase the sampling numbers of individuals, thereby saving both time and cost. This overview of target enrichment strategies provides a high-level review of distinct approaches to capture specific sequences: (a) hybridization-based strategies, (b) transposon-mediated fragmentation (tagmentation), (c) molecular inversion probes (MIPs), and (d) singleplex and multiplex polymerase chain reaction (PCR) target enrichment. Strategies for assay design and performance criteria are also discussed. Other platforms currently in development are also briefly described. PMID:26423591

  9. Nanotechnology of emerging targeting systems.

    PubMed

    Smith, S S

    2008-09-01

    Recent developments in the design and testing of complex nanoscale payload-carrying systems (i.e. systems with payloads that do not exceed 100 nm in size) are the focus of this brief review. Emerging systems include targeted single-walled nanotubes, viral capsids, dendrimers, gold nanoparticles, milled boron carbide nanoparticles, and protein nucleic acid assemblies. Significant advances are emerging with each of these bionanotechnological approaches to cellular targeting. PMID:21687833

  10. Nanotechnology of emerging targeting systems

    PubMed Central

    SMITH, S. S.

    2011-01-01

    Recent developments in the design and testing of complex nanoscale payload-carrying systems (i.e. systems with payloads that do not exceed 100 nm in size) are the focus of this brief review. Emerging systems include targeted single-walled nanotubes, viral capsids, dendrimers, gold nanoparticles, milled boron carbide nanoparticles, and protein nucleic acid assemblies. Significant advances are emerging with each of these bionanotechnological approaches to cellular targeting. PMID:21687833

  11. The JLab Frozen Spin Target

    SciTech Connect

    Keith, C. D.

    2009-08-04

    A polarized, frozen spin target has been designed and constructed at Jefferson Lab for use inside the CEBAF Large Acceptance Spectrometer. Protons in TEMPO-doped butanol are polarized via dynamic nuclear polarization (DNP) to approximately 90% using microwaves and an external, 5 T solenoid magnet. The target sample is then cooled to approximately 30 mK while an internal 0.56 T superconducting magnet is used to maintain the polarization. Relaxation times in excess of 3500 hours have been observed.

  12. IPNS enriched uranium booster target

    SciTech Connect

    Schulke, A.W. Jr.

    1985-01-01

    Since startup in 1981, IPNS has operated on a fully depleted /sup 238/U target. With the booster as in the present system, high energy protons accelerated to 450 MeV by the Rapid Cycling Synchrotron are directed at the target and by mechanisms of spallation and fission of the uranium, produce fast neutrons. The neutrons from the target pass into adjacent moderator where they slow down to energies useful for spectroscopy. The target cooling systems and monitoring systems have operated very reliably and safely during this period. To provide higher neutron intensity, we have developed plans for an enriched uranium (booster) target. HETC-VIM calculations indicate that the target will produce approx.90 kW of heat, with a nominal x5 gain (k/sub eff/ = 0.80). The neutron beam intensity gain will be a factor of approx.3. Thermal-hydraulic and heat transport calculations indicate that approx.1/2 in. thick /sup 235/U discs are subject to about the same temperatures as the present /sup 238/U 1 in. thick discs. The coolant will be light demineralized water (H/sub 2/O) and the coolant flow rate must be doubled. The broadening of the fast neutron pulse width should not seriously affect the neutron scattering experiments. Delayed neutrons will appear at a level about 3% of the total (currently approx.0.5%). This may affect backgrounds in some experiments, so that we are assessing measures to control and correct for this (e.g., beam tube choppers). Safety analyses and neutronic calculations are nearing completion. Construction of the /sup 235/U discs at the ORNL Y-12 facility is scheduled to begin late 1985. The completion of the booster target and operation are scheduled for late 1986. No enriched uranium target assembly operating at the projected power level now exists in the world. This effort thus represents an important technological experiment as well as being a ''flux enhancer''.

  13. Target identification using laser imaging

    SciTech Connect

    Jennings, J.; Baker, M.; Barrett, J.; Ellis, B.N.; Kacerek, J.; Yee, J.

    1994-12-31

    Solid state lasers have been utilized for many varied applications. This application describes how the high peak power, short pulse capability of an alexandrite laser, in combination with a generation 3 image intensified receiver can solve the problem of very long range target identification. Applications have relevance to both commercial and military uses where day/night all weather imaging is required. Wavelength diversity provides single and multispectral system capability, therefore allowing discrimination of targets against varied backgrounds.

  14. Ion beam inertial confinement target

    DOEpatents

    Bangerter, Roger O.; Meeker, Donald J.

    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.

  15. Oral targeted therapy for cancer

    PubMed Central

    Carrington, Christine

    2015-01-01

    SUMMARY Oral targeted therapies are increasingly being used to treat cancer. They work by interfering with specific molecules or pathways involved in tumour growth. It is essential that health professionals managing patients taking these drugs have appropriate training and skills. They should be aware of potential adverse effects and drug interactions, and be able to manage toxicities when they occur. Despite the selectivity of these targeted therapies, they still have serious adverse effects including skin reactions, diarrhoea and altered organ function. PMID:26648656

  16. Target template precision is unaffected by target-distractor similarity.

    PubMed

    Wyland, Hannah; Vecera, Shaun

    2015-09-01

    It is well supported that target templates held in visual short-term memory guide visual search (Desimone & Duncan, 1995; Wolfe, 1994). We investigated how template precision is affected by search context. Following previous research, participants searched RSVP streams for an orange letter and reported its presence or absence (Anderson, 2014). In different blocks, distractor letters were either similar to the target color (red, gold, green and blue) or dissimilar to the target color (white, purple, green and blue). If template precision is affected by search difficulty, accuracy differences should be found between the two distractor conditions. In Experiments 1-3, the RSVP stream consisted of eight frames of four letters each. Targets in Experiment 1 could appear at any location on the 2nd-6th frames. Compared to the distractor dissimilar condition, accuracy in the similar distractor condition was significantly worse. This difference, however, may reflect insufficient time for selection and consolidation processes, not template precision. To test this, targets in Experiment 2 appeared on screens 4-8. While subsequent displays may interrupt processing of the 4th-7th screens, the 8th (final) screen allows adequate time for selection and consolidation. Here, a significant interaction was found between distractor color and target position with follow-up tests indicating significantly better performance at the 8th position in the similar distractor condition. For Experiment 3, additional time was added between each RSVP display to allow selection and consolidation of each display. Although the main effect of distractor color was significant, the accuracy difference between the conditions was greatly reduced. To remove the need for selection processes, Experiment 4 presented a single stream of 16 frames. Accuracy for this experiment did not differ between conditions. The results of these experiments suggest that target identification is limited by selection, consolidation, and comparison processes, but not by template precision. Meeting abstract presented at VSS 2015. PMID:26326134

  17. Killing cells by targeting mitosis

    PubMed Central

    Manchado, E; Guillamot, M; Malumbres, M

    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 killing cancer cells. Microtubule poisons have proved efficacy in the clinic against a broad range of malignancies, and novel targeted strategies are now evaluating the inhibition of critical activities, such as cyclin-dependent kinase 1, Aurora or Polo kinases or spindle kinesins. Abrogation of the mitotic checkpoint or targeting the energetic or proteotoxic stress of aneuploid or chromosomally instable cells may also provide further benefits by inducing lethal levels of instability. Although cancer cells may display different responses to these treatments, recent data suggest that targeting mitotic exit by inhibiting the anaphase-promoting complex generates metaphase cells that invariably die in mitosis. As the efficacy of cell–cycle targeting approaches has been limited so far, further understanding of the molecular pathways modulating mitotic cell death will be required to move forward these new proposals to the clinic. PMID:22223105

  18. 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

  19. Targeting Breast Cancer Stem Cells

    PubMed Central

    McDermott, Sean P.; Wicha, Max S.

    2010-01-01

    The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. Although, the CSC hypothesis does not directly address the cell of origin of cancer, it is postulated that tissue-resident stem or progenitors are the most common targets of transformation. Clinically, CSCs are predicted to mediate tumor recurrence after chemo- and radiation-therapy due to the relative inability of these modalities to effectively target CSCs. If this is the case, then CSC must be efficiently targeted to achieve a true cure. Similarities between normal and malignant stem cells, at the levels of cell-surface proteins, molecular pathways, cell cycle quiescence, and microRNA signaling present challenges in developing CSC-specific therapeutics. Approaches to targeting CSCs include the development of agents targeting known stem cell regulatory pathways as well as unbiased high-throughput siRNA or small-molecule screening. Based on studies of pathways present in normal stem cells, recent work has identified potential “Achilles heals” of CSC, whereas unbiased screening provides opportunities to identify new pathways utilized by CSC as well as develop potential therapeutic agents. Here, we review both approaches and their potential to effectively target breast CSC. PMID:20599450

  20. Radiation target analysis of RNA.

    PubMed

    Benstein, S L; Kempner, E

    1996-06-25

    Ribozymes are polynucleotide molecules with intrinsic catalytic activity, capable of cleaving nucleic acid substrates. Large RNA molecules were synthesized containing a hammerhead ribozyme moiety of 52 nucleotides linked to an inactive leader sequence, for total lengths of either 262 or 1226 nucleotides. Frozen RNAs were irradiated with high energy electrons. Surviving ribozyme activity was determined using the ability of the irradiated ribozymes to cleave a labeled substrate. The amount of intact RNA remaining was determined from the same irradiated samples by scanning the RNA band following denaturing gel electrophoresis. Radiation target analyses of these data revealed a structural target size of 80 kDa and a ribozyme activity target size of 15 kDa for the smaller ribozyme, and 319 kDa and 16 kDa, respectively, for the larger ribozyme. The disparity in target size for activity versus structure indicates that, in contrast to proteins, there is no spread of radiation damage far from the primary site of ionization in RNA molecules. The smaller target size for activity indicates that only primary ionizations occurring in the specific active region are effective. This is similar to the case for oligosaccharides. We concluded that the presence of the ribose sugar in the polymer chain restricts radiation damage to a small region and prevents major energy transfer throughout the molecule. Radiation target analysis should be a useful technique for evaluating local RNA:RNA and RNA:protein interactions in vitro. PMID:8692828

  1. Targeting STATs for cancer therapy

    PubMed Central

    Frank, David A.

    2012-01-01

    We are in the midst of an exciting transition in the treatment of cancers, from the empirically developed non-specifically cytotoxic drugs to the era of rationally derived molecularly targeted therapies. Over the past 15 years, our understanding of the mutations that drive cancer pathogenesis has grown enormously, which has rapidly led to the development of drugs to target the associated gene products. Almost all of this focus has been on kinases, largely tyrosine kinases that are activated by translocations, point mutations, insertions and deletions. Although this approach will continue to bear fruit for some time, there is increasing evidence that the returns will be diminishing. First, dominant activating mutations in kinases are less frequent then initially expected particularly in common human cancers, and thus the number of patient whose tumors have suitable targets may be limited. The second cause for concern is the rapid development of resistance that often occurs, arising either from mutations in the target kinase or activation of a parallel pathway. Thus, the desire to target a common convergence point of multiple pathways that directly contributes to the oncogenic phenotype is highly desirable. This goal has led to consideration of transcription factors as therapeutic targets. PMID:24058782

  2. Killing cells by targeting mitosis.

    PubMed

    Manchado, E; Guillamot, M; Malumbres, M

    2012-03-01

    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 killing cancer cells. Microtubule poisons have proved efficacy in the clinic against a broad range of malignancies, and novel targeted strategies are now evaluating the inhibition of critical activities, such as cyclin-dependent kinase 1, Aurora or Polo kinases or spindle kinesins. Abrogation of the mitotic checkpoint or targeting the energetic or proteotoxic stress of aneuploid or chromosomally instable cells may also provide further benefits by inducing lethal levels of instability. Although cancer cells may display different responses to these treatments, recent data suggest that targeting mitotic exit by inhibiting the anaphase-promoting complex generates metaphase cells that invariably die in mitosis. As the efficacy of cell-cycle targeting approaches has been limited so far, further understanding of the molecular pathways modulating mitotic cell death will be required to move forward these new proposals to the clinic. PMID:22223105

  3. Radiation target analysis of RNA.

    PubMed Central

    Benstein, S L; Kempner, E

    1996-01-01

    Ribozymes are polynucleotide molecules with intrinsic catalytic activity, capable of cleaving nucleic acid substrates. Large RNA molecules were synthesized containing a hammerhead ribozyme moiety of 52 nucleotides linked to an inactive leader sequence, for total lengths of either 262 or 1226 nucleotides. Frozen RNAs were irradiated with high energy electrons. Surviving ribozyme activity was determined using the ability of the irradiated ribozymes to cleave a labeled substrate. The amount of intact RNA remaining was determined from the same irradiated samples by scanning the RNA band following denaturing gel electrophoresis. Radiation target analyses of these data revealed a structural target size of 80 kDa and a ribozyme activity target size of 15 kDa for the smaller ribozyme, and 319 kDa and 16 kDa, respectively, for the larger ribozyme. The disparity in target size for activity versus structure indicates that, in contrast to proteins, there is no spread of radiation damage far from the primary site of ionization in RNA molecules. The smaller target size for activity indicates that only primary ionizations occurring in the specific active region are effective. This is similar to the case for oligosaccharides. We concluded that the presence of the ribose sugar in the polymer chain restricts radiation damage to a small region and prevents major energy transfer throughout the molecule. Radiation target analysis should be a useful technique for evaluating local RNA:RNA and RNA:protein interactions in vitro. Images Fig. 2 PMID:8692828

  4. 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.

  5. [Pasteurella canis hemorragic sepsis and empyema].

    PubMed

    Casallas-Rivera, Martha; Faccini-Martínez, Álvaro; Perdomo-Beltrán, Natalia; Botero-García, Carlos; Bravo, Juan; Pérez-Díaz, Carlos

    2016-02-01

    We report the case of a 56-year-old female patient, with a three-day history of hematemesis, melena, abdominal wall hematoma and epistaxis associated with thrombocytopenia and anemia. Idiopathic thrombocytopenic purpura was diagnosed and she was treated with dexamethasone for four days. The patient developed acute respiratory failure with signs of systemic inflammatory response. Blood and pleural fluid cultures grew Pasteurella canis. This is the first case, to our knowledge, of P. canis empyema associated with hemorrhagic septicemia without epidemiological background and the third case of septicemia caused by P. canis reported in the literature. PMID:26965885

  6. Pathophysiology of tumour-induced microangiopathic haemolytic anaemia.

    PubMed

    Chalasani, Pavani; Segar, Jennifer M; Marron, Marilyn; Stopeck, Alison

    2016-01-01

    Cancer-associated microangiopathic haemolytic anaemia (CA-MAHA) is a syndrome characterised by Coombs-negative haemolytic anaemia and thrombocytopenia. It is primarily seen in advanced solid tumours and is distinct from thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome. Diagnosis is often delayed and patients have a high mortality. We present the case of CA-MAHA in a patient with metastatic breast cancer treated successfully with early initiation of chemotherapy. In addition, we report longitudinal laboratory evaluation of circulating tumour cells and microparticles and suggest a hypothesis for the mechanism behind CA-MAHA. PMID:26744538

  7. Carbamazepine-induced Stevens-Johnson syndrome treated with IV steroids and IVIG.

    PubMed

    Straussberg, R; Harel, L; Ben-Amitai, D; Cohen, D; Amir, J

    2000-03-01

    A 17-year-old female is presented who developed antiepileptic drug hypersensitivity syndrome after treatment with carbamazepine. The initial diagnoses were idiopathic thrombocytopenic purpura and toxic shock syndrome. The patient was treated with intravenous immunoglobulin and intravenous steroids. After a severe climax on days 2-4 she recovered completely and was discharged on the eighth day of hospitalization. Although we do not have direct proof, we believe that these treatment modalities, especially the IVIG, shortened and ameliorated the clinical course of the disease. PMID:10734256

  8. [Thrombotic microangiopathy: when time is the key factor!].

    PubMed

    Hemett, O M; Martins, F; Descombes, E; Betticher, D; Hayoz, D

    2014-04-01

    Thrombotic microangiopathy or "TMA" including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) became a public health problem following the European outbreak of E. coli (O104:H4) gastroenteritis in 2011. A rapid diagnosis and therapy in an intensive care unit provide better patient survival and lower cost for society. Supportive treatment has significantly improved the prognosis over the past decade and includes fresh frozen plasma for TTP, plasmapheresis for HUS, and recently a new therapeutic agent: anti-C5 antibodies. We will provide in this article, through the current literature and four cases encountered in our department, to establish an algorithm to manage patients with TMA. PMID:24791425

  9. [Unusual autoimmune and neoplastic associated diseases in Sjogren's syndrome].

    PubMed

    Reiner, M; Goldhirsch, A; Kaplan, E; Luscieti, P; Pedrinis, E; Noseda, G

    1979-11-24

    In an unselected series of 12 patients with Sjögren's syndrome the following autoimmune diseases were observed: severe myxedema due to Hashimotos thyroiditis in four, subclinical thyroid hypofunction in one, diffuse hyperthyroidism in one, glomerulonephritis in two, chronic active hepatitis in one, lupus erythematodes disseminatus in three (one with idiopathic thrombocytopenic purpura), classical rheumatoid arthritis in two. A rare familial occurrence was seen in two sisters. The only male in this group exhibited coexistence of a benign adenolymphoma of the parotid gland (Warthin's tumor) with a malignant non-Hodgkin lymphoma. PMID:583182

  10. Thrombocytopenia-Associated Multiple Organ Failure and Acute Kidney Injury.

    PubMed

    Nguyen, Trung C; Cruz, Miguel A; Carcillo, Joseph A

    2015-10-01

    Thrombocytopenia-associated multiple organ failure (TAMOF) is a clinical phenotype that encompasses a spectrum of syndromes associated with disseminated microvascular thromboses, such as the thrombotic microangiopathies thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) and disseminated intravascular coagulation (DIC). Autopsies findings in TTP, HUS, or DIC reveal specific findings that can differentiate these 3 entities. Von Willebrand factor and ADAMTS-13 play a central role in TTP. Shiga toxins and the complement pathway are vital in the development of HUS. Tissue factor is the major protease that drives the pathology of DIC. Acute kidney injury (AKI) is a common feature in patients with TAMOF. PMID:26410136

  11. [Research advance on frozen injury and protective mechanisms of cryopreservated platelets].

    PubMed

    Yi, Xiao-Yang; Wang, Yan; Han, Ying

    2014-12-01

    Platelets are important component in the blood which play vital role in physiological hemostasis. In clinic, platelets are usually transfused to patients suffered from idiopathic thrombocytopenic purpura,thrombocytopenia after chemotherapy and radiotherapy,or hemorrhagic thrombocytopenia caused by other reasons. Storage time for platelet concentrates is limited to five days at room temperature, leading to an increasing number of scrap rate, therefore the prolonging the storage time is important for clinical application. Storage at -80°C is an ideal long-term cryopreservation method for platelet concentrates. In this article, platelets cryopreservation,the mechanism of frozen injury and the protective mechanisms of platelets were reviewed. PMID:25543512

  12. [Severe thrombocytopenia after diagnosis of deep venous thrombosis].

    PubMed

    Frøslev-Friis, Christina; Kliment, Herbert; Andersen, Johnny Dohn Holmgren

    2013-08-12

    A patient presented with erysipelas and developed deep venous thrombosis (DVT) and later idiopatic thrombocytopenic purpura (ITP). In the literature we find no reports of ITP following DVT. It is well known that patients can develop HIT after DVT or DVT after ITP, both caused by the medicine used for treatment. Patients have developed ITP after heparin-induced thrombocytopenia (HIT). Cases are also described in which heparin antibodies are found, but in which the final diagnosis was ITP. The diagnosis of the patient in our case story could be ITP based on DVT, but with no history of HIT. Alternatively, he could have developed two complications to an infection. PMID:23937877

  13. 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.

  14. Target identification using drug affinity responsive target stability (DARTS)

    PubMed Central

    Lomenick, Brett; Jung, Gwanghyun; Wohlschlegel, James A.; Huang, Jing

    2011-01-01

    Drug Affinity Responsive Target Stability is a general methodology for identifying and studying protein-ligand interactions. The technique is based on the principle that when a small molecule compound binds to a protein, the interaction stabilizes the target protein’s structure such that it becomes protease resistant. DARTS is particularly useful for the initial identification of the protein targets of small molecules, but can also be used to validate potential protein-ligand interactions predicted or identified by other means and to estimate the affinity of interactions. The approach is simple and advantageous because it can be performed using crude cell lysates and other complex protein mixtures (without requiring purified proteins), and uses native, unmodified small molecules. The protocols provided in this article describe the general approach for performing DARTS experiments, which can be easily modified and scaled to fit the criteria and purpose of any individual project. PMID:22229126

  15. Thrombocytopenia and Cornelia de Lange syndrome: Still an enigma?

    PubMed

    Cavalleri, Valeria; Bettini, Laura R; Barboni, Chiara; Cereda, Anna; Mariani, Milena; Spinelli, Marco; Gervasini, Cristina; Russo, Silvia; Biondi, Andrea; Jankovic, Momcilo; Selicorni, Angelo

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder caused by mutations in the cohesion complex and its regulators. The syndrome is characterized by multiple organ system abnormalities, pre- and post-natal growth retardation and typical facial features. Thrombocytopenia is a reduction in platelet count to <150 × 10(9)  L. It can be caused by congenital or acquired decreased production, increased destruction, or sequestration of platelets. In recent years, several papers reported thrombocytopenia and immune thrombocytopenia in patients affected by CdLS. In 2011, Lambert et al. estimated the risk of idiopathic thrombocytopenia purpura in CdLS patients to be 31-633 times greater than in the general population. We describe the incidence of thrombocytopenia in 127 Italian CdLS patients, identifying patients with transient or persistent thrombocytopenia, but a lower incidence of true idiopathic thrombocytopenic purpura (ITP). © 2015 Wiley Periodicals, Inc. PMID:26437745

  16. Targeted therapy for breast cancer.

    PubMed

    Mohamed, Ali; Krajewski, Kenneth; Cakar, Burcu; Ma, Cynthia X

    2013-10-01

    Breast cancer is a heterogeneous group of diseases that are clinically subdivided as hormone receptor-positive, human epidermal growth factor receptor 2-positive (HER2(+)), and triple-negative breast cancer, to guide therapeutic interventions. Agents that target estrogen receptor (ER) and HER2 are among the most successful cancer therapeutics. However, de novo or acquired resistance is common, despite the development of newer agents against these pathways. As our understanding of tumor biology improves, novel targets are being identified. Notably, inhibitors against several pathways [including, among others, the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR), cell-cycle regulation, heat shock protein, and epigenetic pathways] have demonstrated promising activity in clinical trials, and the mTOR-inhibitor everolimus has been approved for advanced or metastatic aromatase inhibitor-resistant ER(+) breast cancer. At present, there are no established targeted agents for triple-negative breast cancer (negative ER, progesterone receptor, and HER2). Although poly(ADP-ribose) polymerase inhibitors have shown promising activity in BRCA-related cancers, its value in the treatment of triple-negative breast cancers remains to be demonstrated. In this Review, we present a basic understanding of the major targeted agents in current practice and under development for the treatment of breast cancer in the context of the three clinical subgroups. PMID:23988612

  17. Antibody-drug conjugate targets.

    PubMed

    Teicher, B A

    2009-12-01

    The requirements for a cell surface molecule to be suitable as an antibody-drug conjugate target are stringent. The notion that antibodies-directed toward targets on the surface of malignant cells could be used for drug delivery is not new. The history of antibody-drug conjugates has been marked by hurdles identified and overcome. Early conjugates used mouse antibodies, drugs that were either not sufficiently potent, were immunogenic (proteins) or were too toxic and linkers that were not sufficiently stable in circulation. Three main avenues have been explored using antibodies to target cytotoxic species to malignant cells, antibody-protein toxin conjugates (or antibody fragment-protein toxin fusion proteins), antibody-small molecule drug conjugates and antibody-enzyme conjugates administered along with small molecule prodrugs requiring metabolism by the conjugated enzyme to release the activate species. This review focuses on cell surface proteins that have been targeted primarily by antibody-small molecule drug conjugates and briefly discusses 34 targets being investigated. While only one antibody-drug conjugate has reached regulatory approval, there are nearly 20 of these in clinical trial. The time may have come for this technology to become a major contributor to improving treatment for cancer patients. PMID:20025606

  18. Antiproton stopping in atomic targets

    NASA Astrophysics Data System (ADS)

    Bailey, J. J.; Kadyrov, A. S.; Abdurakhmanov, I. B.; Fursa, D. V.; Bray, I.

    2015-08-01

    Stopping powers of antiprotons in H, He, Ne, Ar, Kr, and Xe targets are calculated using a semiclassical time-dependent convergent close-coupling method. The helium target is treated using both frozen-core and multiconfiguration approximations. The electron-electron correlation of the target is fully accounted for in both cases. Double ionization and ionization with excitation channels are taken into account using an independent-event model. The Ne, Ar, Kr, and Xe atom wave functions are described in a model of six p -shell electrons above a frozen Hartree-Fock core with only one-electron excitations from the outer p shell allowed. Results obtained for helium in the multiconfiguration treatment are in better agreement with experimental measurements than other theories.

  19. Novel Targets for Antidepressant Therapies

    PubMed Central

    Holtzheimer, Paul E.; Nemeroff, Charles B.

    2015-01-01

    Most depressed patients fail to achieve remission despite adequate antidepressant monotherapy, and a substantial minority show minimal improvement despite optimal and aggressive therapy. However, major advances have taken place in elucidating the neurobiology of depression, and several novel targets for antidepressant therapy have emerged. Three primary approaches are currently being taken: 1) optimizing the pharmacologic modulation of monoaminergic neurotransmission, 2) developing medications that target neurotransmitter systems other than the monoamines, and 3) directly modulating neuronal activity via focal brain stimulation. We review novel therapeutic targets for developing improved antidepressant therapies, including triple monoamine reuptake inhibitors, atypical antipsychotic augmentation, dopamine receptor agonists, corticotropin-releasing factor-1 receptor antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, N-methyl-D-aspartate receptor antagonists, nemifitide, omega-3 fatty acids, and melatonin receptor agonists. Developments in therapeutic focal brain stimulation include vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, and deep brain stimulation. PMID:18980729

  20. 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

  1. Thermal Targets for Satellite Calibration

    SciTech Connect

    Villa-Aleman, E.

    2001-01-10

    The Savannah River Technology Center (SRTC) is currently calibrating the Multispectral Thermal Imager (MTI) satellite sponsored by the Department of Energy. The MTI imager is a research and development project with 15 wavebands in the visible, near-infrared, short-wave infrared, mid-wave infrared and long-wave infrared spectral regions. A plethora of targets with known temperatures such as power plant heated lakes, volcano lava vents, desert playas and aluminized Mylar tarps are being used in the validation of the five thermal bands of the MTI satellite. SRTC efforts in the production of ''cold targets'' with aluminized Mylar tarps will be described. Visible and thermal imagery and wavelength dependent radiance measurements of the calibration targets will be presented.

  2. 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

  3. Targeted therapies for breast cancer

    PubMed Central

    Higgins, Michaela J.; Baselga, José

    2011-01-01

    In recent years the description of well-defined molecular subtypes of breast cancer, together with the identification of the driving genetic alterations and signaling pathways, has led to the clinical development of a number of successful molecular targeted agents. This is best exemplified in the subset of HER2-amplified breast cancers, in which an increasing number of active agents are changing the natural history of this aggressive disease. Other targets are under exploration, and the clinical development of these agents will require a change from the current large, randomized trials in unselected patient populations to smaller trials in groups with a molecularly defined tumor type. In addition, combinatorial approaches that act on the secondary mutations and/or compensatory pathways in resistant tumors may markedly improve on the effects of targeted agents used alone. PMID:21965336

  4. A cryogenic infrared calibration target

    NASA Astrophysics Data System (ADS)

    Wollack, E. J.; Kinzer, R. E.; Rinehart, S. A.

    2014-04-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R ? 0.003, from 800 to 4800 cm-1 (12 - 2 ?m). Upon expanding the spectral range under consideration to 400-10 000 cm-1 (25 - 1 ?m) the observed performance gracefully degrades to R ? 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 ˜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.

  5. A cryogenic infrared calibration target.

    PubMed

    Wollack, E J; Kinzer, R E; Rinehart, S A

    2014-04-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R ? 0.003, from 800?to?4800?cm(-1) (12 - 2??m). Upon expanding the spectral range under consideration to 400-10,000?cm(-1) (25 - 1??m) the observed performance gracefully degrades to R ? 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 ?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. PMID:24784638

  6. Progress with developing a target for magnetized target fusion

    SciTech Connect

    Wysocki, F.J.; Chrien, R.E.; Idzorek, G.; Oona, H.; Whiteson, D.O.; Kirkpatrick, R.C.; Lindemuth, I.R.; Sheehey, P.T.

    1997-09-01

    Magnetized Target Fusion (MTF) is an approach to fusion where a preheated and magnetized plasma is adiabatically compressed to fusion conditions. Successful MTF requires a suitable initial target plasma with an embedded magnetic field of at least 5 T in a closed-field-line topology, a density of roughly 10{sup 18} cm{sup {minus}3}, a temperature of at least 50 eV, and must be free of impurities which would raise radiation losses. Target plasma generation experiments are underway at Los Alamos National Laboratory using the Colt facility; a 0.25 MJ, 2--3 {micro}s rise-time capacitor bank. The goal of these experiments is to demonstrate plasma conditions meeting the minimum requirements for a MTF initial target plasma. In the first experiments, a Z-pinch is produced in a 2 cm radius by 2 cm high conducting wall using a static gas-fill of hydrogen or deuterium gas in the range of 0.5 to 2 torr. Thus far, the diagnostics include an array of 12 B-dot probes, framing camera, gated OMA visible spectrometer, time-resolved monochrometer, filtered silicon photodiodes, neutron yield, and plasma-density interferometer. These diagnostics show that a plasma is produced in the containment region that lasts roughly 10 to 20 {micro}s with a maximum plasma density exceeding 10{sup 18} cm{sup {minus}3}. The experimental design and data are presented.

  7. 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.

  8. High-efficiency target-ion sources for RIB generation

    SciTech Connect

    Alton, G.D.

    1993-12-31

    A brief review is given of high-efficiency ion sources which have been developed or are under development at ISOL facilities which show particular promise for use at existing, future, or radioactive ion beam (RIB) facilities now under construction. Emphasis will be placed on those sources which have demonstrated high ionization efficiency, species versatility, and operational reliability and which have been carefully designed for safe handling in the high level radioactivity radiation fields incumbent at such facilities. Brief discussions will also be made of the fundamental processes which affect the realizable beam intensities in target-ion sources. Among the sources which will be reviewed will be selected examples of state-of-the-art electron-beam plasma-type ion sources, thermal-ionization, surface-ionization, ECR, and selectively chosen ion source concepts which show promise for radioactive ion beam generation. A few advanced, chemically selective target-ion sources will be described, such as sources based on the use of laser-resonance ionization, which, in principle, offer a more satisfactory solution to isobaric contamination problems than conventional electromagnetic techniques. Particular attention will be given to the sources which have been selected for initial or future use at the Holifield Radioactive Ion Beam Facility now under construction at the Oak Ridge National Laboratory.

  9. Materials considerations in accelerator targets

    SciTech Connect

    Peacock, H.B. Jr.; Iyer, N.C.; Louthan, M.R. Jr.

    1994-08-01

    Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from the coextruded product was modeled from experimental and operational data. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes the manufacturing technologies evaluated and presents the model for tritium retention in aluminum clad, aluminum-lithium alloy tritium production targets.

  10. Materials considerations in accelerator targets

    SciTech Connect

    Peacock, H. B. Jr.; Iyer, N. C.; Louthan, M. R. Jr.

    1995-09-15

    Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from, the coextruded product was modeled from experimental and operational data. The model assumed that tritium atoms, formed by the 6Li(n,a)3He reaction, were produced in solid solution in the Al-Li alloy. Because of the low solubility of hydrogen isotopes in aluminum alloys, the irradiated Al-Li rapidly became supersaturated in tritium. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes the manufacturing technologies evaluated and presents the model for tritium retention in aluminum clad, aluminum-lithium alloy tritium production targets.

  11. Dynamics of aerial target pursuit

    NASA Astrophysics Data System (ADS)

    Pal, S.

    2015-12-01

    During pursuit and predation, aerial species engage in multitasking behavior that involve simultaneous target detection, tracking, decision-making, approach and capture. The mobility of the pursuer and the target in a three dimensional environment during predation makes the capture task highly complex. Many researchers have studied and analyzed prey capture dynamics in different aerial species such as insects and bats. This article focuses on reviewing the capture strategies adopted by these species while relying on different sensory variables (vision and acoustics) for navigation. In conclusion, the neural basis of these capture strategies and some applications of these strategies in bio-inspired navigation and control of engineered systems are discussed.

  12. TARGETED DELIVERY OF INHALED PROTEINS

    EPA Science Inventory

    ETD-02-047 (Martonen) GPRA # 10108

    TARGETED DELIVERY OF INHALED PROTEINS
    T. B. Martonen1, J. Schroeter2, Z. Zhang3, D. Hwang4, and J. S. Fleming5
    1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park...

  13. Foam shell cryogenic ICF target

    DOEpatents

    Darling, Dale H. (Pleasanton, CA)

    1987-01-01

    A uniform cryogenic layer of DT fuel is maintained in a fusion target having a low density, small pore size, low Z rigid foam shell saturated with liquid DT fuel. Capillary action prevents gravitational slumping of the fuel layer. The saturated shell may be cooled to produce a solid fuel layer.

  14. 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

  15. Treatment targets in intracerebral hemorrhage.

    PubMed

    Sangha, Navdeep; Gonzales, Nicole R

    2011-07-01

    Intracerebral hemorrhage (ICH) imparts a higher mortality and morbidity than ischemic stroke. The therapeutic interventions that are currently available focus mainly on supportive care and secondary prevention. There is a paucity of evidence to support any one acute intervention that improves functional outcome. This chapter highlights current treatment targets for ICH based on the pathophysiology of the disease. PMID:21732225

  16. Raw eggs-moving target

    NASA Astrophysics Data System (ADS)

    Forrest, Doug

    1999-09-01

    High school physics students often have difficulty with understanding when and where to use an appropriate calculation to solve a problem. In this activity students have to solve a real problem using formulas they have seen before, but in a context with which they are unfamiliar; namely dropping a raw egg on a moving target-their instructor.

  17. Other targeted drugs in melanoma.

    PubMed

    González-Cao, María; Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-10-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are "targeted" to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other "druggable" kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials. PMID:26605312

  18. Targeted nanoparticles in mitochondrial medicine.

    PubMed

    Pathak, Rakesh K; Kolishetti, Nagesh; Dhar, Shanta

    2015-01-01

    Mitochondria, the so-called 'energy factory of cells' not only produce energy but also contribute immensely in cellular mortality management. Mitochondrial dysfunctions result in various diseases including but not limited to cancer, atherosclerosis, and neurodegenerative diseases. In the recent years, targeting mitochondria emerged as an attractive strategy to control mitochondrial dysfunction-related diseases. Despite the desire to direct therapeutics to the mitochondria, the actual task is more difficult due to the highly complex nature of the mitochondria. The potential benefits of integrating nanomaterials with properties such as biodegradability, magnetization, and fluorescence into a single object of nanoscale dimensions can lead to the development of hybrid nanomedical platforms for targeting therapeutics to the mitochondria. Only a handful of nanoparticles based on metal oxides, gold nanoparticles, dendrons, carbon nanotubes, and liposomes were recently engineered to target mitochondria. Most of these materials face tremendous challenges when administered in vivo due to their limited biocompatibility. Biodegradable polymeric nanoparticles emerged as eminent candidates for effective drug delivery. In this review, we highlight the current advancements in the development of biodegradable nanoparticle platforms as effective targeting tools for mitochondrial medicine. PMID:25348382

  19. Therapeutic targets for premature ejaculation.

    PubMed

    Andersson, Karl-Erik; Abdel-Hamid, Ibrahim A

    2011-09-01

    Premature ejaculation (PE) is the most common male sexual complaint, and may exert a profound negative impact on the man's life and partnership. Using currently available treatment alternatives (e.g., selective serotonin uptake inhibitor, agents acting locally on the penis), PE can be treated in most, but not all patients. However, since long term success rates have been disappointing, and the only approved treatment so far is the short-acting selective serotonin re-uptake inhibitor dapoxetine, there is currently an intensive search for new treatment modalities. Selection of the most promising therapeutic targets from a host of current and potential candidates depends heavily on their roles in the pathophysiology of PE. Possible central nervous targets that will be discussed are serotonin transporters, and CNS receptors for 5-HT(IA) and 5-HT(1B), dopamine, oxytocin, opioids, neurokinin-1, and glutamate. Putative peripheral targets include ?(1)-adrenoceptors, phosphodiestrase enzymes, Rho kinases, purinergic (P2X) receptors, and penile sensory nerves. It is clear that exploiting the full therapeutic potential of these targets will require additional basic and clinical research. PMID:21816550

  20. Keeping Your Head On Target

    PubMed Central

    Wong, Aaron L.; Zee, David S.; Jinnah, H. A.

    2013-01-01

    The mechanisms by which the human brain controls eye movements are reasonably well understood, but those for the head less so. Here, we show that the mechanisms for keeping the head aimed at a stationary target follow strategies similar to those for holding the eyes steady on stationary targets. Specifically, we applied the neural integrator hypothesis that originally was developed for holding the eyes still in eccentric gaze positions to describe how the head is held still when turned toward an eccentric target. We found that normal humans make head movements consistent with the neural integrator hypothesis, except that additional sensory feedback is needed, from proprioceptors in the neck, to keep the head on target. We also show that the complicated patterns of head movements in patients with cervical dystonia can be predicted by deficits in a neural integrator for head motor control. These results support ideas originally developed from animal studies that suggest fundamental similarities between oculomotor and cephalomotor control, as well as a conceptual framework for cervical dystonia that departs considerably from current clinical views. PMID:23825431