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  1. 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 ...

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

    ClinicalTrials.gov

    2016-04-19

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

  3. What Causes Thrombotic Thrombocytopenic Purpura?

    MedlinePlus

    ... and Marrow Stem Cell Transplant Excessive Blood Clotting Hemolytic Anemia Send a link to NHLBI to someone by ... the body can replace them. This leads to hemolytic anemia . Inherited Thrombotic Thrombocytopenic Purpura In inherited TTP, the ...

  4. Idiopathic thrombocytopenic purpura

    PubMed Central

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

    2014-01-01

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

  5. Thrombotic thrombocytopenic purpura preceding systemic lupus erythematosus.

    PubMed Central

    Simeon-Aznar, C P; Cuenca-Luque, R; Fonollosa-Pla, V; Bosch-Gil, J A

    1992-01-01

    The case of a patient admitted with thrombotic thrombocytopenic purpura nine years after developing systemic lupus erythematosus (SLE) is reported. Thrombotic thrombocytopenic purpura associated with SLE has been described on other occasions, but in most patients the diagnosis of SLE precedes that of thrombotic thrombocytopenic purpura. The unusual sequence and the chronological separation of the two diseases is emphasised. PMID:1575591

  6. 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

  7. 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...

  8. 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

  9. Thrombotic thrombocytopenic purpura after a dogbite.

    PubMed

    Mars, D R; Knochel, J P; Cotton, J R; Fuller, T J

    1980-05-01

    A man bitten by a pet dog had fulminant thrombotic thrombocytopenic purpura within 72 hours. Rhabdomyolysis was severe and acute anuric renal failure was present. The suspected causative agent was Pastuerella multocida or clostridia with possible endotoxemia, though early treatment precluded a definitive diagnosis. The patient responded dramatically to a combined therapeutic approach of antibiotics, steroids, splenectomy, and supportive hemodialysis. PMID:7189607

  10. 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

  11. 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

  12. [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

  13. Thrombotic thrombocytopenic purpura in southeastern New England.

    PubMed

    Crowley, J P; Zaroulis, C G; O'Shea, P A; Clark, D D

    1983-05-01

    Eight patients with thrombotic thrombocytopenic purpura (TTP) originating within a 25-mile radius had their conditions diagnosed in a three-year period at a community teaching hospital in southeastern New England. In the preceding ten years, only one case of TTP had occurred in the same hospital. A niece-uncle relationship was present in two patients, and lymphocyte typing showed that they both shared an HLA haplotype. In the remaining patients, no social, familial, or environmental connection was established. Three patients died, all of whom were female. Six patients received exchange plasmapheresis with excellent responses in five. Autopsies in the three fatal cases showed widespread organ involvement with TTP but did not disclose evidence of any common underlying disease. This unusual occurrence should alert physicians to the possibility of localized outbreaks of TTP and the necessity of considering this diagnosis in all patients with unexplained thrombocytopenia. PMID:6383244

  14. [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

  15. 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 ...

  16. Bone marrow examination before steroids in thrombocytopenic purpura or arthritis.

    PubMed

    Reid, M M

    1992-12-01

    Corticosteroids were used to treat two children with presumed idiopathic thrombocytopenic purpura and one with juvenile rheumatoid arthritis without examination of the bone marrow. Of the two with presumed idiopathic thrombocytopenic purpura, one had Fanconi's anaemia and the other may have had aplastic anaemia. The third child had acute lymphoblastic leukaemia. The diagnosis of Fanconi's anaemia was delayed. A diagnostic and therapeutic dilemma was caused in the second case. In the third, delayed diagnosis and, perhaps, compromised outlook resulted. These three cases re-emphasize the well aired caveats about the diagnosis of idiopathic thrombocytopenic purpura and juvenile rheumatoid arthritis and provide further support for the arguments of those who believe that if corticosteroids are to be used to treat such children, their bone marrow should be examined first. PMID:1290852

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Immune thrombocytopenic purpura in a child with acute lymphoblastic leukemia and mumps.

    PubMed

    Kurekci, A Emin; Atay, A Avni; Demirkaya, Erkan; Sarici, S Umit; Ozcan, Okan

    2006-03-01

    Immune thrombocytopenic purpura in childhood is characterized by a typical history of acute development of purpura and bruising in an otherwise healthy child. In children it usually follows a viral infection (eg, mumps, rubella) or immunization. We report for the first time a child with acute lymphoblastic leukemia who developed immune thrombocytopenic purpura due to mumps during the maintenance phase of acute lymphoblastic leukemia treatment. PMID:16679943

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura

    PubMed Central

    2008-01-01

    Discoveries during the past decade have revolutionized our understanding of idiopathic thrombotic thrombocytopenic purpura (TTP). Most cases in adults are caused by acquired autoantibodies that inhibit ADAMTS13, a metalloprotease that cleaves von Willebrand factor within nascent platelet-rich thrombi to prevent hemolysis, thrombocytopenia, and tissue infarction. Although approximately 80% of patients respond to plasma exchange, which removes autoantibody and replenishes ADAMTS13, one third to one half of survivors develop refractory or relapsing disease. Intensive immunosuppressive therapy with rituximab appears to be effective as salvage therapy, and ongoing clinical trials should determine whether adjuvant rituximab with plasma exchange also is beneficial at first diagnosis. A major unanswered question is whether plasma exchange is effective for the subset of patients with idiopathic TTP who do not have severe ADAMTS13 deficiency. PMID:18574040

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Harmful and beneficial antibodies in immune thrombocytopenic purpura.

    PubMed Central

    Imbach, P A

    1994-01-01

    Two facts support the definition of idiopathic thrombocytopenic purpura (ITP) as an immune disorder. First, antibodies against platelets, which often appear after a viral infection, provoke the increased elimination of these cells. Viral disease may change the complex immune response of the host at different levels. In chronic ITP, the consequences of the dysregulated immune system are autoantibodies, primarily against platelet glycoprotein IIb/IIIa. Second, pooled immunoglobulins from healthy blood donors may influence the imbalanced immune response in ITP. The initial study dose of 5 x 0.4 g of intact 7S IgG/kg body weight can now be reduced to 2 x 0.4 g/kg body weight in the majority of patients. The possible mechanisms of action of intravenous immune globulin (IVIG) are reviewed and updated in this article. The combination of effects on the humoral and cellular immune responses using IVIG in concert with cytokines may open up new therapeutic possibilities. PMID:8033430

  15. 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.

  16. 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

  17. Pregnancy and Birth Outcomes among Women with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Wyszynski, Diego F.; Carman, Wendy J.; Cantor, Alan B.; Graham, John M.; Kunz, Liza H.; Slavotinek, Anne M.; Kirby, Russell S.; Seeger, John

    2016-01-01

    Objective. To examine pregnancy and birth outcomes among women with idiopathic thrombocytopenic purpura (ITP) or chronic ITP (cITP) diagnosed before or during pregnancy. Methods. A linkage of mothers and babies within a large US health insurance database that combines enrollment data, pharmacy claims, and medical claims was carried out to identify pregnancies in women with ITP or cITP. Outcomes included preterm birth, elective and spontaneous loss, and major congenital anomalies. Results. Results suggest that women diagnosed with ITP or cITP prior to their estimated date of conception may be at higher risk for stillbirth, fetal loss, and premature delivery. Among 446 pregnancies in women with ITP, 346 resulted in live births. Women with cITP experienced more adverse outcomes than those with a pregnancy-related diagnosis of ITP. Although 7.8% of all live births had major congenital anomalies, the majority were isolated heart defects. Among deliveries in women with cITP, 15.2% of live births were preterm. Conclusions. The results of this study provide further evidence that cause and duration of maternal ITP are important determinants of the outcomes of pregnancy. PMID:27092275

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. [A Case of Esophageal Cancer Complicated with Idiopathic Thrombocytopenic Purpura].

    PubMed

    Nakahara, Yujiro; Yamasaki, Makoto; Makino, Tomoki; Miyazaki, Yasuhiro; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2015-11-01

    The patient was a 58-year-old woman. She was diagnosed with idiopathic thrombocytopenic purpura (ITP) when she was 41 years old. Splenectomy was performed at age 55; however, there was no response (NR). Therapy with prednisolone was continued. She underwent endoscopic examination because of dysphagia, and an esophageal tumor was revealed. She was diagnosed with esophageal squamous cell carcinoma (Mt, cT3N1M0, Stage ⅢA). She received high-dose g-globulin therapy and platelet transfusion before surgery, and the platelet count subsequently increased to 11.0×10(4) mm3. A subtotal esophagectomy was performed. The platelet count was low immediately after surgery; however, it increased after POD5. The patient was discharged without complications. She is alive without recurrence 9 years after surgery. This is the first report of esophageal cancer complicated with ITP that was not responsive to splenectomy. We report this case along with a discussion. PMID:26805214

  4. Pregnancy and Birth Outcomes among Women with Idiopathic Thrombocytopenic Purpura.

    PubMed

    Wyszynski, Diego F; Carman, Wendy J; Cantor, Alan B; Graham, John M; Kunz, Liza H; Slavotinek, Anne M; Kirby, Russell S; Seeger, John

    2016-01-01

    Objective. To examine pregnancy and birth outcomes among women with idiopathic thrombocytopenic purpura (ITP) or chronic ITP (cITP) diagnosed before or during pregnancy. Methods. A linkage of mothers and babies within a large US health insurance database that combines enrollment data, pharmacy claims, and medical claims was carried out to identify pregnancies in women with ITP or cITP. Outcomes included preterm birth, elective and spontaneous loss, and major congenital anomalies. Results. Results suggest that women diagnosed with ITP or cITP prior to their estimated date of conception may be at higher risk for stillbirth, fetal loss, and premature delivery. Among 446 pregnancies in women with ITP, 346 resulted in live births. Women with cITP experienced more adverse outcomes than those with a pregnancy-related diagnosis of ITP. Although 7.8% of all live births had major congenital anomalies, the majority were isolated heart defects. Among deliveries in women with cITP, 15.2% of live births were preterm. Conclusions. The results of this study provide further evidence that cause and duration of maternal ITP are important determinants of the outcomes of pregnancy. PMID:27092275

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

    PubMed

    Coppo, Paul; Froissart, Antoine

    2015-01-01

    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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. High procalcitonin and thrombocytopenic purpura in a case of Kikuchi-Fujimoto disease.

    PubMed

    de Luca, A; Parizel, A; Fromont, G; Roblot, P; Roblot, F; Gambert-Abdel Rahman, C; Hankard, R

    2015-06-01

    Kikuchi-Fujimoto disease is a mild and rare idiopathic disease, particularly in children. It is mostly characterized by painful cervical lymphadenopathy and/or prolonged fever and confirmed by histology. We report a case of Kikuchi-Fujimoto disease in a 14-year-old teenager with high procalcitonin concentration and thrombocytopenic purpura. PMID:23769629

  12. Low serum levels of interleukin-6 in children with post-infective acute thrombocytopenic purpura.

    PubMed

    Gangarossa, S; Romano, V; Munda, S E; Sciotto, A; Schilirò, G

    1995-08-01

    Interleukin-6 plays an important role in host defense mechanisms and it appears to be a major mediator of the acute-phase response. IL-6 is also an important thrombocytopoietic factor. High serum levels of IL-6 are present in reactive thrombocytosis. The number and function of circulating platelets are the major factors that affect megakaryocytopoiesis by thrombopoietin. High levels of thrombopoietin have been observed in patients with thrombocytopenic purpura. To evaluate a possible thrombopoietin-like function of IL-6, we measured IL-6 levels in the serum of patients affected by post-infective acute thrombocytopenic purpura using a sensitive ELISSA assay. As controls, we studied normal subjects and patients with reactive thrombocytosis. No significant difference was observed between thrombocytopenic patients and normal controls. High IL-6 levels were present in patients with reactive thrombocytosis. In conclusion, we had not observed high levels of IL-6 in acute thrombocytopenic purpura and, very probably, IL-6 is not involved in the regulation of platelet mass for the hemostatic function. The thrombocytopoietic activity of IL-6 is another acute-phase response and it is consistent with the other functions of this cytokine. This suggests an active participation of platelets in host defense mechanisms. PMID:7628586

  13. 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/μL. 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

  14. 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

  15. 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

  16. Newly diagnosed immune thrombocytopenic purpura in childhood: successful implementation of a limited intervention strategy in the setting of pediatric emergency care.

    PubMed

    Rohmer, Barbara; Valla, Frédéric V; Baleydier, Frédéric; Launay, Valérie; Dommange-Romero, Florence; Pondarré, Corinne

    2015-02-01

    Immune thrombocytopenic purpura is a bleeding disorder for which management remains mainly guided by platelet counts. Pediatric hematologists and emergency physicians collaborated to set up a limited intervention strategy, focusing on clinical bleeding severity irrespective of platelet counts, starting in the emergency room. We report how this strategy was safely applied for 106 consecutive children admitted for newly diagnosed immune thrombocytopenic purpura. PMID:25454932

  17. 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

  18. [Variety of thrombotic thrombocytopenic purpura clinical course in Polish family members with ADAMTS 13 gene mutation].

    PubMed

    Hyla-Klekot, Lidia; Kucharska, Grazyna; Słonka, Karina

    2013-03-01

    The congenital form of thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrom) is a result of genetically conditioned dysfunction of protease ADAMTS 13 enzyme which is responsible for von Wiellebrand factor multimer disintegration. The disease is inherited autosomally and recessively. The decrease of ADAMTS 13 activity results in intravascular clotting process activation with rapid lowering of platelet count, haemolytic anaemia, and occurence of schistocytes. Clinically, the disease is characterized by a range of symptoms such as severe jaundice in neonatal period, embolicthrombotic incidents of nervous system and progressive dysfunction of kidneys and other organs. Delaying diagnosis and hence administering of freshly frozen plasma leads to death. Molecular diagnosis allows for identification of genetical profile of the patient, and showing lowered enzyme activity is a basis for regular prophylactic plasma administration which is the protease donor. In our study we present members of a Polish family identified with ADAMTS 13 mutation. 52 old male with heterozygotic mutation of exon 29 (4143_4144insA) and in exon 19 (c2281G>A; Gly761Ser), experienced a few episodes of ischaemic stroke with ongoing neurological deficiency and developed chronic kidney disease. His 16-year old daughter with double homozygotic mutation in exon 29 (4143_4144insA) after severe episode of TTP at the age of 4 has been receiving plasma every 2 weeks for 12 years, which prevented her from other disorders. Target treatment introduced to clinical practice by means of ADAMTS 13 obtained by genetic recombination technology raises hopes. PMID:23700827

  19. [The dynamic detection of cytokins under aplastic anemia and idiopathic thrombocytopenic purpura in the process of impact of hypoxic hypoxia].

    PubMed

    Éralieva, M O

    2012-05-01

    The natural hypoxic hypoxia enhances the synthesis processes and decrease the concentration balance in cytokine rets in patients with depression of hematopoiesis. It is established that the patients with aplastic anemia and idiopathic thrombocytopenic purpura, in contrast with patients with acute leucosis, chronic myelolecosis and erythroid myeloma, have quite high values of IL-2, which can be involved in the organization of full-fledgee response to antigen stimuli. The application of hypoxic hypoxia as an additional method in treatment of aplastic anemia and idiopathic thrombocytopenic purpura has no side effects and contraindications. PMID:22834158

  20. 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

  1. 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.

  2. 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

  3. Controversies in the diagnosis and management of childhood acute immune thrombocytopenic purpura.

    PubMed

    Segel, George B; Feig, Stephen A

    2009-09-01

    Acute immune thrombocytopenic purpura (ITP) occurs most commonly in young children who present with severe isolated thrombocytopenia and purpura. A marrow examination is not required unless glucocorticoids are used, lest treatment mask incipient acute lymphoblastic leukemia, but controversy exists here. The recommendations for evaluation and management remain controversial, since prospective controlled trials have not been done. There is some consensus based on experience and empiric data. Almost all children with acute ITP will recover completely without therapy. Although the various treatments may increase the platelet count, they do not influence the outcome of the illness, may increase cost, and cause significant side effects. Therefore, careful observation may be the best management option for the patient with ITP, in the absence of severe bleeding. The data available relevant to these issues are discussed. PMID:19165890

  4. 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

  5. Focal ulcerative ileocolitis with terminal thrombocytopenic purpura in juvenile cotton top tamarins (Saguinus oedipus).

    PubMed

    Snook, S S; Canfield, D R; Sehgal, P K; King, N W

    1989-03-01

    A newly recognized syndrome characterized by an acute focal ulcerative ileocolitis, anemia and thrombocytopenic purpura in five juvenile cotton-top tamarins is described. The presentation and morphology of this syndrome is distinct from any other reported gastrointestinal disease reported in tamarins. Traditional etiologies such as viruses, ingested toxins, Campylobacter, Salmonella and Yersinia and Clostridium difficile are not considered likely etiologic agents. Nontraditional etiologies such as anaerobes or pathologic strains of Escherichia coli are now being considered. This syndrome is of potential significance to ongoing research into the etiology of idiopathic tamarin colitis. PMID:2496272

  6. 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.

  7. 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

  8. 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

  9. Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient.

    PubMed

    Lugao, Renata dos Santos; Motta, Marina Pamponet; de Azevedo, Matheus Freitas Cardoso; de Lima, Roque Gabriel Rezende; Abrantes, Flávia de Azevedo; Abdala, Edson; Carrilho, Flair José; Mazo, Daniel Ferraz de Campos

    2014-07-01

    A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura (ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack of tuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas. PMID:25009408

  10. 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

  11. Clopidogrel-induced refractory thrombotic thrombocytopenic purpura successfully treated with rituximab.

    PubMed

    Khodor, Sara; Castro, Miguel; McNamara, Colin; Chaulagain, Chakra P

    2016-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by microvascular aggregation of platelets and fibrin strands causing thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction. TTP can develop as a result of a deficiency in ADAMTS13 enzyme activity due to either a genetic defect or, more commonly, the development of anti-ADAMTS13 autoantibodies. TTP can also be associated with pregnancy, organ transplant, lupus, infections, and drugs. Here, we present a case of TTP that developed shortly after the start of clopidogrel treatment for acute ischemic stroke and acute myocardial infarction, and describe the clinical presentation, refractory course of the disease, and successful induction of remission through the use of rituximab in a setting of pre-existing autoimmune diseases. PMID:26684918

  12. 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

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

    PubMed

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

    2009-11-01

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

  14. Using decision analysis techniques to deal with "unanswerable" questions in idiopathic thrombocytopenic purpura.

    PubMed

    Klaassen, Robert

    2003-12-01

    Idiopathic thrombocytopenic purpura (ITP) is a common disorder with rare adverse outcomes. This makes it a particularly difficult area in which to undertake conventional studies. An alternative method for solving clinical questions is decision analysis, which is in essence a computer-assisted synthesis of the literature. Using the example of a newly diagnosed ITP patient, the author attempts to answer the question of whether a bone marrow aspirate (BMA) is required prior to starting steroids. Using decision analysis methodology, the author determines that BMA is not essential prior to starting steroids. More importantly, three variables critical to the decision-making process are determined: the risk of death from the BMA procedure, the altered chance of survival for a patient with acute lymphoblastic leukemia (ALL) inappropriately given steroids, and how sensitive the complete blood count is at determining the risk of ALL. This scenario demonstrates the value of decision analysis and lays the groundwork for future endeavors. PMID:14668643

  15. 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

  16. Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient

    PubMed Central

    Lugao, Renata dos Santos; Motta, Marina Pamponet; de Azevedo, Matheus Freitas Cardoso; de Lima, Roque Gabriel Rezende; Abrantes, Flávia de Azevedo; Abdala, Edson; Carrilho, Flair José; Mazo, Daniel Ferraz de Campos

    2014-01-01

    A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura (ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack of tuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas. PMID:25009408

  17. [A Case of Idiopathic Thrombocytopenic Purpura during Adjuvant Chemotherapy for Colon Cancer].

    PubMed

    Takahara, Yoshihiro; Ozawa, Shinichi; Ogasawara, Takeshi; Shida, Takashi; Nomura, Satoru; Sato, Yoshiharu; Takahashi, Makoto

    2015-11-01

    A 76-year-old man underwent surgery for sigmoid colon cancer. The pathological finding was stage Ⅱ with a high-risk of recurrence (SI [bladder], l y0, v2, pN0, H0, P0, M0). He was treated with TS-1 as adjuvant chemotherapy. After the 1 course of chemotherapy, his platelet count was 4,000/mL. The high index of platelet associated IgG (PA-IgG) and bone marrow examination suggested that thrombocytopenia was caused by idiopathic thrombocytopenic purpura. The platelet count improved by prednisolone administration and Helicobacter pylori eradication treatment. After 6 months with no administration of adjuvant chemotherapy, the colon cancer recurred locally, and we performed a Hartmann's operation. PMID:26805292

  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. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Elevated common acute lymphoblastic leukemia antigen expression in pediatric immune thrombocytopenic purpura.

    PubMed

    Cornelius, A S; Campbell, D; Schwartz, E; Poncz, M

    1991-01-01

    Bone marrow examination is often performed in thrombocytopenic children to distinguish immune thrombocytopenic purpura (ITP) from acute leukemia. We describe a patient with thrombocytopenia and 50% common acute lymphoblastic leukemia antigen (CALLA) positivity in his marrow who was subsequently shown to have ITP. CALLA (CD10) is a surface antigen found in early B-lymphocytes and is elevated in most cases of childhood acute lymphoblastic leukemia (ALL). This case prompted us to prospectively study the frequency of immature lymphocyte populations in children with ITP. Fourteen patients with acute ITP and five with other conditions were studied. The two groups were comparable with respect to age: ITP mean, 4.3 (range 0.3-15.5) years; control mean, 5.8 (0.6-13.8) years. The ITP group had a significantly higher percentage of CD10 positive bone marrow lymphocytes (p = 0.007). Five of the 10 patients younger than 4 years of age in the ITP group had CD10 levels of greater than 30%, which is in the leukemic range, whereas none of the control patients had a CD10 levels of greater than 17% (p = 0.003). There was good correlation between CD10 positivity and B4 positivity indicating that both of these markers arise from the same population of immature B-lymphocytes. None of the ITP patients who were older than 4 years had a CD10 level of greater than 30%. We conclude that it is common to have an increase in the proportion of immature lymphocytes in the marrow of young children with ITP. The cause of this increase in CD10 positive cells is unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1827572

  6. 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

  7. 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

  8. Acquired thrombotic thrombocytopenic purpura after vascular prosthesis implantation for impending rupture of an abdominal aortic aneurysm.

    PubMed

    Naito, Chiaki; Ogawa, Yoshiyuki; Yanagisawa, Kunio; Ishizaki, Takuma; Mihara, Masahiro; Handa, Hiroshi; Isonishi, Ayami; Hayakawa, Masaki; Matsumoto, Masanori; Nojima, Yoshihisa

    2016-01-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13. TTP patients run a rapidly fatal course unless immediate plasma exchange (PEX) is initiated upon diagnosis. Herein, we report a 72-year-old man with TTP, which developed after he underwent artificial blood vessel replacement surgery for an abdominal aneurysm with impending rupture. In the perioperative period, the patient received several platelet transfusions for severe thrombocytopenia (minimum platelet count: 0.6×10(4)/μl). Thereafter, he was admitted to our department for rapidly progressing coma with multiple cerebral infarctions, and was transferred to the ICU. Based on the tentative diagnosis of TTP, we immediately began PEX and steroid pulse therapy. The diagnosis was confirmed thereafter by markedly reduced ADAMTS13 activity (<0.5%) and his being positive for the ADAMTS13 inhibitor. We performed PEX for five consecutive days and administered high-dose prednisolone (PSL). On the second hospital day (HD), his platelet count rose along with improvement of his consciousness level. The ADAMTS13 inhibitor was not detected on the 10th HD. TTP did not relapse and his general condition improved despite tapering of PSL. In this case, by closely monitoring ADAMTS13-related parameters and minimizing the number of plasma exchanges, the patient was able to achieve a remission without the use of boosting inhibitors. PMID:27076251

  9. [Accessory spleens--diagnostic and therapeutic problem of the laparoscopic splenectomy in idiopathic thrombocytopenic purpura patients].

    PubMed

    Stanek, A; Makarewicz, W; Stefaniak, T; Kaska, L; Podgórczyk, H; Hellman, A

    2004-04-01

    The preoperative detection of accessory spleens (AS) is essential in ITP patients. The aim of this study was to evaluate the reasons of failure and long-term results of laparoscopic splenectomy (LS) in patients with idiopathic thrombocytopenic purpura (ITP). Thirty-four ITP patients (27 females and 7 males) underwent LS between June 1998 and January 2001. Computed Tomography (CT) and sonography (US) were performed preoperatively to evaluate the size of the spleen and to detect the presence of possible accessory spleens which were found in two cases. AS were seen during laparoscopy in three cases. During follow-up (median time = 23 months), in three patients a low platelet count was seen after 5 months, 1.5 and 1.8 years pop. In all these cases scintigraphy was performed, which revealed in one case the residual accessory spleen. In the two other patients, inspite of thrombocytopenia no residual spleens were found. The authors conclude that laparoscopic splenectomy is a safe and effective procedure in patients with ITP. The problem of accessory spleens can be managed by careful videoscopic examination of the abdominal cavity during splenectomy. The use of the preoperative imaging techniques for detection of accessory spleens is limited by the insufficient sensitivity of the examination. PMID:15106042

  10. 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

  11. 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

  12. Life-Threatening Autoimmune Hemolytic Anemia and Idhiopatic Thrombocytopenic Purpura. Successful Selective Splenic Artery Embolization

    PubMed Central

    Molica, Matteo; Massaro, Fulvio; Annechini, Giorgia; Baldacci, Erminia; D’Elia, Gianna Maria; Rosati, Riccardo; Trisolini, Silvia Maria; Volpicelli, Paola; Foà, Robin; Capria, Saveria

    2016-01-01

    Selective splenic artery embolization (SSAE) is a nonsurgical intervention characterized by the transcatheter occlusion of the splenic artery and/or its branch vessels using metallic coils or other embolic devices. It has been applied for the management of splenic trauma, hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia and splenic hemangioma. We hereby describe a case of a patient affected by idiopathic thrombocytopenic purpura (ITP) and warm auto-immune hemolytic anemia (AIHA) both resistant to immunosuppressive and biological therapies, not eligible for a surgical intervention because of her critical conditions. She underwent SSAE and achieved a hematologic complete response within a few days without complications. SSAE is a minimally invasive procedure to date not considered a standard option in the management of AIHA and ITP. However, following the progressive improvement of the techniques, its indications have been extended, with a reduction in morbidity and mortality compared to splenectomy in patients with critical clinical conditions. SSAE was a lifesaving therapeutic approach for our patient and it may represent a real alternative for the treatment of resistant AIHA and ITP patients not eligible for splenectomy. PMID:27158433

  13. Combination immunosuppressant therapy for patients with chronic refractory immune thrombocytopenic purpura.

    PubMed

    Arnold, Donald M; Nazi, Ishac; Santos, Aurelio; Chan, Howard; Heddle, Nancy M; Warkentin, Theodore E; Kelton, John G

    2010-01-01

    Treatment options for patients with chronic refractory immune thrombocytopenic purpura (ITP) are limited. Because combination immunosuppressant therapy appeared to be effective in ITP and other disorders, we used this approach in patients with particularly severe and refractory ITP. In this retrospective, observational study, we determined the response (platelet count above 30 x 10(9)/L and doubling of baseline) among 19 refractory ITP patients. Treatment consisted of azathioprine, mycophenolate mofetil, and cyclosporine. The patients had failed a median of 6 prior treatments, including splenectomy (in all except 1). Of 19 patients, 14 (73.7%) achieved a response lasting a median of 24 months, after which time 8 (57.1%) relapsed. Of the 8 relapsing patients, 6 responded to additional treatments. Of the 14 patients who achieved an initial response, 2 (14.3%) remained in remission after eventually stopping all medications. Severe adverse events did not occur. Combination immunosuppressant therapy can produce a rise in the platelet count that is sometimes sustained in refractory ITP patients. PMID:19897578

  14. Treatment of acute idiopathic thrombocytopenic purpura (AITP): cooperative Italian study group results.

    PubMed

    Mori, P G; Lanza, T; Mancuso, G; De Mattia, D; Catera, P; Miano, C; Del Principe, D; Cottafava, F

    1988-01-01

    A cooperative Italian study group on acute idiopathic thrombocytopenic purpura (AITP) has been designed to evaluate efficacy and safety of no treatment at the onset of the disease and sequential treatment with immunoglobulin and high dose steroid. One hundred thirty-eight patients with AITP entered in the trial. Eleven patients were treated before the end of the waiting period because of bleeding. One hundred twenty-seven (92%) received no treatment for the first 10 days of the disease, 65 patients (51.18%) recovered spontaneously, 62 patients were treated with immunoglobulin, and 52 (83.8%) of them responded positively but only 36 (58.06%) permanently. There was no statistical difference between the results obtained with 400 mg/kg for 5 days versus 200 mg/kg. Twenty-four patients were treated with high doses of steroids, 20 (83.3%) with positive response, and 10 (41.66%) were permanently cured. Four (3.14%) of the patients enrolled in the protocol still had active disease at the end of treatment, and 10 relapsed within 4 months after the end of the treatment. PMID:3155240

  15. ADAMTS13 phenotype in plasma from normal individuals and patients with thrombotic thrombocytopenic purpura

    PubMed Central

    Manea, Minola; Kristoffersson, AnnCharlotte; Tsai, Han-Mou; Zhou, Wenhua; Winqvist, Ingemar; Oldaeus, Göran; Billström, Rolf; Björk, Peter; Holmberg, Lars

    2006-01-01

    The activity of ADAMTS13, the von Willebrand factor cleaving protease, is deficient in patients with thrombotic thrombocytopenic purpura (TTP). In the present study, the phenotype of ADAMTS13 in TTP and in normal plasma was demonstrated by immunoblotting. Normal plasma (n = 20) revealed a single band at 190 kD under reducing conditions using a polyclonal antibody, and a single band at 150 kD under non-reducing conditions using a monoclonal antibody. ADAMTS13 was not detected in the plasma from patients with congenital TTP (n = 5) by either antibody, whereas patients with acquired TTP (n = 2) presented the normal phenotype. Following immunoadsorption of immunoglobulins, the ADAMTS13 band was removed from the plasma of the patients with acquired TTP, but not from that of normal individuals. This indicates that ADAMTS13 is complexed with immunoglobulin in these patients. The lack of ADAMTS13 expression in the plasma from patients with hereditary TTP may indicate defective synthesis, impaired cellular secretion, or enhanced degradation in the circulation. This study differentiated between normal and TTP plasma, as well as between congenital and acquired TTP. This method may, therefore, be used as a complement in the diagnosis of TTP. PMID:17187257

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

    PubMed

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

    2009-03-01

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

  17. A proposal: the need for thrombotic thrombocytopenic purpura Specialist Centres--providing better outcomes.

    PubMed

    Dutt, Tina; Scully, Marie

    2015-09-01

    Thrombotic thrombocytopenic purpura (TTP) is heralded by its demanding presentation and impending mortality. The complex and life-threatening characteristics of TTP justify the need for early referral and responsive management in centres with comprehensive multi-disciplinary resources. In an era where compromise of patient safety or experience is unsatisfactory, the provision of specialist-led, organized care for this patient group remains overdue. Patients and clinical teams continue to lack the knowledge, support and resources required to achieve consistently high levels of clinical care. This forms the rationale for development of TTP Specialist Centres. In this article we focus on what we believe to be the recognized and potential merits of a specialist service provision, highlighting individual components of a high level of integrated expertise. The challenges in managing the condition from acute diagnosis to long-term care are described alongside defining key standards that represent excellence in patient care. The emphasis will be on understanding how the evolution of TTP Specialist Centres diverges from an ad hoc approach to managing this vulnerable patient group and offers promise in the translation to improved patient outcomes. PMID:26104507

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

    PubMed

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

    2014-01-01

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

  19. 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

  20. Impact of Helicobacter pylori Eradication Therapy on Platelet Counts in Patients With Chronic Idiopathic Thrombocytopenic Purpura.

    PubMed

    Amiri, Mohamadreza

    2016-01-01

    This study was a before and after clinical evaluation of Helicobacter pylori eradication on platelet counts in a group of 23 patients with chronic Idiopathic (Autoimmune) thrombocytopenic purpura (CITP). H. pylori infection was identified in patients by a 13C-urea breath test and confirmed by an H. pylori stool antigen test. Eradication was conducted in patients testing positive. Infected (n = 10) and uninfected (n = 13) patient groups did not differ with respect to age, gender, history of previous splenectomy, treatment with anti-D, current treatment with corticosteroids, or initial platelet counts. H pylori eradication was successful in eight infected CITP patients, with two patients not responsive to treatment. Compared to the uninfected group, patients in the infected group who responded to eradication therapy had significantly increased platelet counts after six months (56.2 ± 22.2 vs. 233 ± 85.6 ×103 million cells/L; P < 0.01), whereas platelet counts in the non-responding patients and uninfected group did not differ after this period of time. H. pylori eradication promotes significant platelet count improvement in patients with CITP. Thus, all patients with CITP should be tested and treated for H. pylori infections. PMID:26925898

  1. 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.

  2. 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

  3. 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.

  4. [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

  5. 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

  6. Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature.

    PubMed

    Huenerberg, Katherine; Hudspeth, Michelle; Bergmann, Shayla; Pai, Shashidhar; Singh, Balvir; Duong, Angie

    2016-05-01

    Vici syndrome is a rare congenital disorder first described in 1988. To date, 31 cases have been reported in the literature. The characteristic features of this syndrome include: agenesis of the corpus callosum, albinism, cardiomyopathy, variable immunodeficiency, cataracts, and myopathy. We report two Hispanic sisters with genetically confirmed Vici syndrome who both developed Idiopathic Thrombocytopenic Purpura. To our knowledge, this is an immunologic process that has been previously undescribed within the phenotype of Vici syndrome and should be added to the spectrum of variable immune dysregulation that can be found in these patients. © 2016 Wiley Periodicals, Inc. PMID:26854214

  7. Lessons learned from the Oklahoma thrombotic thrombocytopenic purpura-hemolytic uremic syndrome registry.

    PubMed

    George, James N; Terrell, Deirdra R; Swisher, Karen K; Vesely, Sara K

    2008-01-01

    The Oklahoma TTP-HUS Registry provides a complete community perspective of thrombotic thrombocytopenic purpura (TTP). This is possible because plasma exchange is the essential treatment for TTP and the Oklahoma Blood Institute provides all plasma exchange procedures for a region encompassing most of the State, including 58 of Oklahoma's 77 counties. The Registry is an inception cohort of consecutive patients for whom plasma exchange treatment was requested for a diagnosis of either TTP or hemolytic uremic syndrome (HUS). All 382 patients identified from January 1, 1989 to December 31, 2007 have consented to be enrolled. Complete follow-up is available for 380 of 382 patients. Patients are described both by clinical categories, related to their associated conditions and clinically apparent etiologies, and by the presence of severe ADAMTS13 deficiency. ADAMTS13 activity has been measured on 235 (93%) of 254 patients since 1995. Registry data have provided new perspectives on the definition and diagnoses of these syndromes as well as their outcomes. Long-term follow-up has documented that relapse is common among patients with ADAMTS13 deficiency but rarely occurs in patients without ADAMTS13 deficiency. Long-term follow-up has also documented persistent abnormalities of health-related quality-of-life and cognitive function. In addition to providing new perspectives on the natural history of these syndromes, The Oklahoma TTP-HUS Registry provides a support group for our patients, information about evaluation and management for community physicians, and a resource for research and educational programs. PMID:18618590

  8. Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

    PubMed

    Ay, Yilmaz; Karapinar, Tuba H; Oymak, Yesim; Toret, Ersin; Demirag, Bengu; Ince, Dilek; Ozcan, Esin; Moueminoglou, Nergial; Koker, Sultan A; Vergin, Canan

    2016-06-01

    Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab. PMID:26656905

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

    PubMed

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

    2015-08-01

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

  10. Phenotypic analysis of bone marrow lymphocytes from children with acute thrombocytopenic purpura.

    PubMed

    Guiziry, Dalai E L; El, Gendy Wessam; Farahat, Nahla; Hassab, Hoda

    2005-01-01

    Hematogones are benign immature B cells that commonly populate the bone marrow of children. Their presence has been noted to interfere with the flow-cytometric analysis of acute lymphoblastic leukemia (ALL), because their immunophenotype is similar to B-precursor cell lymphoblasts. Immune-mediated thrombocytopenia is a clinical condition characterized by increased platelet destruction due to sensitization of platelets by autoantibodies. The aim of this study was to determine the incidence and clinical impact of bone marrow hematogones in cases of acute immune thrombocytopenic purpura (ITP) among children. This was done by immunophenotyping of bone marrow lymphocytes of ITP cases and controls and follow up of cases. This study was done on 25 cases of ITP, 12 females and 13 males, their age ranged from 2 to 13 years. A control group was included in the study, 15 cases of apparently healthy children with matching age and sex taken from among bone marrow donors. Cases and controls were subjected to bone marrow lymphocyte immunophenotyping with flow-cytometry to verify the presence of hematogones. A statistically significant increase in the percentage of hematogones was demonstrated in their bone marrows. An increased percentage of CD10+ lymphocytes was demonstrated; with a mean of 18+/-15.2%, CD19+ with a mean of 27+/-16.3% and CD34+ with a mean of 3.7+/-3.2%. No correlation was found between the percentage of hematogones and peripheral platelet count or bone marrow lymphocytic count. In conclusion, there is an increase in the bone marrow hematogones in ITP cases in comparison to normal controls. This could be the sequence of an immunological response to the cause which determined the disease, or the regeneration of the stem cell compartment following transient damage. PMID:16734134

  11. BONE MARROW NECROSIS DISCOVERED IN A PATIENT WITH SUSPECTED THROMBOTIC THROMBOCYTOPENIC PURPURA

    PubMed Central

    Parekh, Hiral D.; Reese, Jessica A.; Cobb, Patrick W.; George, James N.

    2014-01-01

    A 48 year-old white man was hospitalized for evaluation of back pain. At time he reported that he had been in excellent health until three months before his hospitalization when he noticed difficulty walking when he got out of his car following a long trip. He said that “it just felt as though my legs wouldn’t move very well”. He did not see a doctor since this problem resolved within several days. Three weeks before his hospitalization, he thought he “had a viral illness” with cough and fatigue that persisted, together with subsequent abdominal discomfort. His primary care physician noted that his platelet and white blood cell counts were low which he attributed to a viral infection. An abdominal ultrasound reported minimal splenomegaly. He was treated with antibiotics and prednisone; all of his symptoms resolved and his platelet count increased. One week before his hospitalization he developed low back pain which made walking difficult. He also had fever and sweats. When these symptoms persisted he was admitted to the hospital. His physical examination was normal. His spleen was not palpable; he had no lymphadenopathy; his neurologic examination, including his gait, was normal. He had no back tenderness. His platelet count was 23,000/µL; white blood cell count, 3700/µL with a normal differential; hemoglobin, 13.5 gm/dL; creatinine, 1.7 mg/dL; LDH, 1737 U/L (normal, <190 U/L). Coagulation tests were normal; fibrinogen was 858 mg/dL. Examination of the peripheral blood smear demonstrated schistocytes and normal white cell morphology. Thrombotic thrombocytopenic purpura (TTP) was suspected because of the thrombocytopenia, red cell fragmentation, high serum LDH and creatinine, the history of fever, the possibility that the difficulty walking may have been a neurologic manifestation of TTP, and – most important – no apparent alternative etiology. Treatment with plasma exchange (PEX) and corticosteroids was begun. PMID:25196665

  12. 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

  13. 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

  14. 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

  15. The Effects of Helicobacter pylori Eradication Therapy for Chronic Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Hwang, Jae Jin; Lee, Dong Ho; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

    2016-01-01

    Background/Aims The aim of this study was to evaluate the ability of Helicobacter pylori eradication treatment to increase platelet counts in Korean patients with chronic idiopathic thrombocytopenic purpura (ITP). Methods A total of 102 patients were evaluated against two criteria. First, those diagnosed with H. pylori infections in whom eradication was successful were assigned to the H. pylori-positive and -eradicated group (n=39), whereas those diagnosed with H. pylori infections in whom eradication failed were assigned to the H. pylori-positive and -non-eradicated group (n=3), and those without H. pylori infections were assigned to the H. pylori-negative group (n=60). Second, patients with complete remission in whom the platelet recovery effect was maintained over the average follow-up period of 6 months after eradication therapy were defined as the responder group (n=58), whereas those with partial or no response were defined as the nonresponder group (n=44). Results The platelet counts of the H. pylori-positive and -eradicated group were significantly increased 6 months after eradication therapy compared to those of the H. pylori-positive and -non-eradicated group and the H. pylori-negative group (43.2±29.1 to 155.3±68.7×103/μL vs 42.5±28.1 to 79.8±59.7×103/μL vs 43.1±28.9 to 81.2±62.2×103/μL; p=0.041). The eradication therapy success rate in the responder group was 100.0% (39/39), in contrast to the nonresponder group (0%, 0/3) (p<0.001). Conclusions H. pylori eradication therapy was related to increased platelet count, and successful eradication affected the increased platelet count in Korean patients with chronic ITP. PMID:26347517

  16. 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 μL. 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 μL. 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

  17. An infantile case of cytomegalovirus induced idiopathic thrombocytopenic purpura with predominant proliferation of CD10 positive lymphoblast in bone marrow.

    PubMed

    Mizutani, K; Azuma, E; Komada, Y; Ito, M; Sakurai, M; Hironaka, T; Hirai, K

    1995-02-01

    An infant with cytomegalovirus infection (CMV) developed idiopathic thrombocytopenic purpura (ITP) at 4 months of age. A bone marrow (BM) aspiration showed a remarkable increase of immature megakaryocytes and prominent proliferation of lymphoblasts. Flow cytometric analysis of the bone marrow cells showed that the predominant cells in the lymphocyte cluster were of B-lineage (CD19) with CD10 (common acute lymphoblastic leukemia antigen) positive. Virus study showed a higher titer of CMV antibody. Cytomegalovirus DNA was detected by the polymerase chain reaction (PCR) method in urine, peripheral cells and marrow cells. Low-grade fever, diarrhea and petechiae were accompanied by mild liver dysfunction. Complete remission was made with intravenous high-dose immunoglobulin (IVIg) without progression to overt acute leukemia. The percentage of CD10+/CD19+ lymphocytes in bone marrow also diminished. We postulated that the proliferation of immature lymphocytes and megakaryocytes in bone marrow was caused by maturation arrest that might result from CMV infection. PMID:7754772

  18. 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

  19. Low-dose vincristine in the treatment of corticosteroid-refractory idiopathic thrombocytopenic purpura (ITP) in non-splenectomized patients.

    PubMed Central

    Cervantes, F.; Montserrat, E.; Rozman, C.; Diumenjo, C.; Feliu, E.; Grañena, A.

    1980-01-01

    Eight non-splenectomized patients with corticosteroid-refractory idiopathic thrombocytopenic purpura (ITP) were treated with low-dose vincristine (1 mg/week up to a total dose of 4 mg). Complete remission was achieved in 2 cases and partial remission in 3. Bleeding stopped in one patient who failed to remit. No statistical relationship was found between the response to vincristine and the duration of the disease or the corticosteroid-therapy. Side effects were only observed in one patient. By comparing these results with those reported in the literature, it can be inferred that low-dose vincristine may be useful in the management of corticosteroid-refractory ITP. PMID:7194478

  20. Non-secreting benign glucagonoma diagnosed incidentally in a patient with refractory thrombocytopenic thrombotic purpura: report of a case.

    PubMed

    Georgiou, Georgios K; Gizas, Ioannis; Katopodis, Konstantinos P; Katsios, Christos S

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder, which may be idiopathic or secondary to a variety of diseases. However, there are very few reports of TTP in the context of pancreatic neoplasms. We report a case of relapsing TTP after initial treatment with plasmapheresis, corticosteroids, and rituximab, in a 59-year-old woman. During diagnostic work-up, a pancreatic lesion 35 × 25 mm in size was discovered incidentally and splenopancreatectomy was performed. The pathological diagnosis was benign glucagonoma. The hematological symptoms resolved completely after the procedure and 3 years later, the patient is well with no sign of recurrence of TTP or glucagonoma. To our knowledge, this represents the first documented case of a non-secreting benign pancreatic neuroendocrine tumor (glucagonoma) associated with TTP that is refractory to standard treatment. PMID:25373364

  1. 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

  2. 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

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

    PubMed Central

    Musa, Faisal; Baidas, Said

    2015-01-01

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

  4. 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

  5. Cardiac injury is a common postmortem finding in thrombotic thrombocytopenic purpura patients: is empiric cardiac monitoring and protection needed?

    PubMed

    Nichols, Larry; Berg, Aaron; Rollins-Raval, Marian A; Raval, Jay S

    2015-02-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease. Early implementation of therapeutic plasma exchange (TPE) has decreased the mortality rate from >90% to <10%. However, fatalities still occur in these patients. The goal of this study was to characterize the causes of death and related postmortem findings in patients with TTP in the current era of emergent TPE to identify possible areas for improvement in the care of these patients. We analyzed clinical history, laboratory and histopathologic findings, and causes of death of patients with active TTP or TTP in clinical remission autopsied at our institution over 22 years. Of 18 patients, 15 had TTP judged to be a cause of death: it was an underlying cause of death in five cases, intermediate in three, and contributing in seven. The most common immediate causes of death were cardiac arrest and myocardial infarction. The most common TTP-related findings at autopsy were thrombi/emboli in heart (9), lung (11), brain (3), kidney (7), followed by hemorrhages in heart (7), lung (8), brain (2), kidney (7), and infarcts in heart (5), lung (4), brain (6) and kidney (3). Analysis of the cases with TTP as a cause of death suggests that the mechanism of death is commonly cardiac in origin. Proactive measures to monitor and protect the heart may be beneficial in these patients. PMID:25196220

  6. Clinical Features and Treatment Outcomes of Primary Immune Thrombocytopenic Purpura in Hospitalized Children Under 2-Years Old

    PubMed Central

    Farhangi, H; Ghasemi, A; Banihashem, A; Badiei, Z; Jarahi, L; Eslami, G; Langaee, T

    2016-01-01

    Background Immune thrombocytopenic purpura (ITP) is the most prevalent cause of thrombocytopenia in children. Despite the importance of ITP in children under 2-years old, only a few publications are available in the literature.ITP usually presents itself as isolated thrombocytopenia and mucocutaneous bleeding. Materials and Methods This study was conducted on 187 under 2-year-old children diagnosed with ITP and treated at Dr. Sheikh Hospital from 2004 to 2011.In this retrospective study, clinical symptoms, laboratory findings, history of viral infections, vaccination history, and treatment efficacy in children under 2-years old with ITP were investigated.Patients were followed for one year after being discharged from the hospital. Results The risk of the disease developing into chronic form was higher in older children (0.001). ITP in children under 3-months old was significantly associated with vaccination (p=0.007). There was no significant differences between male and female patients in regards to newly diagnosed ITP, persistent, and chronic disease status (p = 0.21). No significant difference in bleeding symptoms was observed between patients under 3-months old and 3 to 24-months old (p=0.18). Conclusion Infantile ITP respond favorably to treatment. The risk of the disease developing into chronic form is higher in 3-to-24-month-old children compared to under-three-month olds.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura.

    PubMed

    Ramírez-Alejo, Noé; Alcántara-Montiel, Julio C; Yamazaki-Nakashimada, Marco; Duran-McKinster, Carola; Valenzuela-León, Paola; Rivas-Larrauri, Francisco; Cedillo-Barrón, Leticia; Hernández-Rivas, Rosaura; Santos-Argumedo, Leopoldo

    2015-10-01

    NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. PMID:26117626

  14. Late-Onset Immune Thrombocytopenic Purpura After Withdrawal of Interferon Treatment for Chronic Hepatitis C Infection: A Case Report.

    PubMed

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

    2015-08-01

    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 × 10 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

  15. Validity of a procedure to identify patients with chronic idiopathic thrombocytopenic purpura in the Danish National Registry of Patients

    PubMed Central

    Heden, Katrine Edith Klith; Jensen, Annette Østergaard; Farkas, Dora Körmendiné; Nørgaard, Mette

    2009-01-01

    Background: Administrative data may be useful for epidemiological studies of chronic idiopathic thrombocytopenic purpura (ITP). However, the quality of the recorded diagnoses needs evaluation. Aim: We evaluated the validity in predicting chronic ITP of the International Classification of Diseases (ICD)-10 diagnoses of ITP in the Danish National Registry of Patients (NRP). Methods: We used the NRP to identify patients with ITP, according to code D69.3, from January 1, 1996 to December 31, 2007. We defined chronic ITP as lasting longer than 6 months by including only patients with 2 or more hospital ITP diagnoses over longer than 6 months. We confirmed diagnoses by evaluating each candidate chronic ITP patient’s medical chart and estimating the positive predictive value (PPV) and 95% confidence interval (CI) of the recorded NRP diagnostic code. Results: We identified 513 patients with chronic ITP in the NRP. We were able to retrieve the charts of 439. After evaluation of the charts, 410 patients were deemed to have a valid diagnosis of chronic ITP, yielding a PPV of 0.93 (95% CI: 0.91–0.96). Conclusion: The validity of this procedure to identify chronic ITP patients was high. The NRP is valid for epidemiological studies of patients with chronic ITP. PMID:20865080

  16. 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

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

    PubMed

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

    2014-01-01

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

  18. 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

  19. 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

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

    PubMed

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

    2007-01-01

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

  1. Differential effect of corticosteroids on serum cystatin C in thrombocytopenic purpura and leukemia.

    PubMed

    Bardi, Edit; Dobos, Eva; Kappelmayer, János; Kiss, Csongor

    2010-09-01

    The aim of our study was to evaluate the influence of steroid therapy on serum cystatin C (cysC) concentrations in patients with acute lymphoblastic leukemia (ALL) and idiopthiás thrombocytopenias purpura (ITP). We studied 17 patients with ITP (girls: boys =5:12, mean age: 7.6 yrs, range between 1 to 17 years) and 18 patients with ALL (girls: boys =6:12, mean age: 6.3 yrs, range between 2 to 17 years). CysC and white blood cell count (WBC) in both group of patients were determined before and after 300 mg/m(2) cumulative dose of steroid therapy. Corticosteroids increased the level of cysC in both groups of patients, however significant increase was found only in ITP patients between pre- and posttreatment values (0.96 +/-0.27 mg/L vs. 1.16 +/- 0.3 mg/L, p =0,02). Pretreatment cysC concentrations were within the reference range in patients with ITP but not with ALL and were significantly higher in ALL patients, than in ITP patients (1.23 +/- 1,12 mg/L vs. 0.96 +/- 0.27 mg/L, p =0,02). Pretreatment WBC of ALL patients were significantly higher than of ITP patients (22.58 G/L, min. 3.5 G/L, max. 102.1 G/L vs. 7.46 G/L, min. 4.8 G/L, max. 12.3 G/L, p =0.03). We have found significant correlation between pretreatment cysC and WBC values in ALL patients (p = 0.04). Although the concentration of cysC may be slightly and reversibly influenced by corticosteroid treatment, cysC is sensitive to detect early and moderate deterioration of GFR in children with cancer. PMID:20084479

  2. 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

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

    PubMed Central

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

    2014-01-01

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

  4. 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

  5. Immune Thrombocytopenic Purpura During Maintenance Phase of Acute Lymphoblastic Leukemia: A Rare Coexistence Requiring a High Degree of Suspicion, a Case Report and Review of the Literature

    PubMed Central

    Bayhan, Turan; Ünal, Şule; Gümrük, Fatma; Çetin, Mualla

    2015-01-01

    Thrombocytopenia may develop in patients with acute lymphoblastic leukemia (ALL) due to myelosuppression of chemotherapy or relapse. Here we report a pediatric patient with ALL whose platelet counts decreased at the 102nd week of maintenance treatment. Thrombocytopenia was refractory to platelet infusions and bone marrow aspiration revealed remission status for ALL along with increased megakaryocytes. The cessation of chemotherapy for 2 weeks caused no increase in thrombocyte counts. The viral serology was unrevealing. A diagnosis of immune thrombocytopenic purpura (ITP) was established. After administration of intravenous immunoglobulin, the thrombocytopenia resolved. When thrombocytopenia occurs in patients with ALL in remission, ITP should be kept in mind after exclusion of the more common etiologies. PMID:25913619

  6. Immune Thrombocytopenic Purpura During Maintenance Phase of Acute Lymphoblastic Leukemia: A Rare Coexistence Requiring a High Degree of Suspicion, a Case Report and Review of the Literature.

    PubMed

    Bayhan, Turan; Ünal, Şule; Gümrük, Fatma; Çetin, Mualla

    2015-12-01

    Thrombocytopenia may develop in patients with acute lymphoblastic leukemia (ALL) due to myelosuppression of chemotherapy or relapse. Here we report a pediatric patient with ALL whose platelet counts decreased at the 102nd week of maintenance treatment. Thrombocytopenia was refractory to platelet infusions and bone marrow aspiration revealed remission status for ALL along with increased megakaryocytes. The cessation of chemotherapy for 2 weeks caused no increase in thrombocyte counts. The viral serology was unrevealing. A diagnosis of immune thrombocytopenic purpura (ITP) was established. After administration of intravenous immunoglobulin, the thrombocytopenia resolved. When thrombocytopenia occurs in patients with ALL in remission, ITP should be kept in mind after exclusion of the more common etiologies. PMID:25913619

  7. [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

  8. Thrombotic Thrombocytopenic Purpura

    MedlinePlus

    ... and Marrow Stem Cell Transplant Excessive Blood Clotting Hemolytic Anemia Send a link to NHLBI to someone by ... the body can replace them. This leads to hemolytic anemia (HEE-moh-lit-ick uh-NEE-me-uh)— ...

  9. Thrombotic thrombocytopenic purpura

    MedlinePlus

    ... also may be caused by: Cancer Chemotherapy Hematopoietic stem cell transplantation HIV infection Hormone replacement therapy and estrogens Medicines (including ticlopidine, clopidogrel, guinine, and cyclosporine A)

  10. Impact of chronic Immune Thrombocytopenic Purpura (ITP) on health-related quality of life: a conceptual model starting with the patient perspective

    PubMed Central

    Mathias, Susan D; Gao, Sue K; Miller, Kimberly L; Cella, David; Snyder, Claire; Turner, Ralph; Wu, Albert; Bussel, James B; George, James N; McMillan, Robert; Wysocki, Diane Kholos; Nichol, Janet L

    2008-01-01

    Background Immune thrombocytopenic purpura (ITP), a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL). Methods A literature search and focus groups with adult ITP patients were conducted to identify areas of HRQoL affected by ITP. Published literature was reviewed to identify key HRQoL issues and existing questionnaires used to assess HRQoL. Focus group transcripts were reviewed, and common themes were extracted by grouping conceptual categories that described the impact on HRQoL. Results The literature synthesis and themes from the focus group data suggest that decreased platelet counts, disease symptoms, and treatment side effects influence multiple domains of HRQoL for ITP patients. Key areas affected by ITP and its treatments include emotional and functional health, work life, social and leisure activities, and reproductive health. Conclusion ITP affects various areas of HRQoL. This conceptual model will help inform the evaluation of therapeutic strategies for ITP. PMID:18261217

  11. Mutation of the H-bond acceptor S119 in the ADAMTS13 metalloprotease domain reduces secretion and substrate turnover in a patient with congenital thrombotic thrombocytopenic purpura.

    PubMed

    Feys, Hendrik B; Pareyn, Inge; Vancraenenbroeck, Renee; De Maeyer, Marc; Deckmyn, Hans; Van Geet, Chris; Vanhoorelbeke, Karen

    2009-11-19

    Hereditary thrombotic thrombocytopenic purpura is caused by mutations in a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS13) resulting in defective processing of von Willebrand factor (VWF) that causes intravascular platelet aggregation culminating in thrombocytopenia with shistocytic anemia. In this study the functional and structural role of a recently identified ADAMTS13 metalloprotease domain mutation S119F was investigated. Secretion from heterologous cells was hampered but not completely eliminated. Secreted S119F was active toward multimeric VWF and FRETS-VWF73 but with abnormal kinetics, having a significantly reduced overall catalytic rate (k(cat); 0.88 +/- 0.04 s(-1) vs 2.78 +/- 0.11 s(-1)) and slightly smaller Michaelis constant (K(M); 1.4 +/- 0.2microM vs 2.3 +/- 0.3microM). A computational model of the metalloprotease domain demonstrates both steric and polar interaction effects caused by S119F. Interestingly, mutant S119A has properties similar to S119F (k(cat) = 0.82 +/- 0.03 s(-1) and K(M) = 1.1 +/- 0.1microM), allowing to assign distorted kinetics to the loss of the H-bond with conserved residue W262. We conclude that the S119-W262 H-bond is crucial for maximal turnover. PMID:19786614

  12. 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.

  13. 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.

  14. 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

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

    PubMed

    Gangarossa, S; Mattina, T; Romano, V; Milana, G; Mollica, F; Schilirò, 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. PMID:8882392

  16. 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

  17. 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.

  18. Endobronchial hemorrhage after intubation with double-lumen endotracheal tube in a patient with idiopathic thrombocytopenic purpura for minimally invasive cardiac surgery: a case report.

    PubMed

    Kim, Hee Young; Baek, Seung Hoon; Kim, Kyoung Hoon; Kim, Nam Won

    2014-01-01

    Minimally invasive cardiac surgery (MICS) requires lung isolation. Lung isolation is usually achieved with double-lumen endotracheal tube (DLT). Patients with idiopathic thrombocytopenic purpura (ITP) have an increased risk of bleeding events. We suspected endobronchial hemorrhage after exchange of DLT during induction of anesthesia for replacement of mitral valve in a 62-year-old man with a known ITP. The MICS was stopped and bronchial artery embolization was performed in the angiographic room. In the present case, in order to reduce the risk of bronchial arterial injury in ITP patient we intubated with single lumen endotracheal tube. Lung isolation led to achievement of intermittent total lung deflation. Based on the results, we recommend a high-dose intravenous immunoglobulin therapy and platelet transfusion prior to cardiac surgery in patients with ITP to increase platelet count. Moreover, it is proposed that in order to clear the vision during the operation, ventilation can be held or made intermittent both prior to cardiopulmonary bypass or at its conclusion to permit exposure. PMID:24567815

  19. Endobronchial hemorrhage after intubation with double-lumen endotracheal tube in a patient with idiopathic thrombocytopenic purpura for minimally invasive cardiac surgery: a case report

    PubMed Central

    Kim, Hee Young; Kim, Kyoung Hoon; Kim, Nam Won

    2014-01-01

    Minimally invasive cardiac surgery (MICS) requires lung isolation. Lung isolation is usually achieved with double-lumen endotracheal tube (DLT). Patients with idiopathic thrombocytopenic purpura (ITP) have an increased risk of bleeding events. We suspected endobronchial hemorrhage after exchange of DLT during induction of anesthesia for replacement of mitral valve in a 62-year-old man with a known ITP. The MICS was stopped and bronchial artery embolization was performed in the angiographic room. In the present case, in order to reduce the risk of bronchial arterial injury in ITP patient we intubated with single lumen endotracheal tube. Lung isolation led to achievement of intermittent total lung deflation. Based on the results, we recommend a high-dose intravenous immunoglobulin therapy and platelet transfusion prior to cardiac surgery in patients with ITP to increase platelet count. Moreover, it is proposed that in order to clear the vision during the operation, ventilation can be held or made intermittent both prior to cardiopulmonary bypass or at its conclusion to permit exposure. PMID:24567815

  20. 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

  1. 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

  2. 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 1068 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?

  3. 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

  4. Congenital amegakaryocytic thrombocytopenic purpura (CAMT).

    PubMed

    Ghauri, Rooha Ijaz; Naveed, Muhammad; Mannan, Jovaria

    2014-04-01

    Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL) despite high levels of serum TPO. Patients initially present with isolated thrombocytopenia that subsequently progresses into pancytopenia. Although the mechanisms leading to aplasia are unknown, the age of onset has been reported to depend on the severity of the c-MPL functional defect. The primary treatment for CAMT is bone marrow transplantation. This report describes a newborn girl who presented to us with symptoms of sepsis but septic profile came negative except thrombocytopenia. Bone marrow biopsy was done for thrombocytopenia which revealed amegakaryocytic thrombocytopenia. She was given prednisolone. PMID:24709246

  5. Study of platelet-associated immunoglobulins of IgG, IgM, IgA, and IgE classes and platelet kinetics in 33 patients with idiopathic thrombocytopenic purpura.

    PubMed

    Movahed Shariat Panahi, M R; Le Blanc, S; Schober, O; Coldewey, R; Deicher, H

    1994-09-01

    The role of platelet-associated immunoglobulins (PAIg) of four different immunoglobulin classes--IgM, IgG, IgA, and IgE--and their relation to platelet count and platelet kinetics was studied in 33 patients with idiopathic thrombocytopenic purpura (ITP). During the course of 1 year, repeated determinations of PAIg were made. The results indicate that PAIgG, PAIgM, and PAIgA are present in all ITP patients, and that autoantibodies of all three Ig classes show highly significant correlations to the platelet counts (p < 0.0001). Double logarithmic negative correlations have been found between PAIgG and platelet count (r = -0.71), PAIgM and platelet count (r = -0.84), and PAIgA and platelet count (r = -0.79). Statistical analyses using partial correlation and multiple regression methods showed that PAIgM is predominantly related to the platelet count, whereas PAIgG and PAIgA are only of secondary importance. Accordingly, a relation of PAIgM (and PAIgA) to increased liver destruction of platelets was found in kinetic studies using 111indium-labeled platelets. Taken together, these results suggest a predominant role of PAIgM in the pathogenesis of ITP. PMID:8086506

  6. Clinical significance of HLA-DR+, CD19+, CD10+ immature B-cell phenotype and CD34+ cell detection in bone marrow lymphocytes from children affected with immune thrombocytopenic purpura.

    PubMed

    Callea, V; Comis, M; Iaria, G; Sculli, G; Morabito, F; Lombardo, V T

    1997-01-01

    In children with immune thrombocytopenic purpura (ITP), bone marrow lymphocytes can express the common acute lymphoblastic leukemia antigen (CALLA) pattern with no evidence of leukemia or lymphoma. Bone marrow lymphocytes from 23 children and 20 adults affected with ITP were studied to determine the incidence and the clinical impact of lymphocytes with the immature B-cell phenotype and CD34+ cell expression. In this investigation we identified a group consisting of 52% of the children who showed the immature B phenotype, while the remaining 48%, similarly to adult ITP displayed an increase of T-cell antigens. CD34 was positive in 53% of children, but it was present in only half of the patients with the immature B phenotype and it was always absent in adults. IgH genes disclosed a germline configuration in all six patients in the immature B phenotype group. No difference was found in the two groups of children in terms of age, presentation of the disease or final outcome. Finally, no patient in either children's group has developed an acute lymphoproliferative disorder. PMID:9299867

  7. Genetics Home Reference: thrombotic thrombocytopenic purpura

    MedlinePlus

    ... blood cells can break apart. A condition called hemolytic anemia occurs when red blood cells are destroyed faster ... Schulman syndrome MedlinePlus Encyclopedia: Blood Clots MedlinePlus Encyclopedia: Hemolytic ... Encyclopedia: Thrombocytopenia MedlinePlus Encyclopedia: ...

  8. How Is Thrombotic Thrombocytopenic Purpura Diagnosed?

    MedlinePlus

    ... and Marrow Stem Cell Transplant Excessive Blood Clotting Hemolytic Anemia Send a link to NHLBI to someone by ... find out whether TTP is the cause of hemolytic anemia . For this test, a sample of blood is ...

  9. 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 ...

  10. 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

  11. 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

  12. Idiopathic thrombocytopenic purpura following successful treatment of acute lymphoblastic leukemia.

    PubMed

    Tannir, N M; Kantarjian, H

    2001-03-01

    Thrombocytopenia is common in patients with acute lymphocytic leukemia (ALL) at diagnosis. It is a universal side effect of dose-intensive regimens employed in the treatment of adult ALL. In patients with ALL who achieve remission, thrombocytopenia frequently indicates relapse. We report three adult patients successfully treated for ALL who developed thrombocytopenia and were found to have immune-mediated thrombocytopenia (ITP). Possible pathophysiologic mechanisms underlying the association of ALL and ITP are discussed. PMID:11342378

  13. Systemic lupus erythematosus and thrombotic thrombocytopenia purpura: a refractory case without lupus activity.

    PubMed

    Garcia Boyero, Raimundo; Mas Esteve, Eva; Mas Esteve, Maria; Millá Perseguer, M Magdalena; Marco Buades, Josefa; Beltran Fabregat, Juan; Cañigral Ferrando, Guillermo; Belmonte Serrano, Miguel Angel

    2013-01-01

    The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab. PMID:23473755

  14. 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)

  15. Fc receptors in immune thrombocytopenias: a target for immunomodulation?

    PubMed Central

    Psaila, Bethan; Bussel, James B.

    2008-01-01

    In autoimmune disease, Fc receptors (FcRs) form the interface between immune effector cells and their antibody-coated targets, and as such are attractive targets for immunomodulatory therapy. In this issue of the JCI, two highly novel studies of Fc–FcR interactions provide new insights into the role of FcRs in immune thrombocytopenia. Asahi et al. utilized a comprehensive platform of immunological assays to examine the mechanism underlying Helicobacter pylori–associated immune thrombocytopenic purpura, and Ghevaert et al. describe a specially designed antibody that saturates binding sites on fetal platelets without initiating FcγR-mediated platelet phagocytosis, preventing the binding of pathological maternal anti-HLA antibodies that cause fetomaternal alloimmune thrombocytopenia (see the related articles beginning on pages 2939 and 2929, respectively). These reports illustrate how a remarkably detailed molecular understanding of the FcR network may translate into new therapeutic strategies with high clinical impact. PMID:18654670

  16. A non-thrombocytopenic bleeding disorder due to an IgG4-kappa anti-GPIIb/IIIa autoantibody.

    PubMed

    McMillan, R; Bowditch, R D; Tani, P; Anderson, H; Goodnight, S

    1996-12-01

    Autoantibodies in chronic immune thrombocytopenic purpura occasionally interfere with platelet function. We describe a patient with a normal platelet count who had clinically significant mucosal bleeding, a prolonged bleeding time and abnormal platelet aggregation. The patient had high titres of an IgG4 kappa autoantibody, directed to a cation-dependent epitope on platelet glycoprotein IIb/IIIa, which blocked the binding of fibrinogen and fibronectin to this complex. Corticosteroid treatment resulted in clinical improvement and a marked drop in autoantibody concentration. The lack of thrombocytopenia in this patient, despite high autoantibody levels, is best explained by the poor recognition of IgG4 antibodies by phagocytic cells. PMID:8982055

  17. 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. ...

  18. Powerlifter's purpura: a valsalva-associated phenomenon.

    PubMed

    Pierson, Joseph C; Suh, Philip S

    2002-08-01

    The causes of purpura can be classified into intravascular, vascular, and extravascular mechanisms. We describe a case of cervicofacial purpura in a powerlifter attributed to the accompanying Valsalva-associated increased arterial pressure. Powerlifting should be added to the list of activities that may cause purpura. PMID:12234164

  19. 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

  20. Immunthrombocytopenic purpura as a model for pathogenesis and treatment of autoimmunity.

    PubMed

    Imbach, P; Akatsuka, J; Blanchette, V; Burek-Kozlowska, A; Bussel, J; Gaedicke, G; Gianella-Borradori, A; Gugler, E; Hirt, A; Imholz, B

    1995-01-01

    In honour of Professor Rossi's 80th birthday we review the development of our understanding of the immune and auto-immune nature of the pathogenesis of immune thrombocytopenic purpura (ITP). The immune aspects have been documented by postviral alterations of the cellular and humoral immune system, by new methods of specific auto-antibody detection against platelet glycoproteins and by the therapeutic effect of administering immunoglobulin concentrate from healthy blood donors. The various possible mechanisms of action of immunoglobulin treatment have led to use of this treatment as an alternative for other immune-related disorders. The treatment of severe chronic ITP in children, however, remains unsatisfactory. With a new international clinical and laboratory study of children and adolescents with early chronic ITP we are continuing the investigation of the pathogenesis and treatment of ITP. PMID:8529713

  1. [Orthostatic purpura: report of two cases].

    PubMed

    Sawada, Y; Kudo, I; Kanazawa, T; Aihara, M; Yoshida, Y; Kimura, A; Chiba, Y

    1991-12-01

    Two patients with orthostatic purpura were reported. Case 1: A 47-year-old man was admitted to our institution because of multiple purpuric eruptions over the legs after the long periods of sitting or standing. Bleeding time was 4.0 min. Platelet aggregation induced by ADP was disaggregated and no aggregation was observed when induced by collagen and epinephrine. He was diagnosed as having release abnormality of the platelets caused by glutathione administered for treatment of liver damage for several years. Purpura, however, appeared even though platelet function became normal after discontinuing glutathione. Purpura proved to be induced by the long periods of sitting or standing. Case 2: A 37-year-old woman was admitted to our hospital because of purpuric eruptions over the legs for three years. Bleeding time was 2.0 min. Platelet aggregation induced by ADP, epinephrine, collagen and ristocetin was normal. Purpura was caused by long periods of standing without movement. Wearing elastic pantyhose showed reduced appearance of the purpura. Biopsy specimens from both patients revealed no abnormal findings. Both patients had no abnormal results in coagulation studies. Purpura seemed to be caused by the increased capillary pressure after the prolonged periods of standing. No case report concerning orthostatic purpura or mechanical purpura has been published. PMID:1779458

  2. 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.

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

    PubMed Central

    Kuonen, Franois; 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

  4. 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 organisms 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

  5. 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

  6. Indian tick typhus presenting as Purpura fulminans

    PubMed Central

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

    2014-01-01

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

  7. 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

  8. 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

  9. Henoch-Schönlein purpura with preceding abdominal pain.

    PubMed

    Toshihiko, Kakiuchi; Tomonobu, Aoki

    2015-06-01

    Diagnosing HSP can be difficult, especially when abdominal symptoms precede the onset of characteristic palpable purpura (Chen MJ et al. 2005, World Gastroenterol., 11, 2354). Therefore, it is necessary to consider the possibility of HSP in patients with prolonged strong abdominal pain, even in cases without purpura. PMID:26185663

  10. 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. PMID:26839767

  11. 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

  12. Diabetes and immune thrombocytopenic purpura: a new association with good response to anti-CD20 therapy.

    PubMed

    von Laer Tschudin, Letizia; Schwitzgebel, Valérie M; von Scheven-Gête, Annette; Blouin, Jean-Louis; Hofer, Michael; Hauschild, Michael; Ansari, Marc; Stoppa-Vaucher, Sophie; Phan-Hug, Franziska

    2015-03-01

    Type 1 diabetes (T1D) is rarely a component of primary immune dysregulation disorders. We report two cases in which T1D was associated with thrombocytopenia. The first patient, a 13-year-old boy, presented with immune thrombocytopenia (ITP), thyroiditis, and, 3 wk later, T1D. Because of severe thrombocytopenia resistant to immunoglobulins, high-dose steroids, and cyclosporine treatment, anti-cluster of differentiation (CD20) therapy was introduced, with consequent normalization of thrombocytes and weaning off of steroids. Three and 5 months after anti-CD20 therapy, levothyroxin and insulin therapy, respectively, were stopped. Ten months after stopping insulin treatment, normal C-peptide and hemoglobin A1c (HbA1c) levels and markedly reduced anti-glutamic acid decarboxylase (GAD) antibodies were measured. A second anti-CD20 trial for relapse of ITP was initiated 2 yr after the first trial. Anti-GAD antibody levels decreased again, but HbA1c stayed elevated and glucose monitoring showed elevated postprandial glycemia, demanding insulin therapy. To our knowledge, this is the first case in which insulin treatment could be interrupted for 28 months after anti-CD20 treatment. In patient two, thrombocytopenia followed a diagnosis of T1D 6 yr previously. Treatment with anti-CD20 led to normalization of thrombocytes, but no effect on T1D was observed. Concerning the origin of the boys' conditions, several primary immune dysregulation disorders were considered. Thrombocytopenia associated with T1D is unusual and could represent a new entity. The diabetes manifestation in patient one was probably triggered by corticosteroid treatment; regardless, anti-CD20 therapy appeared to be efficacious early in the course of T1D, but not long after the initial diagnosis of T1D, as shown for patient two. PMID:24552605

  13. 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.

  14. A role for plasma cell targeting agents in immune tolerance induction in autoimmune disease and antibody responses to therapeutic proteins.

    PubMed

    Rosenberg, A S; Pariser, A R; Diamond, B; Yao, L; Turka, L A; Lacana, E; Kishnani, P S

    2016-04-01

    Antibody responses to life saving therapeutic protein products, such as enzyme replacement therapies (ERT) in the setting of lysosomal storage diseases, have nullified product efficacy and caused clinical deterioration and death despite treatment with immune-suppressive therapies. Moreover, in some autoimmune diseases, pathology is mediated by a robust antibody response to endogenous proteins such as is the case in pulmonary alveolar proteinosis, mediated by antibodies to Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). In this work, we make the case that in such settings, when the antibody response is high titered, sustained, and refractory to immune suppressive treatments, the antibody response is mediated by long-lived plasma cells which are relatively unperturbed by immune suppressants including rituximab. However, long-lived plasma cells can be targeted by proteasome inhibitors such as bortezomib. Recent reports of successful reversal of antibody responses with bortezomib in the settings of ERT and Thrombotic Thrombocytopenic Purpura (TTP) argue that the safety and efficacy of such plasma cell targeting agents should be evaluated in larger scale clinical trials to delineate the risks and benefits of such therapies in the settings of antibody-mediated adverse effects to therapeutic proteins and autoantibody mediated pathology. PMID:26928739

  15. 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

  16. 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

  17. Massive soft tissue infections: necrotizing fasciitis and purpura fulminans.

    PubMed

    Edlich, Richard F; Winters, Kathryne L; Woodard, Charles R; Britt, L D; Long, William B

    2005-01-01

    Necrotizing fasciitis and purpura fulminans are two destructive infections that involve both skin and soft tissue. Necrotizing fasciitis is characterized by widespread necrosis of subcutaneous tissue and the fascia. Historically, group A beta-hemolytic streptococcus has been identified as a major cause of this infection. However, this monomicrobial infection is usually associated with some underlying cause, such as diabetes mellitus. During the last two decades, scientists have found that the pathogenesis of necrotizing fasciitis is polymicrobial. The diagnosis of necrotizing fasciitis must be made as soon as possible by examining the skin inflammatory changes. Magnetic resonance imaging is strongly recommended to detect the presence of air within the tissues. Percutaneous aspiration of the soft tissue infection followed by prompt Gram staining should be conducted with the "finger-test" and rapid-frozen section biopsy examination. Intravenous antibiotic therapy is one of the cornerstones of managing this life-threatening skin infection. Surgery is the primary treatment for necrotizing fasciitis, with early surgical fasciotomy and debridement. Following debridement, skin coverage by either Integra Dermal Regeneration Template or AlloDerm should be undertaken. Hyperbaric oxygen therapy complemented by intravenous polyspecific immunoglobulin are useful adjunctive therapies. Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin; it is rapidly progressive and accompanied by vascular collapse. There are three types of purpura fulminans: neonatal purpura fulminans, idiopathic or chronic purpura fulminans, and acute infectious purpura fulminans. Clinical presentation of purpura fulminans involves a premonitory illness followed by the rapid development of a septic syndrome with fever, shock, and disseminated intravascular coagulation. The diagnosis and treatment of these conditions is best accomplished in a regional burn center in which management of multiple organ failure can be conducted with aggressive debridement and fasciotomy of the necrotic skin. The newest revolutionary advancement in the treatment of neonatal purpura fulminans is the use of activated protein C. PMID:15715517

  18. 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

  19. Staphylococcal Purpura Fulminans: Report of a Case.

    PubMed

    Honarpisheh, Hedieh; Camp, Robert; Lazova, Rossitza

    2015-08-01

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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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. PMID:26889120

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

    PubMed

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

    2014-04-01

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

  6. Ultralarge von Willebrand factor-induced platelet clumping and activation of the alternative complement pathway in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndromes.

    PubMed

    Turner, Nancy; Sartain, Sarah; Moake, Joel

    2015-06-01

    The molecular linkage between ultralarge (UL) von Willebrand factor (VWF) multimers and the alternative complement pathway (AP) has recently been described. Endothelial cell (EC)-secreted and anchored ULVWF multimers (in long stringlike structures) function as both hyperadhesive sites that initiate platelet adhesion and aggregation and activating surfaces for the AP. In vitro, the active form of C3, C3b binds to the EC-anchored ULVWF multimeric strings and initiates the assembly on the strings of C3 convertase (C3bBb) and C5 convertase (C3bBbC3b). In vivo, activation of the AP via this mechanism proceeds all the way to generation of terminal complement complexes (C5b-9). PMID:26043389

  7. Acute Scrotal Swelling in Henoch-Schonlein Purpura: Case Report and Review of the Literature

    PubMed Central

    Modi, Sunny; Mohan, Muhunthan; Jennings, Andrew

    2016-01-01

    Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized classically by purpura, arthritis and abdominal pain. Epididymitis/orchitis is rarely seen as a complication of HSP. Testicular or scrotal involvement has been reported in children with Henoch-Schonlein purpura and must be distinguished from testicular torsion. We report a case of a 5 year old boy diagnosed with Henoch-Schönlein purpura with acute scrotal swelling. He was managed successfully with conservative approach. The history, clinical examination findings and scrotal ultrasound evaluation should suffice to make the correct diagnosis and avoid surgery. Steroid treatment and/or antibiotics appeared to be effective for this condition. PMID:27169017

  8. Acute Scrotal Swelling in Henoch-Schonlein Purpura: Case Report and Review of the Literature.

    PubMed

    Modi, Sunny; Mohan, Muhunthan; Jennings, Andrew

    2016-05-01

    Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized classically by purpura, arthritis and abdominal pain. Epididymitis/orchitis is rarely seen as a complication of HSP. Testicular or scrotal involvement has been reported in children with Henoch-Schonlein purpura and must be distinguished from testicular torsion. We report a case of a 5 year old boy diagnosed with Henoch-Schönlein purpura with acute scrotal swelling. He was managed successfully with conservative approach. The history, clinical examination findings and scrotal ultrasound evaluation should suffice to make the correct diagnosis and avoid surgery. Steroid treatment and/or antibiotics appeared to be effective for this condition. PMID:27169017

  9. 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

  10. 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

  11. /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.

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

    PubMed

    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. PMID:26955583

  13. [A case of ureteritis in Henoch-Shnlein purpura].

    PubMed

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

    2006-01-01

    Henoch-Schnlein 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

  14. 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. PMID:26955583

  15. 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

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

    PubMed

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

    2014-11-01

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

  17. [Massive colorectal hemorrhage in adult Schönlein-Henoch purpura].

    PubMed

    Novák, J; Libor, J

    1993-07-01

    Schönlein-Henoch purpura is a well known syndrome, rare in adults, and is seldom accompanied with extensive colorectal haemorrhage. In abdominal purpura, the small bowel is more frequently involved, but cases of oesophageal, gastroduodenal and colorectal localisation also have been reported. The cases with colorectal bleeding, appearing in adulthood and elderly patients, could cause differential diagnostic problems. Described endoscopic features of one patient, who was referred to our department, because of colorectal bleeding. The treatment, course of disease and endoscopic follow-up is presented. No previous endoscopic documentation of this type of localisation has been reported in Hungarian literature, so far. PMID:8351133

  18. 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

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

    PubMed

    Feci, Luca; Fimiani, Michele; Rubegni, Pietro

    2015-10-01

    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

  20. A case of anaphylactoid purpura nephritis accompanied by pulmonary hemorrhage and review of the literature

    PubMed Central

    REN, XIANQING; ZHANG, WENJUAN; DANG, WEILI; ZHAI, WENSHENG; GUO, QINGYIN; DING, YIN; YANG, XIAOQING

    2013-01-01

    Cases of Henoch-Schönlein purpura and purpura nephritis accompanied by pulmonary hemorrhage are rare. Mild cases are easily ignored due to a lack of evident bleeding, and severe cases may be fatal. We have only treated one patient with Henoch-Schönlein nephritis (HSPN), a female child. The clinical manifestations were not evident, however, the imaging manifestations were clear. Finally, the patient was definitively diagnosed with HSPN accompanied by pulmonary hemorrhage. Following treatment with antiinflammatory and steroidal agents, tripterygium glycosides and traditional Chinese medicine, the patient recovered. In the present study, we report the diagnosis and treatment of this disease, with a review of the literature. PMID:23737885

  1. 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

  2. Mathematical model of platelet turnover in thrombocytopenic and nonthrombocytopenic preterm neonates

    PubMed Central

    Kulshrestha, Mudit; Sola-Visner, Martha; Widness, John A.; Veng-Pedersen, Peter

    2014-01-01

    Neonatal thrombocytopenia affects 22–35% of all neonates admitted to neonatal intensive care units. The purpose of this study was to develop a mathematical model for characterizing platelet (PLT) kinetics in thrombocytopenic preterm neonates. Immature PLT fraction (IPF) and PLT counts were measured for up to 35 days after birth in 27 very low birth weight preterm neonates. PLT transfusions were administered to 8 of the 27 (24%) subjects. The final model included a series of four transit compartments to mimic the production and survival of IPF and PLT. Model parameters were estimated using nonlinear mixed effects modeling with the maximum likelihood expectation maximization algorithm. The model adequately captured the diverse phenotypes expressed by individual subject profiles. Typical population survival values for IPF and PLT life spans in nonthrombocytopenic patients were estimated at 0.912 and 10.7 days, respectively. These values were significantly shorter in thrombocytopenic subjects, 0.429 and 2.56 days, respectively. The model was also used to evaluate the influence of growth and laboratory phlebotomy loss on the time course of IPF and PLT counts. Whereas incorporating body weight was essential to correct for expanding blood volume due to growth, phlebotomy loss, a possible covariate, did not significantly influence PLT kinetics. This study provides a platform for identifying potential covariates that influence the interindividual variability in model parameters regulating IPF and PLT kinetics and for evaluating future pharmacological therapies for treating thrombocytopenic neonates. PMID:25362135

  3. 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

  4. 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

  5. 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

  6. Posterior reversible encephalopathy syndrome in a child with Henoch-Schönlein purpura

    PubMed Central

    Sivrioglu, Ali Kemal; Incedayi, Mehmet; Mutlu, Hakan; Meral, Cihan

    2013-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel vasculitis that affects the gastrointestinal and central nervous systems and the kidneys. The disease primarily affects children, but may occur in elderly children with allergic purpura and also in adults. Central nervous system involvement may be the first sign; however, it is rarely encountered. Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome of encephalopathy, headache, visual disturbance and seizures. Its radiological signs can be observed in grey and white matter at the posterior region of the cerebral hemispheres. HSP should be considered in children with PRES in the presence of rash, joint and gastrointestinal symptoms. We reported a 5-year-old patient who developed acute renal failure and PRES by reason of HSP. PMID:23946524

  7. Terminal Ileitis as a Feature of Henoch-Schnlein Purpura Masquerading as Crohn Disease in Adults.

    PubMed

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

    2016-03-01

    Henoch-Schnlein 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

  8. 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

  9. Mycoplasma pneumoniae as a trigger for Henoch-Schnlein 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-Schnlein 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-Schnlein 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-Schnlein purpura, Mycoplasma pneumonia infection may be a potential cause of exacerbation of the disease. PMID:26862316

  10. 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

  11. 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

  12. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

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

  13. Purpura fulminans -- soft tissue damage as a manifestation of bacterial sepsis.

    PubMed

    Klebanovas, J; Barauskas, V; Cekanauskas, E; Malcius, D; Grinkeviciute, D

    2005-04-01

    We present here two cases of purpura fulminans (PF), a rare complication of septicemia. Its fulminant course usually prompt the surgeon into quick and aggressive action. Although sometimes it may lead to mutilation of a patient, nevertheless it is a life-saving procedure. A decision to amputate all four extremities is very difficult, both for the parents and for the surgeon. Therefore one must be absolutely sure that this management strategy is the only way to save the patient's life. Two cases of meningococcal and staphylococcal sepsis treatment are described in this paper. The surgical approach is discussed together with a review of the literature. PMID:15877261

  14. Henoch-Schonlein purpura with intestinal perforation and cerebral hemorrhage: a case report.

    PubMed

    Wang, Hong-Liang; Liu, Hai-Tao; Chen, Qi; Gao, Yang; Yu, Kai-Jiang

    2013-04-28

    Henoch-Schonlein purpura (HSP) with intestinal perforation and cerebral hemorrhage is a very rare clinical condition. There has been no report of HSP complicated with both intestinal perforation and cerebral hemorrhage until October 2012. Here we describe a case of HSP with intestinal perforation and cerebral hemorrhage in a 5-year-old girl. Plain abdominal radiograph in the erect position showed heavy gas in the right subphrenic space with an elevated diaphragm. Partial resection of the small intestine was performed, and pathological analysis suggested chronic suppurative inflammation in all layers of the ileal wall and mesentery. Seventeen days after surgery, cerebral hemorrhage developed and the patient died. PMID:23674862

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

    PubMed

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

    2015-07-01

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

  16. [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

  17. Thrombocytosis following splenectomy and aortic valve replacement for idiopathic thrombocytopaenic purpura with bicuspid aortic valve

    PubMed Central

    Katiyar, Sarika; Ganjsinghani, Payal Kamlesh; Jain, Rajnish Kumar

    2015-01-01

    Idiopathic thrombocytopaenic purpura (ITP) patients are at high risk for complications during and after cardiac surgeries involving cardiopulmonary bypass. The main clinical problem of primary ITP is an increased risk of bleeding although bleeding may not always be present. More recently, thrombosis has become appreciated as another potential complication of the procedure. We report a 22-year-old female patient with ITP with bicuspid aortic valve and splenomegaly, who underwent uncomplicated aortic valve replacement and splenectomy simultaneously. She was readmitted with chest pain due to coronary thrombosis following splenectomy which made the management difficult. We describe our experience in managing this patient who presented with thrombotic complication rather than bleeding in post-operative period and the challenges met in maintaining appropriate anticoagulation for aortic valve replacement as well as thrombosis, post-splenectomy PMID:26379295

  18. [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

  19. Disseminate intradermal bacterial colonization presenting as palpable purpura in lymphoblastic leukemia.

    PubMed

    Shelley, W B; Zolin, W D

    1983-05-01

    A patient with acute lymphoblastic leukemia suddenly developed a disseminated monomorphic eruption of purpuric papules. The papules were initially thought to be lesions of vasculitis, leukemia cutis, or septic emboli. Histologic study, however, revealed large focal colonies of gram-positive cocci within the dermis. It is postulated that a bacteremia of antibiotic-resistant cocci led to dissemination of these organisms into a virtually defenseless skin. The patient's pancytopenia and consequent immune paralysis are viewed as accounting for this focal bacterial colonization and for the remarkable absence of clinical and histologic inflammatory response. Such hematogenous noninflammatory bacterial colonization of the skin must be added to the differential diagnosis of palpable purpura. PMID:6575017

  20. 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

  1. 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

  2. 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

  3. Thrombocytosis following splenectomy and aortic valve replacement for idiopathic thrombocytopaenic purpura with bicuspid aortic valve.

    PubMed

    Katiyar, Sarika; Ganjsinghani, Payal Kamlesh; Jain, Rajnish Kumar

    2015-08-01

    Idiopathic thrombocytopaenic purpura (ITP) patients are at high risk for complications during and after cardiac surgeries involving cardiopulmonary bypass. The main clinical problem of primary ITP is an increased risk of bleeding although bleeding may not always be present. More recently, thrombosis has become appreciated as another potential complication of the procedure. We report a 22-year-old female patient with ITP with bicuspid aortic valve and splenomegaly, who underwent uncomplicated aortic valve replacement and splenectomy simultaneously. She was readmitted with chest pain due to coronary thrombosis following splenectomy which made the management difficult. We describe our experience in managing this patient who presented with thrombotic complication rather than bleeding in post-operative period and the challenges met in maintaining appropriate anticoagulation for aortic valve replacement as well as thrombosis, post-splenectomy. PMID:26379295

  4. Lifetime cost of meningococcal disease in France: Scenarios of severe meningitis and septicemia with purpura fulminans.

    PubMed

    Bénard, Stève; Wright, Claire; Voisine, Jimmy; Olivier, Catherine W; Gaudelus, Joël

    2016-01-01

    Invasive meningococcal disease (IMD) is life-threatening and can result in severe sequelae. In France, no data have been published on the costs of severe IMD cases. Two realistic scenarios were developed with national experts (clinicians and social workers): a 6-year-old child with purpura fulminans with amputation of both legs below the knee (case A) and a 3-year-old with meningitis and severe neurological sequelae (case B). Additional scenarios included other typical sequelae of IMD such as chronic kidney disease (CKD), profound deafness and epilepsy. Data on healthcare, disability, educational and other resource use were obtained from experts and families of patients with similar sequelae. Unit costs (2013) were mainly obtained from the literature and the National Health Insurance (NHI). Time horizon was based on life expectancies of patients (77 and 55 years, respectively). A 4% discount rate decreasing to 2% after 30 years was applied. Costs are presented from the perspective of the NHI, publicly funded organizations and patients' families or their private health insurances. purpura fulminans with amputations is associated with a lifelong discounted cost of €768,875. Adding CKD doubles the amount (€1,480,545). Meningitis with severe neuro-cognitive sequelae results in a lifelong discounted cost of €1,924,475. Adding profound deafness and epilepsy slightly increases the total cost (€2,267,251). The first year is the most expensive in both scenarios (€166,890 and €160,647 respectively). The main cost drivers for each scenario are prostheses and child/adult stays in healthcare facilities, respectively. Overall, patients' families or his private insurance had to pay around 13% of total cost (101,833€ and 258,817€, respectively). This study fills a gap in the body of knowledge on IMD sequelae care and lifetime costs in France. The potentially high economic burden of IMD, in addition to its physical, psychological and social burden, reinforces the need for prevention. PMID:26688376

  5. A Lower Proportion of Regulatory B Cells in Patients with Henoch–Schoenlein Purpura Nephritis

    PubMed Central

    Qu, Zhihui; Zhao, Songchen; Zhang, Li; Li, Man; Sun, Xiguang; Jiang, Yanfang

    2016-01-01

    Background Henoch—Schoenlein purpura is the one of most common types of systemic vasculitis that involves impaired renal function and Henoch-Schoenlein purpura nephritis (HSPN). The diagnosis of this condition is largely based on immunohistologic detection of immunoglobulin A1-containing immune complex in the glomerular deposits of mesangium. Despite clinical advances, the etiopathogenesis of HSPN is still largely unknown. Methods In this study, we enrolled 25 newly diagnosed HSPN patients and 14 healthy controls. Then, fractions of B cell subtypes were determined in venous blood using flow cytometry. The serum interleukin (IL)-10 concentration was determined by enzyme-linked immunosorbent assay. Results Compared to those in healthy controls, the numbers of CD38+CD19+, CD86+CD19+, CD38+CD86+CD19+, and CD95+CD19+ B cells per microliter of blood were significantly higher in HSPN patients. In contrast, the numbers of CD5+CD19+, IL-10+CD19+, CD5+CD1d+CD19+, and IL-10+CD5+CD1d+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly lower in HSPN patients. Following treatment, the numbers of CD38+CD19+ and CD86+CD19+ B cells per microliter of blood were significantly reduced in HSPN patients. However, the numbers of CD5+CD1d+CD19+, CD5+CD1d+IL-10+CD19+, and IL-10+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly increased in HSPN patients following treatment. The estimated glomerular filtration rate (eGFR) was negatively correlated with the number of CD38+CD19+ B cells but positively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration. The 24-h urinary protein concentration was positively correlated with the number of CD38+CD19+B cells but negatively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration. Conclusion Our results suggest that CD38+CD19+ and CD1d+CD5+CD19+ B cells (Bregs) contribute to the pathogenesis of HSPN. PMID:27030970

  6. 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

  7. 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.

  8. 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-Schnlein 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

  9. Cerebral Vasospasm and Intracerebral Haemorrhage in a Case of Pregnancy-Related Thrombotic Thrombocytopoenic Purpura / Haemolytic Uraemic Syndrome

    PubMed Central

    Duncan, I.C.

    2005-01-01

    Summary We report a case of a woman with pregnancyrelated thrombotic thrombocytopoenic purpura / haemolytic uraemic syndrome (TTP/HUS) who developed cerebral vasospasm similar to that seen in the other pregnancy-related thrombotic microangiopathic syndromes of eclampsia and HELLP syndrome. A further complication in this case was the development of a focal intracerebral haemorrhage necessitating surgical removal. Despite a successful evacuation of the haematoma and several plasma exchange treatments she developed recurrent haemolysis and thrombocytopoenia with an eventual fatal outcome due to severe pulmonary and gastrointestinal haemorrhage. PMID:20584498

  10. 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

  11. Henoch-Schönlein purpura complicated by acalculous cholecystitis and intussusception, and following recurrence with appendicitis.

    PubMed

    Özkaya, Ahmet Kağan; Güler, Ekrem; Çetinkaya, Ahmet; Karakaya, Ali Erdal; Göksügür, Yalçın; Katı, Ömer; Güler, Ahmet Gökhan; Davutoğlu, Mehmet

    2016-05-01

    Henoch-Schönlein purpura (HSP) is the most common childhood systemic vasculitis. Gastro-intestinal involvement occurs in two-thirds of patients. The characteristic skin lesions generally precede abdominal symptoms or present concurrently. A 7-year-old boy presented with intussusception and acalculous cholecystitis and had a cholecystectomy. Two weeks later he was re-admitted with features typical of HSP which responded to corticosteroids. Eleven months later he presented with abdominal pain and recurrence of HSP and, at laparotomy, there was acute appendicitis. This is the first case of a child presenting with HSP complicated by acalculous cholecystitis. PMID:27077617

  12. 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

  13. 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

  14. Screening of celiac disease in children with Henoch-Schoenlein purpura.

    PubMed

    Soylu, Alper; Öztürk, Yeşim; Doğan, Yavuz; Özmen, Derya; Yılmaz, Özlem; Kuyum, Pınar; Kavukçu, Salih

    2016-05-01

    Prevalence of celiac disease (CD) is 2.42 % in healthy Turkish children. The frequency of IgA-associated disorders is increased in CD. Henoch-Schoenlein purpura (HSP) is an IgA-associated vasculitis. Association of HSP with CD has not been evaluated. We aimed to evaluate whether CD prevalence is increased in children with HSP. Children with HSP were evaluated for demographic, anthropometric, clinical, and laboratory data including urinalysis, complete blood count, albumin, creatinine, and IgA levels. In addition, tTG-IgA, EMA-IgA, anti-DGP-IgA, and IgG antibody levels were measured. Seropositive patients were evaluated by endoscopic small bowel biopsy. The rate of CD seropositivity and confirmed CD in HSP patients was compared to the rate in healthy Turkish children. There were 42 children (25 male) with HSP. No patient had classical CD symptoms, but two patients had growth failure. None of them had IgA deficiency, anemia or hypoalbuminemia. Celiac serology was positive in five (12 %) children. Endoscopic evaluation was performed in four patients, and two (5 %) of them were confirmed to have CD. Prevalence of both CD seropositivity and histologically confirmed CD in children with HSP was significantly higher compared to healthy Turkish children (p < 0.001 and p = 0.019, respectively). CD seropositivity rate in children with HSP (12 %) is significantly higher than the rate in healthy children. Although the number of children with HSP is small in this preliminary study, this result suggests that celiac screening may be considered in children with HSP. PMID:26792132

  15. Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

    PubMed Central

    Veronese, F.V.; Dode, R.S.O.; Friderichs, M.; Thomé, G.G.; da Silva, D.R.; Schaefer, P.G.; Sebben, V.C.; Nicolella, A.R.; Barros, E.J.G.

    2016-01-01

    Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes. PMID:27119429

  16. 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

  17. 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

  18. Stroke in Henoch-Schönlein purpura associated with methicillin-resistant Staphylococcus aureus septicemia: report of a case and review of the literature.

    PubMed

    Temkiatvises, Kanya; Nilanont, Yongchai; Poungvarin, Niphon

    2008-08-01

    Neurological involvement in Henoch-SchOnlein purpura (HSP) such as stroke is uncommon manifestiation, particularly in association with Staphylococcus aureus (S. aureus). The authors reported a 17-year-old man who developed sudden onset of right hemiparesis while he was admitted in the hospital about his prolonged fever, palpable purpura and upper gastrointestinal bleeding. He also had evidence of MRSA septicemia before the onset of right hemiparesis. Skin biopsy was done and showed that there was leukocytoclastic vasculitis with IgA deposition. He had received completed course of antibiotics and then he was subsequently improved after steroid therapy in the next 2 weeks. Review of case reports from previous English literatures, discovered the association between MRSA infection and HSP which can cause several CNS manifestations including stroke symptoms from cerebral vasculitis. PMID:18788706

  19. A higher frequency of CD4(+)CXCR5(+) T follicular helper cells in patients with newly diagnosed Henoch-Schnlein 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-Schnlein 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

  20. 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

  1. Acquired platelet function defect

    MedlinePlus

    ... Polycythemia vera Primary thrombocythemia Thrombotic thrombocytopenic purpura Other causes include: Kidney (renal) failure Medicines such as aspirin, ibuprofen, other anti-inflammatory drugs, penicillin, phenothiazines, and prednisone (after long-term use)

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

    PubMed Central

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

    2014-01-01

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

  3. Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

    PubMed

    Mbonile, Lumuli

    2016-01-01

    Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion. PMID:27032848

  4. 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

  5. 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

  6. Prevalence and significance of the MEFV gene mutations in childhood Henoch-Schönlein purpura without FMF symptoms.

    PubMed

    Dogan, Cagla Serpil; Akman, Sema; Koyun, Mustafa; Bilgen, Turker; Comak, Elif; Gokceoglu, Arife Uslu

    2013-02-01

    Familial Mediterranean fever (FMF) has been reported more frequently in patients presenting with Henoch-Schönlein purpura (HSP) than in the general population. But, there is no clear knowledge about MEFV mutations in patients with HSP. We investigated the prevalence of MEFV mutations in children with HSP and without FMF whether these mutations have any effect on the disease course or complications. A total of 76 children with HSP who had no typical symptoms of FMF were screened for the mutations in exon 2 and exon 10 of the MEFV gene. Eleven of 76 patients (14.4 %) were heterozygous (E148Q in 5, M694V in 4, M680I in 1, E148V in 1), 5 (6.6 %) were homozygous (M694V/M694V in 4, V726A/V726A in 1), and 2 (2.6 %) were compound heterozygous (E148Q/M694V mutations in 1 and L110P/E148Q mutations in 1). Altogether, 7 patients carried 2 mutated MEFV alleles (9.2 %), which was higher than that observed in the general Turkish population (1 %). No significant differences in joint, gastrointestinal, renal involvement, or subcutaneous edema, and also acute phase reactants including leukocyte count, erythrocyte sedimentation rate, and serum C-reactive protein concentration were found between the groups. The prevalence of the two allele-MEFV mutations in patients with HSP was found higher than that of the general population. However, it seems that MEFV gene mutations may not have any effect on the clinical presentation of HSP. PMID:22451026

  7. 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.

  8. Association of the paired box 2 gene polymorphism with the susceptibility and pathogenesis of Henoch?Schnlein 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?Schnlein 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

  9. Hematologic and immunological characteristics of Henoch-Schönlein purpura in rat and rabbit models induced with ovalbumin based on type III hypersensitivity

    PubMed Central

    Li, Yanhong; Feng, Xiaochun; Huang, Lan; Zhu, Hua; Xu, Yanfeng; Sui, Xiaolong; Xu, Yuhuan; Han, Yunlin; Qin, Chuan

    2015-01-01

    Henoch-Schönlein purpura (HSP) is a common systemic vasculitis in children. Animal models of HSP are needed to better understand the mechanism of HSP. Here, we investigated hematologic and immunologic profiles in HSP rat and rabbit models. Models were established with ovalbumin (OVA) based on type III hypersensitivity. During the acute phase, the models exhibited varying degrees of cutaneous purpura, joint inflammatory response, gastrointestinal bleeding, glomerular capsule protein exudation, vascular dilatation, and increased IgA expression and immune complex deposition. Twenty four hours after antigen challenge, compared with the controls, the models showed a significantly increased white blood cell count and granulocytes count and percentage, decreased number and percentage of lymphocytes, no change in platelet concentration, significantly increased serum IL-4 and TNF-α levels, and decreased CD4+ T cell, CD4/CD8 ratio, and C3 and C4 levels. Compared with the hematologic and immunologic profiles in pediatric HSP patients, the rat and rabbit HSP models can mimic pediatric HSP characteristics. Our studies provide two useful animal models for further investigations of the pathogenesis, diagnosis, drug screening and treatment of HSP. PMID:25749457

  10. 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-Schnlein 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

  11. Henoch-Schonlein Purpura

    MedlinePlus

    ... because of the frequent failure to perform direct immunofluorescence (DIF) testing on skin biopsy and the consequent ... HSP. Figure 9. Formally known as DIF (Direct Immunofluorescence) testing. This picture shows immunofluorescence testing of a ...

  12. Progressive Pigmentary Purpura

    MedlinePlus

    ... Online Store Welcome Calendar of Events Find a Dermatology DO Osteopathic Medicine Disease Database Contributors Doctor Derm ... of Trustees Contact Us Ethics Foundation for Osteopathic Dermatology What is the FOD? Governance By-Laws Committees ...

  13. 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.

  14. Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients

    PubMed Central

    2010-01-01

    Introduction Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels. Methods In Germany, patients receiving protein C concentrate (Ceprotin®, Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this national, retrospective, multi-centered study. Results Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03). Conclusions This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial. PMID:20723255

  15. 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.

  16. Target capture and target ghosts

    NASA Astrophysics Data System (ADS)

    Auerbach, Steven P.

    1996-05-01

    Optimal detection methods for small targets rely on whitened matched filters, which convolve the measured data with the signal model, and whiten the result with the noise covariance. In real-world implementations of such filters, the noise covariance must be estimated from the data, and the resulting covariance estimate may be corrupted by presence of the target. The resulting loss in SNR is called 'target capture'. Target capture is often thought to be a problem only for bright targets. This presentation shows that target capture also arises for dim targets, leading to an SNR loss which is independent of target strength and depends on the averaging method used to estimate the noise covariance. This loss is due to a 'coherent beat' between the true noise and that portion of the estimated noise covariance due to the target. This beat leads to 'ghost targets', which diminish the target SNR by producing a negative target ghost at the target's position. A quantitative estimate of this effect will be given, and shown to agree with numerical results. The effect of averaging on SNR is also discussed for data scenes with synthetic injected targets, in cases where the noise covariance is estimated using 'no target' data. For these cases, it is shown that the so-called 'optimal' filter, which uses the true noise covariance, is actually worse than a 'sub-optimal' filter which estimates the noise from scene. This apparent contradiction is resolved by showing that the optimal filter is best if the same filter is used for many scenes, but is outperformed by a filter adapted to a specific scene.

  17. 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

  18. Sputter target

    SciTech Connect

    Gates, W.G.; Hale, G.J.

    1980-06-24

    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. 1 fig.

  19. Sputter target

    SciTech Connect

    Gates, W.G.; Hale, G.J.

    1980-06-24

    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. 8 claims.

  20. LIQUID TARGET

    DOEpatents

    Martin, M.D.; Salsig, W.W. Jr.

    1959-01-13

    A liquid handling apparatus is presented for a liquid material which is to be irradiated. The apparatus consists essentially of a reservoir for the liquid, a target element, a drain tank and a drain lock chamber. The target is in the form of a looped tube, the upper end of which is adapted to be disposed in a beam of atomic particles. The lower end of the target tube is in communication with the liquid in the reservoir and a means is provided to continuously circulate the liquid material to be irradiated through the target tube. Means to heat the reservoir tank is provided in the event that a metal is to be used as the target material. The apparatus is provided with suitable valves and shielding to provide maximum safety in operation.

  1. 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

  2. The Optimal Cut-Off Value of Neutrophil-to-Lymphocyte Ratio for Predicting Prognosis in Adult Patients with Henoch–Schönlein Purpura

    PubMed Central

    Park, Chan Hyuk; Han, Dong Soo; Jeong, Jae Yoon; Eun, Chang Soo; Yoo, Kyo-Sang; Jeon, Yong Cheol; Sohn, Joo Hyun

    2016-01-01

    Background The development of gastrointestinal (GI) bleeding and end-stage renal disease (ESRD) can be a concern in the management of Henoch–Schönlein purpura (HSP). We aimed to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is associated with the prognosis of adult patients with HSP. Methods Clinical data including the NLR of adult patients with HSP were retrospectively analyzed. Patients were classified into three groups as follows: (a) simple recovery, (b) wax & wane without GI bleeding, and (c) development of GI bleeding. The optimal cut-off value was determined using a receiver operating characteristics curve and the Youden index. Results A total of 66 adult patients were enrolled. The NLR was higher in the GI bleeding group than in the simple recovery or wax & wane group (simple recovery vs. wax & wane vs. GI bleeding; median [IQR], 2.32 [1.61–3.11] vs. 3.18 [2.16–3.71] vs. 7.52 [4.91–10.23], P<0.001). For the purpose of predicting simple recovery, the optimal cut-off value of NLR was 3.18, and the sensitivity and specificity were 74.1% and 75.0%, respectively. For predicting development of GI bleeding, the optimal cut-off value was 3.90 and the sensitivity and specificity were 87.5% and 88.6%, respectively. Conclusions The NLR is useful for predicting development of GI bleeding as well as simple recovery without symptom relapse. Two different cut-off values of NLR, 3.18 for predicting an easy recovery without symptom relapse and 3.90 for predicting GI bleeding can be used in adult patients with HSP. PMID:27073884

  3. 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

  4. 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…

  5. Target assembly

    DOEpatents

    Lewis, Richard A.

    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.

  6. 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

  7. Accelerator target

    SciTech Connect

    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.

  8. 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.

  9. Thrombocytosis following thrombocytopenia in man

    PubMed Central

    Ogston, D.; Dawson, Audrey A.

    1969-01-01

    Observations are presented on the changes in the platelet count of patients during the treatment of Addisonian pernicious anaemia with vitamin B12, of thrombocytopenic purpura with prednisone, and of malignant disease with methotrexate. In each of these clinical situations, thrombocytopenia was succeeded, after a delay of a number of days, by a phase of thrombocytosis. PMID:5392350

  10. 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

  11. A Case of Microangiopathic Hemolytic Anemia after Myxoma Excision and Mitral Valve Repair Presenting as Hemolytic Uremic Syndrome

    PubMed Central

    Park, Young Joo; Kim, Sang Pil; Shin, Ho-Jin

    2016-01-01

    Microangiopathic hemolytic anemia occurs in a diverse group of disorders, including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and prosthetic cardiac valves. Hemolytic anemia also occurs as a rare complication after mitral valve repair. In this report, we describe a case of microangiopathic hemolytic anemia following myxoma excision and mitral valve repair, which was presented as hemolytic uremic syndrome. PMID:27081450

  12. 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.

  13. 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

  14. Dermatologic adverse events in pediatric patients receiving targeted anticancer therapies: a pooled analysis

    PubMed Central

    Pratilas, Christine A.; Sibaud, Vincent; Boralevi, Franck; Lacouture, Mario E.

    2015-01-01

    BACKGROUND The dermatologic adverse events (AEs) of various molecularly targeted therapies are well-described in adult cancer patients. Little has been reported on the incidence and clinical presentation of such AEs in pediatric patients with cancer. To address this gap, we analyzed the dermatologic AEs reported across clinical trials of targeted anticancer therapies in pediatric patients. METHODS We conducted an electronic literature search (PubMed, American Society of Clinical Oncology annual meetings’ abstracts, ClinicalTrials.gov, NCI’s Pediatric Oncology Branch webpage) to identify clinical trials involving targeted anticancer therapies that reported dermatologic AEs in their safety data. Studies were limited to the pediatric population, monotherapy trials (oncology), and English language publications. RESULTS Pooled data from 19 clinical studies investigating 11 targeted anticancer agents (alemtuzumab, rituximab, imatinib, dasatinib, erlotinib, vandetanib, sorafenib, cabozantinib, pazopanib, everolimus, and temsirolimus) were analyzed. The most frequently encountered dermatologic AEs were rash (127/660; 19%), xerosis (18/100; 18%), mucositis (68/402; 17%) and pruritus (12/169; 7%). Other AEs included pigmentary abnormalities of the skin/hair (13%), hair disorders (trichomegaly, hypertrichosis, alopecia and madarosis; 14%), urticaria (7%), palmoplantar erythrodysesthesia (7%), erythema, acne, purpura, skin fissures, other ‘unknown skin changes’, exanthem, infection, flushing, telangiectasia, and photosensitivity. CONCLUSION This study describes the dermatologic manifestations of targeted anticancer therapy-related AEs in the pediatric population. Since these AEs are often associated with significant morbidity, it is imperative that pediatric oncologists be familiar with their recognition and management, to avoid unnecessary dose modifications and/or termination, and to prevent impairments in patients’ quality of life. PMID:25683226

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

    NASA Astrophysics Data System (ADS)

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

    2006-06-01

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

  16. 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.

  17. Polarized internal target apparatus

    DOEpatents

    Holt, Roy J.

    1986-01-01

    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.

  18. 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.

  19. 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.

  20. 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.

  1. Urinary myeloid IgA Fc alpha receptor (CD89) and transglutaminase-2 as new biomarkers for active IgA nephropathy and henoch-Schönlein purpura nephritis

    PubMed Central

    Moresco, Rafael N.; Speeckaert, Marijn M.; Zmonarski, Slawomir C.; Krajewska, Magdalena; Komuda-Leszek, Ewa; Perkowska-Ptasinska, Agnieszka; Gesualdo, Loreto; Rocchetti, Maria T.; Delanghe, Sigurd E.; Vanholder, Raymond; Van Biesen, Wim; Delanghe, Joris R.

    2016-01-01

    Background IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) are glomerular diseases that share a common and central pathogenic mechanism. The formation of immune complexes containing IgA1, myeloid IgA Fc alpha receptor (FcαRI/CD89) and transglutaminase-2 (TG2) is observed in both conditions. Therefore, urinary CD89 and TG2 could be potential biomarkers to identify active IgAN/HSPN. Methods In this multicenter study, 160 patients with IgAN or HSPN were enrolled. Urinary concentrations of CD89 and TG2, as well as some other biochemical parameters, were measured. Results Urinary CD89 and TG2 were lower in patients with active IgAN/HSPN compared to IgAN/HSPN patients in complete remission (P < 0.001). The CD89xTG2 formula had a high ability to discriminate active from inactive IgAN/HSPN in both situations: CD89xTG2/proteinuria ratio (AUC: 0.84, P < 0.001, sensitivity: 76%, specificity: 74%) andCD89xTG2/urinary creatinine ratio (AUC: 0.82, P < 0.001, sensitivity: 75%, specificity: 74%). Significant correlations between urinary CD89 and TG2 (r = 0.711, P < 0.001), proteinuria and urinary CD89 (r = − 0.585, P < 0.001), and proteinuria and urinary TG2 (r = − 0.620, P < 0.001) were observed. Conclusions Determination of CD89 and TG2 in urine samples can be useful to identify patients with active IgAN/HSPN. PMID:27051593

  2. Targeted therapies for cancer

    MedlinePlus

    ... nlm.nih.gov/pubmed/23589545 . Kummar S, Murgo AJ, Tomaszewski JE, Doroshow JH. Therapeutic targeting of cancer cells: ... Accessed September 15, 2015. Stegmaier K, Sellers W R. Targeted therapies in oncology. In: Orkin SH, Fisher ...

  3. 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

  4. FLIR target screening

    NASA Technical Reports Server (NTRS)

    Aggarwal, R.

    1982-01-01

    Methods for the segmentation and recognition of individual targets sensed with forward looking infrared detectors are discussed. Particular attention is given to an adaptive multi-scenario target screener.

  5. Target Heart Rates

    MedlinePlus

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

  6. 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.

  7. Antithrombin III deficiency causing postsplenectomy mesenteric venous thrombosis coincident with thrombocytopenia.

    PubMed Central

    Peters, T G; Lewis, J D; Flip, D J; Morris, L

    1977-01-01

    The most commonly recognized cause of mesenteric venous thrombosis following splenectomy is hypercoagulation secondary to reactive thrombocytosis. A case is reviewed in which hypercoagulation followed splenectomy for idiopathic thrombocytopenic purpura (ITP) in spite of persistent thrombocytopenia. Episodic mesenteric venous occlusion occurred due to antithrombin III deficiency. This hypercoagulable state may be the cause of primary acute mesenteric venous occlusive disease. Symptoms and signs suggesting thrombosis in the portal circulation demand immediate coagulation studies since even in the thrombocytopenic patient thrombotic proglems can occur. Surgical intervention is the treatment of choice for segmental small bowel ischemia; warfarin therapy is indicated when there is evidence of antithrombin III deficiency. Images Fig. 1. PMID:65157

  8. Targeted Cancer Therapies

    MedlinePlus

    ... with people), and many more are in preclinical testing (research studies with animals). How are targets for targeted cancer therapies identified? ... usually mice) with purified target proteins, causing the animals to make many ... Humanizing is necessary to prevent the human immune system from recognizing ...

  9. 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.

  10. An actionable climate target

    NASA Astrophysics Data System (ADS)

    Geden, Oliver

    2016-05-01

    The Paris Agreement introduced three mitigation targets. In the future, the main focus should not be on temperature targets such as 2 or 1.5 °C, but on the target with the greatest potential to effectively guide policy: net zero emissions.

  11. Wake Shield Target Protection

    SciTech Connect

    Valmianski, Emanuil I.; Petzoldt, Ronald W.; Alexander, Neil B.

    2003-05-15

    The heat flux from both gas convection and chamber radiation on a direct drive target must be limited to avoid target damage from excessive D-T temperature increase. One of the possibilities of protecting the target is a wake shield flying in front of the target. A shield will also reduce drag force on the target, thereby facilitating target tracking and position prediction. A Direct Simulation Monte Carlo (DSMC) code was used to calculate convection heat loads as boundary conditions input into ANSYS thermal calculations. These were used for studying the quality of target protection depending on various shapes of shields, target-shield distance, and protective properties of the shield moving relative to the target. The results show that the shield can reduce the convective heat flux by a factor of 2 to 5 depending on pressure, temperature, and velocity. The protective effect of a shield moving relative to the target is greater than the protective properties of a fixed shield. However, the protective effect of a shield moving under the drag force is not sufficient for bringing the heat load on the target down to the necessary limit. Some other ways of diminishing heat flux using a protective shield are discussed.

  12. 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.

  13. 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.

  14. 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.

  15. Nova target experiments

    SciTech Connect

    Drake, R.P.

    1985-11-01

    The Nova laser, at the Lawrence Livermore National Laboratory, provides unique opportunities for target experiments. It has unprecedented energy on target and significant flexibility. The paper presented by John Hunt described the capabilities and the status of Nova. This paper discusses plans for future experiments using Nova, and the present status of target experiments. We plan to perform high-quality physics experiments that exploit the unique capabilities of Nova. Because this is our goal, we are fielding an extensive array of well-characterized target diagnostics to measure the emissions from the target. The first section of this paper discusses the basic target diagnostics. We are also taking care to quantify the performance of the laser.

  16. 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.

  17. 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

  18. HYDROGEN ISOTOPE TARGETS

    DOEpatents

    Ashley, R.W.

    1958-08-12

    The design of targets for use in the investigation of nuclear reactions of hydrogen isotopes by bombardment with accelerated particles is described. The target con struction eomprises a backing disc of a metal selected from the group consisting of molybdenunn and tungsten, a eoating of condensed titaniunn on the dise, and a hydrogen isotope selected from the group consisting of deuterium and tritium absorbed in the coatiag. The proeess for preparing these hydrogen isotope targets is described.

  19. Integrin Targeted MR Imaging

    PubMed Central

    Tan, Mingqian; Lu, Zheng-Rong

    2011-01-01

    Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

  20. 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.

  1. 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

  2. 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.

  3. GWAS and drug targets

    PubMed Central

    2014-01-01

    Background Genome wide association studies (GWAS) have revealed a large number of links between genome variation and complex disease. Among other benefits, it is expected that these insights will lead to new therapeutic strategies, particularly the identification of new drug targets. In this paper, we evaluate the power of GWAS studies to find drug targets by examining how many existing drug targets have been directly 'rediscovered' by this technique, and the extent to which GWAS results may be leveraged by network information to discover known and new drug targets. Results We find that only a very small fraction of drug targets are directly detected in the relevant GWAS studies. We investigate two possible explanations for this observation. First, we find evidence of negative selection acting on drug target genes as a consequence of strong coupling with the disease phenotype, so reducing the incidence of SNPs linked to the disease. Second, we find that GWAS genes are substantially longer on average than drug targets and than all genes, suggesting there is a length related bias in GWAS results. In spite of the low direct relationship between drug targets and GWAS reported genes, we found these two sets of genes are closely coupled in the human protein network. As a consequence, machine-learning methods are able to recover known drug targets based on network context and the set of GWAS reported genes for the same disease. We show the approach is potentially useful for identifying drug repurposing opportunities. Conclusions Although GWA studies do not directly identify most existing drug targets, there are several reasons to expect that new targets will nevertheless be discovered using these data. Initial results on drug repurposing studies using network analysis are encouraging and suggest directions for future development. PMID:25057111

  4. 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

  5. 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.

  6. 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…

  7. Advanced Targeted Nanomedicine

    PubMed Central

    Arachchige, Mohan C M; Reshetnyak, Yana K.; Andreev, Oleg A.

    2015-01-01

    Targeted drug delivery has been the major topic in drug formulation and delivery. As nanomedicine emerges to create nano scale therapeutics and diagnostics, it is still essential to embed targeting capability to these novel systems to make them useful. Here we discuss various targeting approaches for delivery of therapeutic and diagnostic nano materials in view of search for more universal methods to target diseased tissues. Many diseases are accompanied with hypoxia and acidosis. Coating nanoparticles with pH Low Insertion Peptides (pHLIPs) increases efficiency of targeting acidic diseased tissues. It has been showing promising results to create future nanotheranostics for cancer and other diseases which are dominating in the present world. PMID:25615945

  8. Retroviral cell targeting vectors.

    PubMed

    Buchholz, C J; Stitz, J; Cichutek, K

    1999-10-01

    The availability of cell targeting vectors is an unalterable requirement for in vivo gene therapy trials. This review will describe the different strategies developed over the past few years in order to target retroviral vectors to preselected human cell types by genetic modification of the envelope (Env) proteins. Current targeting concepts include the substitution of the complete Env protein as well as the incorporation of new receptor binding domains into the Env protein. These approaches are aimed at altering the host range of vectors with a natural tropism for non-human cells to specific human cell types, or achieving tissue-specificity for vectors that would naturally infect a wide spectrum of human cell types. Targeting concepts and efficient targeting vectors with potential for clinical trials will be described, and their advantages and disadvantages will be discussed. PMID:11249668

  9. 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.

  10. Targeted delivery of nanomedicines.

    PubMed

    Kumar Khanna, Vinod

    2012-01-01

    The role of targeting of the diseased region by a drug is emphasized. The rationale for resorting to nanomaterials as drug carriers is explained. A clear understanding of the biological environment, its degradation in diseased condition, and the interaction of the drug with it in normal condition and during illness lie at the core of successful drug delivery. Passive and active drug targeting approaches are differentiated. Commonly used drug targets, targeting ligands, and nanoscale systems are elaborated. Mechanisms of internalization of nanomedicines and circumventing P-glycoprotein mediated resistance are outlined. The paper presents an overview of the current scenario of targeted transportation of nanomedicines to the affected organ and suggests future research directions. PMID:22577576

  11. 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 sequencesindicating 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

  12. Intermittent cyclophosphamide treatment of autoimmune thrombocytopenia

    PubMed Central

    Weinerman, Brian; Maxwell, Ian; Hryniuk, William

    1974-01-01

    Cyclophosphamide was given intermittently rather than daily to 14 patients with autoimmune thrombocytopenic purpura. Eight patients responded and six did not. In those who responded the rise in platelet count was rapid, and in all patients the lack of toxicity was striking. Intermittent cyclophosphamide seems effective in some cases of autoimmune thrombocytopenia and is safe, at least in the short term. Controlled trials would be required to prove that intermittent is better than daily administration. PMID:4473260

  13. Mitomycin-C-Induced TTP/HUS Treated Successfully with Rituximab: Case Report and Review of the Literature

    PubMed Central

    Yamin, Hanah; Smith, Hedy

    2013-01-01

    Microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, renal failure, and neurologic symptoms comprise the cardinal features of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Etiologies can include medications, infections, cancers, or transplantation. We present a patient with a history of rectal cancer treated with mitomycin-C who developed MAHA, acute kidney injury, and thrombocytopenia 6 months after completing therapy and to did not respond the plasmapheresis or steroids. She was treated with four weekly doses of rituximab with full recovery. PMID:23762670

  14. Is it safe to avoid bone marrow examination in suspected itp?

    PubMed

    Naithani, Rahul; Kumar, Rajat; Mahapatra, M; Agrawal, Neerja; Pati, H P; Choudhry, V P

    2007-01-01

    Two children with suspected ITP are described. One child was treated outside with corticosteroids and was diagnosed acute lymphoblastic leukemia. Another child was fresh and diagnosed as acute myeloid leukemia on bone marrow aspirate examination. Both the children had no physical or peripheral smear finding suggestive of leukemia. We suggest that a bone marrow examination is required in developing countries for evaluation of thrombocytopenia before labeling it an immune thrombocytopenic purpura. PMID:17454791

  15. The presence of precursors of benign pre-B lymphoblasts (hematogones) in the bone marrow of a paediatric patient with cytomegalovirus infection.

    PubMed

    Moreno-Madrid, F; Uberos, J; Díaz-Molina, M; Ramírez-Arredondo, A; Jiménez-Gámiz, P; Molina-Carballo, A

    2008-01-01

    Hematogones are normal B-lymphoid precursors that multiply in the bone marrow of small children and of adults with ferropenic anaemia, neuroblastoma or idiopathic thrombocytopenic purpura. They are not normally found in peripheral blood, and the immunophenotype is virtually indistinguishable from that of B lymphoblasts. We discuss the case of a 3-month infant with an active cytomegalovirus infection, with hepatitis and pancytopenia associated with 13% hematogones in the bone marrow. PMID:21892313

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. Targeting Neural Circuits.

    PubMed

    Rajasethupathy, Priyamvada; Ferenczi, Emily; Deisseroth, Karl

    2016-04-21

    Optogenetic methodology enables direct targeting of specific neural circuit elements for inhibition or excitation while spanning timescales from the acute (milliseconds) to the chronic (many days or more). Although the impact of this temporal versatility and cellular specificity has been greater for basic science than clinical research, it is natural to ask whether the dynamic patterns of neural circuit activity discovered to be causal in adaptive or maladaptive behaviors could become targets for treatment of neuropsychiatric diseases. Here, we consider the landscape of ideas related to therapeutic targeting of circuit dynamics. Specifically, we highlight optical, ultrasonic, and magnetic concepts for the targeted control of neural activity, preclinical/clinical discovery opportunities, and recently reported optogenetically guided clinical outcomes. PMID:27104976

  7. 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

  8. 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

  9. Target-detection strategies

    NASA Astrophysics Data System (ADS)

    Schachter, Bruce J.

    2013-04-01

    Hundreds of simple target-detection algorithms were tested on mid- and long-wave forward-looking infrared images. Each algorithm is briefly described. Indications are given as to which performed well. Most of these simple algorithms are loosely derived from standard tests of the difference of two populations. For target detection, these are populations of pixel grayscale values or features derived from them. The statistical tests are implemented in the form of sliding triple window filters. Several more elaborate algorithms are also described with their relative performances noted. They utilize neural networks, deformable templates, and adaptive filtering. Algorithm design issues are broadened to cover system design issues and concepts of operation. Since target detection is such a fundamental problem, it is often used as a test case for developing technology. New technology leads to innovative approaches for attacking the problem. Eight inventive paradigms, each with deep philosophical underpinnings, are described in relation to their effect on target detector design.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. SETI target selection.

    NASA Astrophysics Data System (ADS)

    Latham, D. W.; Soderblom, D. R.

    1995-06-01

    The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. The authors propose strategies for target selection with two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar-type stars, and to minimize the chances of missing signals from unexpected sites.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. The Sinuous Target

    SciTech Connect

    Zwaska, R.

    2015-06-01

    We report on the concept for a target material comprised of a multitude of interlaced wires of small dimension. This target material concept is primarily directed at high-power neutrino targets where the thermal shock is large due to small beam sizes and short durations; it also has applications to other high-power targets, particularly where the energy deposition is great or a high surface area is preferred. This approach ameliorates the problem of thermal shock by engineering a material with high strength on the micro-scale, but a very low modulus of elasticity on the meso-scale. The low modulus of elasticity is achieved by constructing the material of spring-like wire segments much smaller than the beam dimension. The intrinsic bends of the wires will allow them to absorb the strain of thermal shock with minimal stress. Furthermore, the interlaced nature of the wires provides containment of any segment that might become loose. We will discuss the progress on studies of analogue materials and fabrication techniques for sinuous target materials.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. Cooled particle accelerator target

    DOEpatents

    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.

  7. 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.

  8. 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

  9. 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.

  10. Foam encapsulated targets

    DOEpatents

    Nuckolls, John H.; Thiessen, Albert R.; Dahlbacka, Glen H.

    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.

  11. 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.

  12. 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.

  13. 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.

  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. The targets of curcumin.

    PubMed

    Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

    2011-03-01

    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-kB), 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. 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.

  17. 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

  18. Target-Rich Environment

    ERIC Educational Resources Information Center

    Perna, Mark C.

    2005-01-01

    Target marketing is defining school enrollment goals and then developing a strategic plan to accomplish those goals through the use of specific communication vehicles and community focus. It is critical to reach the right audience, with the right message, at the right time, for the right cost. In this brief article, the author describes several…

  19. Target Chamber Manipulator

    NASA Astrophysics Data System (ADS)

    Tantillo, Anthony; Watson, Matthew

    2015-11-01

    A system has been developed to allow remote actuation of sensors in a high vacuum target chamber used with a particle accelerator. Typically, sensors of various types are placed into the target chamber at specific radial and angular positions relative to the beam line and target. The chamber is then evacuated and the experiments are performed for those sensor positions. Then, the chamber is opened, the sensors are repositioned to new angles or radii, and the process is repeated, with a separate pump-down cycle for each set of sensor positions. The new sensor positioning system allows scientists to pre-set the radii of up to a dozen sensors, and then remotely actuate their angular positions without breaking the vacuum of the target chamber. This reduces the time required to reposition sensors from 6 hours to 1 minute. The sensors are placed into one of two tracks that are separately actuated using vacuum-grade stepping motors. The positions of the sensors are verified using absolute optical rotary encoders, and the positions are accurate to 0.5 degrees. The positions of the sensors are electronically recorded and time-stamped after every change. User control is through a GUI using LabVIEW.

  20. Targeted therapy in leukemia.

    PubMed

    Downing, James R

    2008-05-01

    Research conducted over the last two decades has yielded a detailed understanding of the molecular lesions that contribute to the malignant transformation of hematopoietic stem cells and committed progenitors into the various forms of acute and chronic leukemia. Although our understanding of the molecular pathology of leukemia remains incomplete, the information gained to date has had a profound impact on the way these malignancies are both diagnosed and monitored during therapy. More recently, targeted therapies have been developed against some of the identified genetic lesions. These therapies have led to significant improvements in patient outcomes while simultaneously decreasing therapy-related toxicity. With the advent of genome-wide methods to define the total complement of genetic and epigenetic lesions involved in leukemogenesis, new targeted therapies can be anticipated. This review highlights some of the targeted therapies that are presently being used to treat hematopoietic malignancies and describes some of the recent advances that should have a significant impact on the development of future target therapies. PMID:18437169

  1. 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...

  2. 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.

  3. 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

  4. Conducting Pulsed Target

    NASA Astrophysics Data System (ADS)

    Yoshimura, Koji; Yamanoi, Yutaka; Sievers, Peter; Autin, Bruno

    2005-12-01

    Conducting pulsed target scheme has been studied as an alternative targetry solution used for a dedicated high-intense and bright muon source (PRISM). We made a conceptual design and have developed a pulse power supply and a mercury loop to be used for the proof-of-principle test.

  5. Right on Target

    ERIC Educational Resources Information Center

    Henderson, Nancy

    2008-01-01

    This article features the Target Community and Educational Services program, a salaried arrangement that allows students at McDaniel College to complete their studies while living with, and managing, clients with developmental disabilities. In what is believed to be the only arrangement of its kind in the U.S., full-time graduate students agree to…

  6. 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

  7. Henoch-Schönlein Purpura

    MedlinePlus

    ... Joseph Flynn, M.D., Barbara Fivush, M.D.; Steve Wassner, M.D.; John Brandt, M.D.; Deepa ... Strategic Plans & Reports Advisory & Coordinating Committees Research Areas Jobs at NIDDK FAQs Visit Us News NIDDK News ...

  8. 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

  9. Targeted Therapies in Melanoma

    PubMed Central

    Moschos, Stergios J.; Pinnamaneni, Ramya

    2015-01-01

    Synopsis Advances in understanding the biology of melanoma have provided great insights about the mechanisms of chemoresistance and its genetic heterogeneity in parallel with advances in drug design culminating in recent major treatment breakthroughs using small molecules inhibitors in metastatic melanoma (MM). While clinical benefit of targeted therapies has been unquestionable, future advances can only be possible if we better understand the interplay between genetic aberrations and role of other crucial non-genetic changes yet to be identified by such projects as the Cancer Genome Atlas Project (TCGA) in Melanoma. Combination therapies, either among small molecule inhibitors themselves and/or with immunotherapies may be the optimal strategy to prevent development of drug resistance that is inherently linked with such targeted therapies. PMID:25769717

  10. 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

  11. 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

  12. 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

  13. Guilty Feelings, Targeted Actions

    PubMed Central

    Cryder, Cynthia E.; Springer, Stephen; Morewedge, Carey K.

    2014-01-01

    Early investigations of guilt cast it as an emotion that prompts broad reparative behaviors that help guilty individuals feel better about themselves or about their transgressions. The current investigation found support for a more recent representation of guilt as an emotion designed to identify and correct specific social offenses. Across five experiments, guilt influenced behavior in a targeted and strategic way. Guilt prompted participants to share resources more generously with others, but only did so when those others were persons whom the participant had wronged and only when those wronged individuals could notice the gesture. Rather than trigger broad reparative behaviors that remediate one’s general reputation or self-perception, guilt triggers targeted behaviors intended to remediate specific social transgressions. PMID:22337764

  14. 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

  15. Characterizing Kepler asteroseismic targets

    NASA Astrophysics Data System (ADS)

    Molenda-Żakowicz, J.; Latham, D. W.; Catanzaro, G.; Frasca, A.; Quinn, S. N.

    2011-04-01

    Stellar structure and evolution can be studied in great detail by asteroseismic methods, provided data of high precision are available. We determine the effective temperature (Teff), surface gravity (log g), metallicity and the projected rotational velocity (v sin i) of 44 Kepler asteroseismic targets using our high-resolution (R > 20 000) spectroscopic observations; these parameters will then be used to compute asteroseismic models of these stars and to interpret the Kepler light curves. We use the method of cross-correlation to measure the radial velocity (RV) of our targets, while atmospheric parameters are derived using the ROTFIT code and spectral synthesis method. We discover three double-lined spectroscopic binaries, HIP 94924, HIP 95115 and HIP 97321 - for the last system, we provide the orbital solution, and we report two suspected single-lined spectroscopic binaries, HIP 94112 and HIP 96062. For all stars from our sample we derive RV, v sin i, Teff, log g and metallicity, and for six stars, we perform a detailed abundance analysis. A spectral classification is done for 33 targets. Finally, we show that the early-type star HIP 94472 is rotating slowly (v sin i= 13 km s-1) and we confirm its classification to the Am spectral type which makes it an interesting and promising target for asteroseismic modelling. The comparison of the results reported in this paper with the information in the Kepler Input Catalogue (KIC) shows an urgent need for verification and refinement of the atmospheric parameters listed in the KIC. That refinement is crucial for making a full use of the data delivered by Kepler and can be achieved only by a detailed ground-based study. The data used in this paper have been obtained at the Catania Astrophysical Observatory (Italy), the F. L. Whipple Observatory, Arizona (USA) and the Oak Ridge Observatory, Massachusetts (USA).

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. Radiation calibration targets

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Several prominent features of Mars Pathfinder and surrounding terrain are seen in this image, taken by the Imager for Mars Pathfinder on July 4 (Sol 1), the spacecraft's first day on the Red Planet. Portions of a lander petal are at the lower part of the image. At the left, the mechanism for the high-gain antenna can be seen. The dark area along the right side of the image represents a portion of the low-gain antenna. The radiation calibration target is at the right. The calibration target is made up of a number of materials with well-characterized colors. The known colors of the calibration targets allow scientists to determine the true colors of the rocks and soils of Mars. Three bull's-eye rings provide a wide range of brightness for the camera, similar to a photographer's grayscale chart. In the middle of the bull's-eye is a 5-inch tall post that casts a shadow, which is distorted in this image due to its location with respect to the lander camera.

    A large rock is located at the near center of the image. Smaller rocks and areas of soil are strewn across the Martian terrain up to the horizon line.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C.

  1. Polarimetric laser radar target classification.

    PubMed

    Chun, Cornell S L; Sadjadi, Firooz A

    2005-07-15

    Imaging laser radar (ladar) systems have been developed for automatic target identification in surveillance systems. Ladar uses the range value at the target pixels to estimate the target's 3-D shape and identify the target. For targets in clutter and partially hidden targets, there are ambiguities in determining which pixels are on target that lead to uncertainties in determining the target's 3-D shape. An improvement is to use the polarization components of the reflected light. We describe the operation and preliminary evaluation of a polarization diverse imaging ladar system. Using a combination of intensity, range, and degree of polarization, we are better able to identify and distinguish the target from other objects of the same class. PMID:16092352

  2. 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.

  3. 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}.

  4. 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

  5. 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

  6. 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

  7. 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}.

  8. 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.

  9. Targeted therapy in gastrointestinal malignancies

    PubMed Central

    Chhatrala, Ravi; Thanavala, Yasmin; Iyer, Renuka

    2014-01-01

    Increased understanding of cancer pathogenesis has identified several pathways that serve as potential targets for novel targeted agents in development. The selection of targeted cancer therapy based on biomarkers has instigated a new era of personalized medicine and changed the way we practice oncology. Many targeted agents are approved for treatment of gastrointestinal malignancies most targeting tumor angiogenesis, and many more are in different phases of development. Here we briefly summarize nine different targeted agents that are approved currently in the U.S. and several other agents currently being studied in various gastrointestinal cancers. PMID:24737952

  10. 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

  11. 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

  12. 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.

  13. A Note on Inflation Targeting.

    ERIC Educational Resources Information Center

    Lai, Ching-chong; Chang, Juin-jen

    2001-01-01

    Presents a pedagogical graphical exposition to illustrate the stabilizing effect of price target zones. Finds that authorities' commitment to defend a price target zone affects the public's inflation expectations and, in turn, reduces actual inflation. (RLH)

  14. Solid Polarized Targets and Applications

    SciTech Connect

    Crabb, D. G.

    2008-02-06

    Examples are given of dynamically polarized targets in use today and how the subsystems have changed to meet the needs of todays experiments. Particular emphasis is placed on target materials such as ammonia and lithium deuteride. Recent polarization studies of irradiated materials such as butanol, deuterated butanol, polyethylene, and deuterated polyethylene are presented. The operation of two non-DNP target systems as well as applications of traditional DNP targets are briefly discussed.

  15. 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

  16. Successful treatment of congenital TTP with a novel approach using plasma-derived factor VIII.

    PubMed

    Naik, Swati; Mahoney, Donald H

    2013-10-01

    We describe a 19-year-old boy who was diagnosed with congenital thrombotic thrombocytopenic purpura (cTTP) at 7 months of age. He was subsequently treated with fresh frozen plasma infusions every 3 to 4 weeks for the next 15 years at which point he developed significant hypersensitivity reactions to fresh frozen plasma. He required immunosuppressive therapy with systemic desensitization in the intensive care unit but did not tolerate this regimen and suffered debilitating adverse effects. On the basis of the observations from United Kingdom, he was started on a trial with Koate, a plasma-derived factor VIII concentrate with ADAMTS-13 activity that is commercially available in the United States. He tolerated Koate without any complications and attained a target platelet count of>100,000/μL. He has now been in remission for 36 months and responds to exacerbations of cTTP with additional doses of Koate. For patients with cTTP who are intolerant to plasma infusions, therapy with select plasma-derived factor concentrates with ADAMTS-13 activity may represent a reasonable alternative therapy. PMID:23128332

  17. 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

  18. 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

  19. Profiling of miRNA expression in immune thrombocytopenia patients before and after Qishunbaolier (QSBLE) treatment.

    PubMed

    Burenbatu; Borjigin, Mandula; Eerdunduleng; Huo, Wenyan; Gong, Cuiqin; Hasengaowa; Zhang, Guiping; Longmei; Li, Ming; Zhang, Xuemei; Sun, Xiaohui; Yang, Jie; Wang, Shuanglian; Narisu, Narisu; Liu, Yangjian; Bai, Haihua

    2015-10-01

    Immune thrombocytopenia (ITP), also known as idiopathic thrombocytopenic purpura, is an autoimmune disease characterized by low platelet count and increased bleeding tendency. Currently, glucocorticoid and splenectomy are the main therapies for ITP but with obvious side effects including tendency of relapse and risk of internal bleeding. In this study, we report the Mongolian medicine Qishunbaolier (QSBLE) can significantly and efficiently increase platelet count with a low recurrent rate and unnoticeable side effect. We profiled the microRNA (miRNA) expression in the blood sample of ITP patients and identified 44 miRNAs that are differentially expressed in ITP patients before and after QSBLE treatment. Out of these 44 miRNAs, 25 are expressed in control subjects and are downregulated in ITP patients, whereas the treatment with QSBLE restores their expressions to the level of control subjects. This result suggests that abnormal expression of these 25 miRNAs might be connected to the pathogenesis of ITP. Interestingly, 14 of those 44 miNRAs are predicted to target at least once on 31 known IPT associated genes, indicating the possible mechanism of QSBLE on ITP therapy. PMID:26297543

  20. Helicobacter pylori and autoimmune diseases

    PubMed Central

    Hasni, S; Ippolito, A; Illei, GG

    2013-01-01

    Helicobacter pylori (H. pylori) is a widely prevalent microbe, with between 50 and 80% of the population infected worldwide. Clinically, infection with H. pylori is commonly associated with peptic ulcer disease, but many of those infected remain asymptomatic. H. pylori has evolved a number of means to affect the host immune response and has been implicated in many diseases mitigated by immune dysregulation, such as immune thrombocytopenic purpura (ITP), atrophic gastritis, and mucosa associated lymphoid tissue (MALT) lymphoma. Autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren’s syndrome, are the result of a dysregulated host immune system which targets otherwise healthy tissues. The exact etiology of autoimmune diseases is unclear, but it has long been suggested that exposure to certain environmental agents, such as viral and bacterial infection or chemical exposures, in genetically susceptible individuals may be the catalyst for the initiation of autoimmune processes. Because of its prevalence and ability to affect human immune function, many researchers have hypothesized that H. pylori might contribute to the development of autoimmune diseases. In this article, we review the available literature regarding the role of chronic H. pylori infection in various autoimmune disease states. PMID:21902767

  1. 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

  2. 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

  3. Split-target neutronics and the MLNSC spallation target system

    NASA Astrophysics Data System (ADS)

    Russell, G. J.; Ferguson, P. D.; Pitcher, E. J.; Court, J. D.

    1997-02-01

    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.

  4. 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.

  5. ORION laser target diagnosticsa)

    NASA Astrophysics Data System (ADS)

    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.; Wright, M. J.; Hood, B. A.; Kemshall, P.

    2012-10-01

    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.

  6. ORION laser target diagnostics.

    PubMed

    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; Wright, M J; Hood, B A; Kemshall, P

    2012-10-01

    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. PMID:23126904

  7. Target detection portal

    DOEpatents

    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.

  8. 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.

  9. Novel astrocyte targets

    PubMed Central

    Carmignoto, Giorgio; Steinhäuser, Christian

    2015-01-01

    During the last 20 years, it has been well established that a finely tuned, continuous crosstalk between neurons and astrocytes not only critically modulates physiological brain functions but also underlies many neurological diseases. In particular, this novel way of interpreting brain activity is markedly influencing our current knowledge of epilepsy, prompting a re-evaluation of old findings and guiding novel experimentation. Here, we review recent studies that have unraveled novel and unique contributions of astrocytes to the generation and spread of convulsive and nonconvulsive seizures and epileptiform activity. The emerging scenario advocates an overall framework in which a dynamic and reciprocal interplay among astrocytic and neuronal ensembles is fundamental for a fuller understanding of epilepsy. In turn, this offers novel astrocytic targets for the development of those really novel chemical entities for the control of convulsive and nonconvulsive seizures that have been acknowledged as a key priority in the management of epilepsy. PMID:24609207

  10. 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

  11. 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.

  12. Novel Therapies Targeting Endometriosis

    PubMed Central

    Osteen, Kevin G.; Bruner-Tran, Kaylon L.; Lockwood, Charles J.; Krikun, Graciela; Sokalska, Anna; Duleba, Antoni J.

    2011-01-01

    Endometriosis is an often painful disorder in which the endometrial glands and stroma grow outside the uterus. The disease affects women’s quality of life and is a common cause of infertility. In this review, we describe promising new developments in the field based on in vitro assays and rodent models, each of which has the potential to be beneficial in the treatment of this disease. We will specifically describe the role of anti-inflammatory drugs, selective estrogen, or progesterone modulators, statins, antiangiogenic agents, and the potential for targeting stem cells as likely methods to hone in and eliminate endometriosis. The most promising of these potential therapies are currently slated for further testing in both rodent and nonhuman primate trials. PMID:21693775

  13. Targeting HER2

    PubMed Central

    Wong, Karen J; Baidoo, Kwamena E; Nayak, Tapan K; Regino, Celeste AS; Garmestani, Kayhan; Brechbiel, Martin W

    2010-01-01

    The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A″-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of 111In-trastuzumab by melanoma (A375) s.c. xenografts and 111In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected 111In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of 111In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by γ-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected 111In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama. PMID:20716957

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Therapeutic targets in subependymoma.

    PubMed

    Kong, Ling-Yuan; Wei, Jun; Haider, Ali S; Liebelt, Brandon D; Ling, Xiaoyang; Conrad, Charles A; Fuller, Gregory N; Levine, Nicholas B; Priebe, Waldemar; Sawaya, Raymond; Heimberger, Amy B

    2014-12-15

    Subependymomas are usually treated with surgical resection; however, no standard, defined alternative medical therapy is recommended for patients who are not surgical candidates, owing to a paucity of molecular, immunological, and genetic characterization. To address this, an ex vivo functional analysis of the immune microenvironment in subependymoma was conducted, a subependymoma cytokine/chemokine microarray was constructed for the evaluation of operational immune and molecular pathways, and a subependymoma cell line was derived and used to test a variety of cytotoxic agents that target operational pathways identified in subependymoma. We found that immune effectors are detectable within the microenvironment of subependymoma; however, marked immune suppression is not observed. The subependymoma tissue microarrays demonstrated tumor expression of p53, MDM2, HIF-1α, topoisomerase II-β, p-STAT3, and nucleolin, but not EGFRvIII, EphA2, IL-13RA2, CMV, CTLA-4, FoxP3, PD-1, PD-L1, EGFR, PDGF-α, PDGF-β, PDGFR-α, PDGFR-β, PTEN, IGFBP2, PI3K, MDM4, IDH1, mTOR, or Jak2. A topoisomerase inhibitor (WP744, IC50=0.83 μM) and a p-STAT3/HIF-1α inhibitor (WP1066, IC50=3.15 μM) demonstrated a growth inhibition of the subependymoma cell proliferation. Cumulatively, these data suggest that those agents that interfere with oncogenes operational in subependymoma may have clinical impact. PMID:25465288

  20. 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

  1. [Target volume margins for lung cancer: internal target volume/clinical target volume].

    PubMed

    Jouin, A; Pourel, N

    2013-10-01

    The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. PMID:23988437

  2. Targeted chemical nucleases

    SciTech Connect

    Sigman, D.S.; Bruice, T.W.; Mazumder, A.; Sutton, C.L. )

    1993-03-01

    The design of functional molecules has been an active area of research in chemistry and molecular biology during the past decade, encompassing topics such as host-guest chemistry, ribozymes, catalytic antibodies, and most recently, fullerenes. Nucleolytic agents that cleave the phosphodiester backbone of DNA and RNA have been another important focus of activity. Interest in this subject has paralleled, and relied on, rapid advances in molecular biology, genome mapping and sequencing, and also the chemical synthesis of deoxyoligonucleotides and peptides. The goals of this research, the methodological approaches, and the insights into chemical biology provided by these molecules are the topic of this Account, which emphasizes research with the chemical nuclease activity of 1,10-phenanthroline-copper by the authors laboratory and others but also summarizes the innovative studies of Dervan and colleagues using ferrous-EDTA linked to targeting molecules. Chemical nucleases are defined here as redox active coordination complexes that cleave DNA by an oxidative pathway. The term nuclease is used as a shorthand for nucleolytic activity. Since these reagents are generally used in excess of their substrates and also self-destruct because they generate reactive intermediates, turnover has not been rigorously demonstrated. In addition to 1,10-phenanthroline-copper and ferrous-EDTA, other chelates capable of cleaving the phosphodiester backbone of DNA under physiological conditions include metalloporphyrins, uranyl acetate, and octahedral rhodium complexes. The generation of piperidine sensitive cleavage sites resulting from guanosine oxidation has been achieved with ruthenium and nickel complexes. Chemical methods for cleaving the phosphodiester backbone by hydrolysis or nucleophilic catalysis are not yet efficient enough to be useful. 101 refs., 6 figs.

  3. Target repurposing for neglected diseases

    PubMed Central

    Pollastri, Michael P; Campbell, Robert K

    2011-01-01

    Infectious diseases are an enormous burden to global health and since drug discovery is costly, those infectious diseases that affect the developing world are often not pursued by commercial drug-discovery efforts. Therefore, pragmatic means by which new therapeutics can be discovered are needed. One such approach is target repurposing, where pathogen targets are matched with homologous human targets that have been pursued for drug discovery for other indications. In many cases, the medicinal chemistry, structural biology and biochemistry knowledge around these human targets can be directly repurposed to launch and accelerate new drug-discovery efforts against the pathogen targets. This article describes the overarching strategy of target repurposing as a tool for initiating and prosecuting neglected disease drug-discovery programs, highlighting this approach with three case studies. PMID:21859304

  4. 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.

  5. Inertial-confinement-fusion targets

    SciTech Connect

    Hendricks, C.D.

    1981-11-16

    Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques have been devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

  6. Data Mining for Target Marketing

    NASA Astrophysics Data System (ADS)

    Levin, Nissan; Zahavi, Jacob

    Targeting is the core of marketing management. It is concerned with offering the right product/service to the customer at the right time and using the proper channel. In this chapter we discuss how Data Mining modeling and analysis can support targeting applications. We focus on three types of targeting models: continuous-choice models, discrete-choice models and in-market timing models, discussing alternative modeling for each application and decision making. We also discuss a range of pitfalls that one needs to be aware of in implementing a data mining solution for a targeting problem.

  7. Guidance system for laser targets

    DOEpatents

    Porter, Gary D.; Bogdanoff, Anatoly

    1978-01-01

    A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

  8. Targets and Secondary Beam Extraction

    NASA Astrophysics Data System (ADS)

    Noah, Etam

    2014-02-01

    Several applications make use of secondary beams of particles generated by the interaction of a primary beam of particles with a target. Spallation neutrons, bremsstrahlung photon-produced neutrons, radioactive ions and neutrinos are available to users at state-of-the-art facilities worldwide. Plans for even higher secondary beam intensities place severe constraints on the design of targets. This article reports on the main targetry challenges and highlights a variety of solutions for targetry and secondary beam extraction. Issues related to target station layout, instrumentation at the beam-target interface, safety and radioprotection are also discussed.

  9. 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

  10. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia.

    PubMed

    Briggs, Carol; Kunka, Stefan; Hart, Dan; Oguni, Shinichiro; Machin, Samuel J

    2004-07-01

    A new automated method to reliably quantify reticulated platelets, expressed as the immature platelet fraction (IPF), has been developed utilizing the XE-2100 blood cell counter with upgraded software (Sysmex, Kobe, Japan). The IPF is identified by flow cytometry techniques and the use of a nucleic acid specific dye in the reticulocyte/optical platelet channel. The clinical utility of this parameter was established in the laboratory diagnosis of thrombocytopenia due to increased peripheral platelet destruction, particularly autoimmune thrombocytopenic purpura (AITP) and thrombotic thrombocytopenic purpura (TTP). Reproducibility and stability results over 48 h were good. An IPF reference range in healthy individuals was established as 1.1-6.1%, with a mean of 3.4%. Patients in whom platelet destruction might be abnormal, were studied and two of these patients followed serially during the course of treatment. The IPF was raised in several disease states. The most significant increases in IPF values were found in patients with AITP (mean 22.3%, range 9.2-33.1%) and acute TTP (mean 17.2%, range 11.2-30.9%). Following patients during treatment demonstrated that as the platelet count recovered the IPF% fell. These results show that a rapid, inexpensive automated method for measuring the IPF% is feasible and should become a standard parameter in evaluating the thrombocytopenic patient. PMID:15198738

  11. 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.

  12. Visual motion shifts saccade targets.

    PubMed

    Kosovicheva, Anna A; Wolfe, Benjamin A; Whitney, David

    2014-08-01

    Saccades are made thousands of times a day and are the principal means of localizing objects in our environment. However, the saccade system faces the challenge of accurately localizing objects as they are constantly moving relative to the eye and head. Any delays in processing could cause errors in saccadic localization. To compensate for these delays, the saccade system might use one or more sources of information to predict future target locations, including changes in position of the object over time, or its motion. Another possibility is that motion influences the represented position of the object for saccadic targeting, without requiring an actual change in target position. We tested whether the saccade system can use motion-induced position shifts to update the represented spatial location of a saccade target, by using static drifting Gabor patches with either a soft or a hard aperture as saccade targets. In both conditions, the aperture always remained at a fixed retinal location. The soft aperture Gabor patch resulted in an illusory position shift, whereas the hard aperture stimulus maintained the motion signals but resulted in a smaller illusory position shift. Thus, motion energy and target location were equated, but a position shift was generated in only one condition. We measured saccadic localization of these targets and found that saccades were indeed shifted, but only with a soft-aperture Gabor patch. Our results suggest that motion shifts the programmed locations of saccade targets, and this remapped location guides saccadic localization. PMID:24888754

  13. Targeted Training: An Integrated Initiative.

    ERIC Educational Resources Information Center

    Valvasori, Joe

    The Learning Enrichment Foundation (LEF) in Toronto, Ontario (Canada) offers 12 targeted training programs that have successfully helped "hard-to-serve" clients return to the workforce. Compared with traditional training, targeted training has a much narrower focus and adapts quickly to industry trends to meet employers' changing demands. LEF's…

  14. Targeting ion transport in cancer

    PubMed Central

    Oosterwijk, E.; Gillies, R. J.

    2014-01-01

    The metabolism of cancer cells differs substantially from normal cells, including ion transport. Although this phenomenon has been long recognized, ion transporters have not been viewed as suitable therapeutic targets. However, the acidic pH values present in tumours which are well outside of normal limits are now becoming recognized as an important therapeutic target. Carbonic anhydrase IX (CAIX) is fundamental to tumour pH regulation. CAIX is commonly expressed in cancer, but lowly expressed in normal tissues and that presents an attractive target. Here, we discuss the possibilities of exploiting the acidic, hypoxic tumour environment as possible target for therapy. Additionally, clinical experience with CAIX targeting in cancer patients is discussed. PMID:24493755

  15. TARGETING POLYMER THERAPEUTICS TO BONE

    PubMed Central

    Low, Stewart; Kopeček, Jindřich

    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

  16. 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.

  17. 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 tomographybased 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 cancertargeted 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

  18. 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.

  19. Aided targeting system simulation evaluation

    NASA Astrophysics Data System (ADS)

    Demaio, Joe; Becker, Curtis

    1994-07-01

    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.

  20. Target animacy influences chimpanzee handedness.

    PubMed

    Forrester, Gillian S; Quaresmini, Caterina; Leavens, David A; Spiezio, Caterina; Vallortigara, Giorgio

    2012-11-01

    We employed a bottom-up, quantitative method to investigate great ape handedness. Our previous investigation of gorillas (Gorilla gorilla gorilla) demonstrated that contextual information influenced an individual's handedness toward target objects. Specifically, we found a significant right-hand bias for unimanual actions directed toward inanimate target objects but not for actions directed to animate target objects (Forrester et al. in Anim Cogn 14(6):903-907, 2011). Using the identical methodological technique, we investigated the spontaneous hand actions of nine captive chimpanzees (Pan troglodytes) during naturalistic, spontaneous behavior. We assessed both the frequencies and proportions of lateralized hand actions directed toward animate and inanimate targets employing focal follow video sampling. Like the gorillas, the chimpanzees demonstrated a right-handed bias for actions directed toward inanimate targets, but not toward animate targets. This pattern was evident at the group level and for the majority of subjects at the individual level. We postulate that a right-hand bias for only inanimate targets reflects the left hemisphere's dominant neural processing capabilities for objects that have functional properties (inanimate objects). We further speculate that a population-level right-hand bias is not a human-unique characteristic, but one that was inherited from a common human-ape ancestor. PMID:22829099

  1. 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.

  2. 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

  3. Guidance and targeting for the strategic target system

    NASA Astrophysics Data System (ADS)

    White, John E.

    1989-11-01

    Guidance algorithms and targeting procedures for the Strategic Target System (STARS) launch vehicle are described. The STARS vehicle is a three stage booster, based partly upon retired Polaris A3 missile assets, which is intended to support development and testing of the Strategic Defense Initiative by delivering target payloads to the vicinity of the Kwajalein Atoll. STARS will be launched from the Kauai Test Facility located on Kauai, Hawaii. The STARS guidance objective is to deliver payloads to a prescribed target location with maximum accuracy at inter-continental ballistic missile velocities. The guidance problem is complicated by the fact that all three stages lack thrust termination or other velocity control mechanisms, and by range safety requirements for one or more out-of-plane turns. Mission objectives are achieved with a combination of guidance algorithms. The original Polaris guidance is used during the atmospheric ascent phase. The powered-explicit-guidance used by the Space Shuttle is later employed to execute an out-of-plane turn and to place the third stage as closely as possible into the desired coast trajectory. Third stage targeting is a modified Lambert procedure formulated to eliminate the target miss due to off-nominal ascent phase performance. Active guidance is also used during the third stage burn to maximize the delivery accuracy.

  4. Targeting the p53 pathway.

    PubMed

    Golubovskaya, Vita M; Cance, William G

    2013-10-01

    This article summarizes data on translational studies to target the p53 pathway in cancer. It describes the functions of the p53 and Mdm-2 signaling pathways, and discusses current therapeutic approaches to target p53 pathways, including reactivation of p53. In addition, direct interaction and colocalization of the p53 and focal adhesion kinase proteins in cancer cells have been demonstrated, and different approaches to target this interaction are reviewed. This is a broad review of p53 function as it relates to the diagnosis and treatment of a wide range of cancers. PMID:24012397

  5. 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.

  6. 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

  7. Sparsity inspired automatic target recognition

    NASA Astrophysics Data System (ADS)

    Patel, Vishal M.; Nasrabadi, Nasser M.; Chellappa, Rama

    2010-04-01

    In this paper, we develop a framework for using only the needed data for automatic target recognition (ATR) algorithms using the recently developed theory of sparse representations and compressive sensing (CS). We show how sparsity can be helpful for efficient utilization of data, with the possibility of developing real-time, robust target classification. We verify the efficacy of the proposed algorithm in terms of the recognition rate on the well known Comanche forward-looking infrared (FLIR) data set consisting of ten different military targets at different orientations.

  8. Mycothiol: a promising antitubercular target.

    PubMed

    Nilewar, S S; Kathiravan, M K

    2014-02-01

    Tuberculosis (TB) is the world's second commonest cause of death next to HIV/AIDS. The increasing emergence of multi drug resistance and the recalcitrant nature of persistent infections pose an additional challenge for the treatment of TB. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat M. tuberculosis. One such target is Mycothiol (MSH), a major low molecular-mass thiol in mycobacteria, an important cellular anti-oxidant. MSH is present only in actinomycetes and hence is a good target. This review explores mycothiol as a potential target against tuberculosis and various research ongoing worldwide. PMID:24368170

  9. 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.

  10. 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.

  11. Targeting ubiquitination for cancer therapies.

    PubMed

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

    2015-01-01

    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

  12. [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

  13. Targeting the Teaching of Theory.

    ERIC Educational Resources Information Center

    Walton, Charles W.

    1981-01-01

    Suggests that six target areas in the teaching of theory and musicianship need more attention and emphasis: listening, analysis, music reading, creativity, music writing, and keyboard harmony. Discusses content and sequence in music theory and presents two sample applications. (SJL)

  14. Strategically targeting MYC in cancer

    PubMed Central

    Posternak, Valeriya; Cole, Michael D.

    2016-01-01

    MYC is a major driver of cancer cell growth and mediates a transcriptional program spanning cell growth, the cell cycle, metabolism, and cell survival. Many efforts have been made to deliberately target MYC for cancer therapy. A variety of compounds have been generated to inhibit MYC function or stability, either directly or indirectly. The most direct inhibitors target the interaction between MYC and MAX, which is required for DNA binding. Unfortunately, these compounds do not have the desired pharmacokinetics and pharmacodynamics for in vivo application. Recent studies report the indirect inhibition of MYC through the development of two compounds, JQ1 and THZ1, which target factors involved in unique stages of transcription. These compounds appear to have significant therapeutic value for cancers with high levels of MYC, although some effects are MYC-independent. These approaches serve as a foundation for developing novel compounds to pharmacologically target MYC-driven cancers. PMID:27081479

  15. Gene targeting with retroviral vectors

    SciTech Connect

    Ellis, J.; Bernstein, A. )

    1989-04-01

    The authors have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. Stable neo gene correction events were selected at a frequency of approximately 1 G418/sup r/ cell per 3 x 10/sup 6/ infected cells. Analysis of the functional neo gene in independent targeted cell clones indicated that unintegrated retroviral linear DNA recombined with the target by gene conversion for variable distances into regions of nonhomology. In addition, transient neo gene correction events which were associated with the complete loss of the chromosomal target sequences were observed. These results demonstrated that retroviral vectors can recombine with homologous chromosomal sequences in rodent and human cells.

  16. 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.

  17. "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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  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. Chemical Structural Novelty: On-Targets and Off-Targets

    PubMed Central

    Yera, Emmanuel R.; Cleves, Ann. E.; Jain, Ajay N.

    2011-01-01

    Drug structures may be quantitatively compared based on 2D topological structural considerations and based on 3D characteristics directly related to binding. A framework for combining multiple similarity computations is presented along with its systematic application to 358 drugs with overlapping pharmacology. Given a new molecule along with a set of molecules sharing some biological effect, a single score based on comparison to the known set is produced, reflecting either 2D similarity, 3D similarity, or their combination. For prediction of primary targets, the benefit of 3D over 2D was relatively small, but for prediction of off-targets, the added benefit was large. In addition to assessing prediction, the relationship between chemical similarity and pharmacological novelty was studied. Drug pairs that shared high 3D similarity but low 2D similarity (i.e. a novel scaffold) were shown to be much more likely to exhibit pharmacologically relevant differences in terms of specific protein target modulation. PMID:21916467

  15. Protein domains as irradiation targets

    SciTech Connect

    Solomonson, L.P.; Ness, G.C.; Eichler, D.C.; McCreery, M.J.

    1986-05-01

    Recently, the authors demonstrated by radiation inactivation analysis that the target sizes for the partial activities of nitrate reductase were considerably less than that of the 100 kDa subunit. Immunoblotting analysis of NR irradiated in the presence of a free radical scavenging system (FRSS) consisting of 50mM each of mannitol and benzoic acid revealed formation of distinct bands at 90, 75, and 40 kDa with increasing doses of irradiation rather than complete destruction of the polypeptide chain. To further explore the possibility that domains may serve as irradiation targets, DNA polymerase I was selected as a model protein since the polymerase and 5'-3' exonuclease activities reside on distinct segments of the 109 kDa polypeptide chain. In the absence of the FRSS, the target sizes for the polymerase and 5'-3' exonuclease activities were 194 and 102 kDa, respectively. In the presence of FRSS the target sizes were reduced to 29 and 19 kDa, respectively. Thus, target sizes of these two activities of Pol I are substantially different and in the presence of FRSS probably represent minimal sizes of the respective functional domains.

  16. 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

  17. Molecular targets underlying general anaesthesia

    PubMed Central

    Franks, Nicholas P

    2006-01-01

    The discovery of general anaesthesia, over 150 years ago, revolutionised medicine. The ability to render a patient unconscious and insensible to pain made modern surgery possible and general anaesthetics have become both indispensible as well as one of the most widely used class of drugs. Their extraordinary chemical diversity, ranging from simple chemically inert gases to complex barbiturates, has baffled pharmacologists, and ideas about how they might work have been equally diverse. Until relatively recently, thinking was dominated by the notion that anaesthetics acted ‘nonspecifically' by dissolving in the lipid bilayer portions of nerve membranes. While this simple idea could account for the chemical diversity of general anaesthetics, it has proven to be false and it is now generally accepted that anaesthetics act by binding directly to sensitive target proteins. For certain intravenous anaesthetics, such as propofol and etomidate, the target has been identified as the GABAA receptor, with particular subunits playing a crucial role. For the less potent inhalational agents, the picture is less clear, although a relatively small number of targets have been identified as being the most likely candidates. In this review, I will describe the work that led up to the identification of the GABAA receptor as the key target for etomidate and propofol and contrast this with current progress that has been made in identifying the relevant targets for other anaesthetics, particularly the inhalational agents. PMID:16402123

  18. 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

  19. Targeting cancer with kinase inhibitors

    PubMed Central

    Gross, Stefan; Rahal, Rami; Stransky, Nicolas; Lengauer, Christoph; Hoeflich, Klaus P.

    2015-01-01

    Kinase inhibitors have played an increasingly prominent role in the treatment of cancer and other diseases. Currently, more than 25 oncology drugs that target kinases have been approved, and numerous additional therapeutics are in various stages of clinical evaluation. In this Review, we provide an in-depth analysis of activation mechanisms for kinases in cancer, highlight recent successes in drug discovery, and demonstrate the clinical impact of selective kinase inhibitors. We also describe the substantial progress that has been made in designing next-generation inhibitors to circumvent on-target resistance mechanisms, as well as ongoing strategies for combining kinase inhibitors in the clinic. Last, there are numerous prospects for the discovery of novel kinase targets, and we explore cancer immunotherapy as a new and promising research area for studying kinase biology. PMID:25932675

  20. Targeted drug therapies and cancer.

    PubMed

    Yim, K L; Cunningham, D

    2011-01-01

    With the progress of research in molecular biology and greater understanding of cell signalling systems emerge an increasing array of potential targets for the therapy of cancer. While traditional chemotherapy aims to elicit tumour cell death, it also produces undesirable side effects on physiologically proliferating cells. By isolating cell surface receptors which link specific intracellular secondary messenger pathways, researchers are increasingly able to define the biological network which drives cellular function. Of importance are routes involved in malignant transformation, proliferation, survival and angiogenesis. Thus targeted therapy is directed to specific differential growth processes particular to malignant tumours. The principle mode of action generally involves the "lock-and-key" mechanism and identifying the "Achilles' heel" for drug action. Various targeted agents have been studied and many have translated into significant clinical benefit. This chapter will describe some examples which illustrate the role of this approach in gastrointestinal cancers. PMID:21822826